Pharmacology Study Notes: Colon : COLON SPECIFIC DRUG DELIVERY SYSTEM PDF

Pharmacology Study Notes Colon COLON SPECIFIC DRUG DELIVERY SYSTEM

Pharmacology Study Notes: Colon : COLON SPECIFIC DRUG DELIVERY SYSTEM

 

FACTORS TO BE CONSIDERED IN THE DESIGN OF COLON SPECIFIC DRUG DELIVERY SYSTEM

To reach the colon and to be able to specifically deliver and absorb the drug there, the dosage forms must be formulated taking into account the obstacles of the gastrointestinal tract. The various strategies developed to achieve this goal have used the specific characteristics of this organ, i.e. transit time, pH, microflora, enzymes, disease and the colonic environment. Nevertheless, these parameters can vary from one individual to the next and also according to the pathological condition and diet.

 

Physiological Factors

Gastrointestinal transit

Gastrointestinal transit time is important for nearly all orally targeting delivery systems. The drug delivery systems first enter in to stomach and small intestine via mouth and then reach colon. In fasted state, the motility proceeds through four phases occurring in stomach and small intestine that span over a period of 2-3 h. Phase I is a quiescent period of 40-60 min, Phase II consists of intermittent contractions for a period of 40-60 min. Phase III is a period of intense contractions sweeping material out of the stomach and down the small intestine followed by Phase IV with contractions dissipating. The feeding state affects the normal pattern by irregular contractile activity.  

It has been well documented that gastric emptying varies with different types of dosage forms. Examples of gastric residence times of single-unit tablets are given in Table 1 (Abrahamsson, 1993). It has been generally accepted that liquid emptying follows a monoexponential process and digestible solids empty in a linear fashion with time.

 

Small intestinal transit

Normally, transit times through the small intestine generally found to be 3-4 h. Liquids, small solids (beads, small tablets), and larger capsule-sized units moved essentially at the same rates and the transit is unaffected by food status (Davis, 1986). In a more recent study concerning dosing in relation to the timing of food intake, found that although SIT is relatively independent of food and dosage form, it was actually shortened significantly if the dose is given 30 min before food intake. This can have adverse impact on the in vivo performance of the dosage forms.

 

Colonic Transit

In the stomach and small intestine, food residue and endogenous secretions are exposed to an essentially sterile environment through which their transit can be measured by hours. On entering the large intestine, dosage forms encounter a rich bacterial flora and transit through the large intestine can be as long as several days. It was reported that overall mean transit time is 36 h with a range of 1 to 72 h and that the transit of liquids and small solids is equal (Phillips., 1993). Thus, absorption from colon may be incomplete and erratic depending on the dose and physicochemical properties of a particular drug. In general, absorption of an insoluble drug with high dose or a drug with limited permeability is unfavorable in this region because of the limited volume of fluid available for dissolution and the significantly reduced surface area.

 Pharmacology Study Notes Colon COLON SPECIFIC DRUG DELIVERY SYSTEM pdf Pharmacology Study Notes Colon COLON SPECIFIC DRUG DELIVERY SYSTEM Pharmacology Study Notes Colon COLON SPECIFIC DRUG DELIVERY SYSTEM

Table 1. Gastrointestinal transit times for felodipine CR hydrophilic matrix

section Gastric emptying (h) Small intestine transit (h) Colon arrival (h)
Fasting Fed Fasting Fed Fasting Fed
Mean 0.6 3.2 4.7 5.1 5.3 8.3
Range 0.1-1.1 1.9-4.8 3.9-5.9 2.2-7.7 4.0-7.0 6.0-11.0
P <0.001 >0.05 >0.01

 

 

 

pH in the Colon

The pH gradient in the GIT is not in an increased order and is subjected to both inter- and intra-subject variations. In stomach the pH is 1.5 – 2.0 and 2 – 6 in fasted and fed conditions, respectively. The acidic pH is responsible for the degradation of various pH sensitive drugs and enteric coating may prevent it. In small intestine, the pH increases slightly from 6.6 – 7.5. On entry into the colon, the pH dropped to 6.4 in right colon. The pH of mid colon was found to be 6.6 and in the left colon, 7.0 (Evans et al., 1988).

Colonic pH has been shown reduced in disease state. The mean pH in a group of 7 patients with untreated ulcerative colitis was 4.7 whereas in 5 patients receiving treatment it was 5.5 (Raimundo et al., 1992).

Colonic microflora

The human colon is a dynamic and ecologically diverse environment, containing over 400 distinct species of bacteria with a population of 1011 to 1012 CFU/mL (Cummings et al., 1991), with Bacteroides, Bifidobacterium, Eubacterium, Lactobacillus, etc greatly outnumbering other species. For example, it was reported that Bacteroides, Bifidobacterium and Eubacterium could constitute as much as over 60% of the total cultivable flora (Salyers, 1984). These bacteria produce a wide spectrum of enzymes that, being reductive and hydrolytic in nature, are actively involved in many processes in the colon, such as carbohydrate and protein fermentation, bile acid and steroid transformation, metabolism of xenobiotic substances, as well as the activation and destruction of potential mutagenic metabolites. Nitroreductase, azoreductase, N-oxide and sulfoxide reductase are the most extensively investigated reductive enzymes, while glucosidase and glucuronidase are the most extensively studied hydrolytic enzymes. The primary source of nutrition for these anaerobic bacteria is carbohydrates such as non-starch polysaccharides (i.e., dietary fibers) from the intestinal chime. It is well established that non-starch polysaccharides are fermented during transit through the colon and the breakdown in the stomach and small intestine is negligible. Enzymes responsible for the degradation of polysaccharides include α-L-arabinofuranosidase, β-D-fucosidase,  β-D-

galactosidase, β-Dglucosidase, β-xylosidase, with the last three enzymes being the most active (Englyst et al., 1987). Additionally, the composition of colonic bacteria and corresponding enzymes can be influenced by many factors, including age, diet, diseases, medication such as antibiotics, and geographic regions (Mueller et al., 2006). A unique feature of colon microflora is that the growth and activity of certain specific species, most notably bifidobacteria and lactobacilli, can be selectively stimulated by nondigestible oligosaccharides which are known as prebiotics. Similar bacteriological data were observed in the rats fed with indigestible oligosaccharides where the caecal bifidobacteria population was higher than in the controls (Campbell et al., 1997).

Volume of the ascending colon

Up to 1,500 g of liquids and undigested materials (dietary fibers, resistant starch, partially degraded polysaccharides proteins, mucins, exfoliated epithelial cells, etc.) enters colon per day, which act as the substrates for microflora fermentation. Water together with the products of the fermentation and other nutrients was efficiently absorbed in the colon, condensing the contents into feces through the transit in the colon for eventual defecation. Therefore, it is very likely that the ascending colon contains the largest quantity of liquid. It would be expected that the low water–high gas environment of the transverse colon limits dissolution of materials.  The moisture content of caecal contents is believed to be about 86% (Cummings and Macfarlane, 1991). The volume of the ascending colon was measured in healthy subjects using a single photon emission computed tomography (SPECT) by acquiring the imaging of the ascending colon filled with 99Tcm-labelled Amberlite pellets, and was found to be 170±40 ml (Badley., 1993). If the moisture content in the ascending colon is approximately comparable to that of caecal contents, the quantity of fluid in the ascending colon should be 146±34 ml.

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Pharmaceutics notes B Pharmacy M pharmacy Study Material

Disease and the Colonic Environment

General intestinal diseases such as inflammatory bowel disease, Crohn’s disease, constipation and diarrhea may affect the release and absorption of colon specific drug delivery systems. All the specific approaches so far mentioned rely on the concept that enzymes produced by colonic microflora provide the trigger for specific delivery of fermentable coatings, anti-inflammatory azobond drugs, and other prodrugs to the cecum. Carrette and co-workers (1995) demonstrated that in patients with active Crohn’s disease, the metabolic activity of digestive flora (assessed on the activity of fecal glycosidases) was decreased. Azoreductase activity in feces of 14 patients with active Crohn’s disease was 20% of that of healthy subjects and similarly, beta-D-glucosidase and beta-D-glucuronidase activities in fecal homogenates incubated under anaerobic conditions were also decreased in patients. These data probably reflect large-bowel hypermotility and the associated diarrhea, leading to lower bacterial mass in the colon and might contribute to the therapeutic failure of targeting mechanisms in active ileocolic and colic Crohn’s disease.

 

[DOC Pdf PPT] Colon – ANOTOMY & PHYSIOLOGY OF COLON Functions Pharmacology Notes

Colon ANOTOMY PHYSIOLOGY OF COLON Functions Pharmacology Notes PDF ppt

Here is best notes for our readers to understand the concept of anatomy of Colon to study in depth of its physiology. Colon – ANOTOMY & PHYSIOLOGY OF COLON Functions Pharmacology Notes

The GI tract is divided into stomach, small intestine and large intestine. The large intestine extending from the ileocaecal junction to the anus is divided into three main parts. These are the colon, the rectum and the anal canal. The location of the parts of the colon is either in the abdominal cavity or behind it in the retroperitoneum. The colon itself is made up of the caecum, the ascending colon, the hepatic flexure, the transverse colon, the splenic flexure, the descending colon and the sigmoid colon (Figure 1). It is about 1.5 m long, the transverse colon being the longest and most mobile part (Meschan, 1975), and has a average diameter of about 6.5 cm. The colon from the cecum to the splenic flexure (the junction between the transverse and descending colon) is also known as the right colon. The remainder is known as the left colon.

      Arterial supply to the colon of humans comes from branches of the superior and inferior mesenteric arteries. Venous drainage usually mirrors colonic arterial supply, with the inferior mesenteric vein draining into the splenic vein, and the superior mesenteric vein joining the splenic vein to form the portal vein, which then enters the liver.

       Lymphatic drainage from the entire colon and proximal two-thirds of the rectum is to the paraortic nodes, which then drain into the cisterna chyli. The lymph from the remaining rectum and anus can either follow the same route, or drain to the internal illiac and superficial inguinal nodes. The dentate line only roughly marks this transition.  

ANOTOMY & PHYSIOLOGY OF COLON

 Figure 1.  Main features of the colon

Colon – ANOTOMY AND PHYSIOLOGY OF COLON Functions Pharmacology Notes PDF DOC Colon – ANOTOMY AND PHYSIOLOGY OF COLON Functions Pharmacology Notes PPT Colon ANOTOMY PHYSIOLOGY OF COLON Functions Pharmacology Notes PDF ppt

Functions of Colon

The colon serves four major functions. They are

  1. Creation of suitable environment for the growth of colonic microorganisms
  2. Storage reservoir of faecal contents
  3. Expulsion of the contents of the colon at an appropriate time and
  4. Absorption of potassium and bicarbonate.

 

B Pharmacy M pharmacy Study Material Pharmacology Notes PDF DRUGS SUITABLE FOR COLONIC DRUG DELIVERY

B Pharmacy M pharmacy Study Material Pharmacology Notes DRUGS SUITABLE FOR COLONIC DRUG DELIVERY

B Pharmacy M pharmacy Study Material Pharmacology Notes is an article with detailed notes on DRUGS SUITABLE FOR COLONIC DRUG DELIVERY. 

 B Pharmacy M pharmacy Study Material Pharmacology Notes DRUGS SUITABLE FOR COLONIC DRUG DELIVERY

DRUGS SUITABLE FOR COLONIC DRUG DELIVERY

Drug delivery selectively to the colon through the oral route is becoming increasingly popular for the treatment of large intestinal diseases and for systemic absorption of protein and peptide drugs. There has been an increasing interest in utilizing the colon as a site for systemic absorption of these drugs in view of the less hostile environment prevailing in the colon. A variety of protein and peptide drugs like calcitonin, interferon, interleukins, erythropoietin and even insulin are being investigated for their absorption using colon specific drug delivery (Mackay and Tomlinson., 1993).

Inflammatory bowel disease (IBD) such as ulcerative colitis and Crohn’s disease require selective local delivery of drugs to the colon. Sulfasalazine is the most commonly prescribed drug for such diseases. Selective delivery of the drug to the colon is required for therapeutic efficacy with less or no side effects. The other drugs used in IBD are steroids, such as dexamethasone, prednisolone, and hydrocortisone.  In colonic cancer, anticancer drugs like 5-flurouracil, doxorubicin, and nimustine are to be delivered specifically to the colon. The site specific delivery of drugs like, metronidazole, mebendazole, albendazole is used in the treatment of infectious diseases, such as amoebiasis and helmenthiasis (Krishnaiah et al., 2002b; Krishnaiah et al., 2001; Jain et al., 2004).

DRUGS SUITABLE FOR COLONIC DRUG DELIVERY pharmacology study material notesClick here to download

{DOC} B Pharmacy M pharmacy Study Material Pharmacology Notes DRUGS SUITABLE FOR COLONIC DRUG DELIVERY PDF B Pharmacy M pharmacy Study Material Pharmacology Notes DRUGS SUITABLE FOR COLONIC DRUG DELIVERY

Besides peptide and protein drugs, the colon is also a good site for the absorption of drugs that are not stable in the acidic environment of the stomach, cause gastric irritation (e.g. aspirin, iron supplements) or those degraded by small intestinal enzymes. A number of drugs available as sustained release or delayed release or timed release tablets or capsules for oral administration are anti-inflammatory drugs, anti-hypertensive drugs, etc. Unless these drugs have good absorption characteristics in the colon, their intended use in the management of respective disorders through sustained release or timed release formulations will be in question.  The drugs that are having good absorption properties from the colon include theophylline, glibenclamide (Brockmeier et al., 1985), and oxprenolol (Devis et al., 1988). Diclofenac, ibuprofen, nitrendipine, isosorbide, metoprolol, nifedipine etc. and hence can be investigated for better bioavailability through colon specific drug delivery (Fara, 1989).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[Doc PDF PPT ] Adenosine: Pharmacology notes B pharm M pharmacy Study Material

Adenosine Pharmacology notes for B M Pharmacy students

Pharmacology noted for B pharmacy and M Pharmacy students is readily available in our site www.pharmawiki.in/ [Doc PDF PPT ] Adenosine: Pharmacology notes B pharm M pharmacy Study Material is here below. Have a look at it and study it.

Adenosine is a purine nucleoside that regulates many physiological functions which includes respiratory regulation, neural function ,platelet aggregation, hormonal action , lymphocyte differentiation, vascular tone, negative chronotropic  and dromotropic effect on heart , also mediates inhibition of neurotransmitter release and lipolysis . These physiological function have been largely revised.(1),(2)

These functions are mediated through different adenosine receptor. There are four subtypes of AR-A1,A2A-AR,A2B-AR,A3-AR  each of these receptors has distinct tissue distribution and effector coupling. They belong to super family of G-protein coupled receptors (3).among these  receptors A1,A3AR1 are closely related  based on their sequence similarity while A2A,A2B AR also similarly related. A1 and A3 are primarly couple to G(subi) –family of G-protein.A2A and A2B are mostly coupled to GS  like G- protein. Each of these receptors plays an essential role in responding to adenosine in central nervous system(4) ,regulating pain (5) . cerebral blood flow(6). Basal gangalia function (7) respiration (8) and sleep (9.) thus these receptors can be therapeutic  targets for several diseases. Development of more selective agonists and antagonists  for adenosine receptor subtype provide aclass of therapeutics for treatment of numerous human diseases such as apain (10).  parkinsons disease (11)  asthma(12)   huntingtons disease(13).A search for new leads acting on specific adenosine acting on specific adenosine receptors may provide a key for novel therapeutics

Adenosine Pharmacology notes for B M Pharmacy students

Structure of A2A AR

        A2A-AR subtype is linked to  and G(S) and G(OLF) protein and up on activation the intracellular levels of Camp  are increased . the  expression  A2A AR expression is higest in brain, .spleen,thymus,leucocyte and blood platelets and intermediate in heart lungs and blood vessel.(14)(15)..Crystal structure of A2A AR was determined in 2008,physiological functions  A2A AR are regulation of sensori motors integration in basal ganglia., inhibition of platelet aggregation and polymorpho nuclear leucocytes, vasodilation protection  against ischemic damage, stimuation of sensory nerve activity . (17)  these wide range of functions implies their significant role in the body and use of chemical moieties to alter these function in disease state (may be agonists or antagonists).

A2A AR Adenosine antagonists:

A2A AR antagonist have their role in parkinsons disease, (18) keep regulations (19) controlling alcohol abuse (20) invivo receptor imaging (21)  there can also be used an anti depressant drug. (22) A2 AR agonists can be a treatment for ischemic renal injure (23) paraoxysmal supro ventricular tachycardia. They can be used as vasodilators (24) antithrombic agent (25)  antinflamatory (26) . they can also be used in treatment of asthma( 27), arthritis(28) sepsis (29) inflamatory bowel disease (30) and reduced skin pressure  ulcer formation (26) and accelerator  wound healing,(31)

In view of the role of A2A AR in these diseases afurther study in to the subject may reveal beneficial (facts) information for the treatment of such dieases. These receptors became agood targeting strategy  to bring out novel therapeutics for effective treatment of dieases.

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Pharmacology study material ADENOSINE Article REFRENCES:

(1) K. A. Jacoboson, Z.G.Gao, Adenosine receptors as therapeutic targets Nal.Rev., Drug Discovery 5(2006) 247-264

(2)M.P.Abbracchio, G.BUrnstock, A.verkhasatsky, H. Zimmermann, purinergic signalling in nervous system an over view ,Trends Neurosci. 32 (2009) 19-29

(3)B.B. Fredholm, G.Arsian, L.Halldner, B.kull, G.Schutte, W.Wasserman, structure and function of adenosine receptors and their genes , Naunyn – Schmiedebergs Arch.pnaarmacol.362 (2006) 19-29

(4)(a) . T.V Dunwiddie, S.A .Masina Annu . Rev.Neurosci 24,31(2001)

(b). K.A.Jacobson, Z.G.Gao , Nat .Rev Drug Discover.5,247 (2006)

(5) J.sawynok,x.J.Liv,Drog Neurobio . 69,313 (2003)
(6) Y.Shietal, J.Cereb Blood Flow Method . 28,111 (2008)

(7) M.A.Schwarzchild , L.Agnati, K. Fure, J. Fichsn, M.M orelli , Trends Neurobiol 29. 647 (2006)

(8) S.Lahiri, CH.Nitchell.D.Reigade , A.Roy , N.s.chemiack , Respir. Physiol. Nenrobiol. 157 ,123 (2007)

(9) R.Basheer,R.E.Strecker,MM.Thatkar,R.W.M.Carley Prog. Neurobiol.73,379 (2009)

(10)J,Sawynok,X.J.Liu. Prpg.Neurobio.69,313

(11)A.H.Schapira.et.al, Nat.Rev.Drug.Discor.5,845 (2006)
(12)A. Brow, D.Spina, C.p.page, Br.J.Pharmacol.153,(suppli),5446(2008)

(13)D.Blum, R.Hourez, M.C.Galar, P.Popoli,S.N.Schiftmann, Lancet Neurol.2,366(2003)

(14)F.Meng, G.X.Xic, D.Chalmeri, C.Margan,S.J.Watson,Jr.,H.Akil,Cloning and expression of the A2a  receptors from guinea pig brain Neuro chem 66(1996) 613-621

(15)R.A.Deter freud,M.Maccollin,J.Gusella,J.S.Flink Characterization and expression of the human A2a adenosine receptors gene, Neuro chem. 66(1996)362-368.

(16)Veli-Pekka Jaakola, Mark.T.Grifftin,Micheal, A.Hanson, Vadim cherezov , ellen y.t chien, J.Robert lane ,Adlioan, P.L.Jzerman, Raymond c.sterenes, the 2.6 Angstroun Crystal structure of a human A2a Adenosine  receptor Bound to an Antagonist

(17)B.B.Fredholm, Adenosine, an endogenous distress signal, modulates tissue damage and repair not cell death and differentiation (2007) 14, 1315-1323

(18)Michael A .Schwarzschild, Luigi Agnati, Kjell Fuxe ,Jiang – fanchen and micaela morelli, Targetting Adenosine A2a receptors in parkinsons disease Trends in neurosciences Vol.29 No.11

(19) Satoh, S., Matsumura, H. & Hayaishi, O. Involvement of adenosine A2A receptor in sleep promotion. Eur. J. Pharmacol. 351, 155–162 (1998

(20) Yao, L. et al. dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signalling and regulate ethanol consumption. Cell 109, 733–743 (2002).

(21) Moresco, R. M. et al. In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. Eur. J. Nucl. Med. Mol. Imaging 32,405–413 (2005).

(22) El Yacoubi, M. et al. Absence of the adenosine A2A receptor or its chronic blockade decrease ethanol withdrawal-induced seizures in mice. Neuropharmacology 40, 424–432 (2001).

(23) Okusa, M. D. et al. A2A adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion. Am.J. Physiol. Renal Physiol. 279, F809–F818 (2000).

(24) Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Klotz, K. N. & Linden, J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 53,527–552 (2001).

(25) Varani, K. et al. Dose and time effects of caffeine intake on human platelet adenosine A2A receptors:functional and biochemical aspects. Circulation 102,285–289 (2000)

(26) Peirce, S. M., Skalak, T. C., Rieger, J. M.,Macdonald, T. L. & Linden, J. Selective A2A adenosine receptor activation reduces skin pressure ulcer formation and inflammation. Am. J. Physiol. Heart Circ. Physiol. 281, H67–H74 (2001).

(27) Fozard, J. R., Ellis, K. M., Villela Dantas, M. F., Tigani, B. & Mazzoni, L. Effects of CGS 21680, a selective adenosine A2A receptor agonist, on allergic airways inflammation in the rat. Eur. J. Pharmacol438, 183–188 (2002).

(28) Montesinos, M. C. et al. Adenosine A2A or A3 receptors are required for inhibition of inflammation by methotrexate and its analog MX-68. Arthritis Rheum. 48, 240–247 (2003

(29) Sullivan, G. W., Fang, G., Linden, J. & Scheld, W. M. A2A adenosine receptor activation improves survival in mouse models of endotoxemia and sepsis. J. Infect. Dis. 189, 1897–1904 (2004).

(30) Odashima, M. et al. Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterology 129, 26–33 (2005).

(31) Montesinos, M. C. et al. Wound healing is accelerated by agonists of adenosine A2 (Gs-linked) receptors. J. Exp. Med. 186, 1615–1620 (1997).

{PDF PPT DOC} FILTRATION EQUIPMENT – Filtration Mechanism & Types – Adv + Disadvantages

{PDF PPT DOC} FILTRATION EQUIPMENT – Filtration Mechanism & Types – Adv + Disadvantages deals with details of filtration, filtration equipment,definitions, mechanism of filtration, Classification of filtration equipment, Different types of filtration its advantages & Disadvantages.

FILTRATION Definition:

FILTRATION may be defined as the separation of a solid from a fluid by means of a porous medium that retains the solid but allows the fluid to pass.

The term fluid includes liquids and gases, so that both these may be subjected to filtration.

The suspension of solid and liquid to be filtered is known as the “slurry”. The porous medium used to retain the solids is described as the filter medium; the accumulation of solids on the filter is referred to as the filter cake, while the clear liquid passing through the filter is the filtrate.

2.MECHANISMS OF FILTRATION:

The mechanisms whereby particles are retained by the filter are of significance only in the early stages of liquid filtration, as a rule. Once a preliminary layer of particles has been deposited, the filtration is effected by the filter cake, the filter medium serving only as a support.

STRAINING:

The simplest filtration procedure is “straining”, in which, like sieving, the pores are smaller than the particles, so that the latter are retained on the filter medium.

ENTANGLEMENT:

If the filter medium consists of a cloth with a nap or a porous felt, then particles become entangled in the mass of fibres. Usually the particles are smaller than the pores, so that it is possible that impingement is involved.

ATTRACTIVE FORCES:

In certain circumstances, particles may collect on a filter medium as a result of attractive forces. The ultimate in this method is the electrostatic precipitator, where large potential differences are used to remove the particles from air streams.

In practise, the process may combine the various mechanisms, but the solids removal is effected normally by a straining mechanism once the first complete layers of solids has begun to form the cake on the filter medium.

3.CLASSIFICATION OF THE FILTRATION EQUIPMENT:

Equipment’s are classified based on the application of external force.

  1. Pressure filters: plate and frame filter press and metafilter
  2. Vacuum filters: filter leaf
  3. Centrifugal filters

Classification based on the operation of the filtration

  1. Continuous filtration: discharge and filtrate are separated steadily and uninterrupted
  2. Discontinuous filtration: discharge of filtered solids is intermittent. Filtrate is removed continuously. The operation must be stopped to collect the solids.

Classification based on the nature of filtration

  1. Cake filters: remove large amounts of solids (sludge or crystals)
  2. Clarifying filters: remove small amounts of solids
  3. Cross-flow filters: feed of suspension flows under pressure at a fairly high velocity across the filter medium.

Equipment’s of pharmaceutical interest:

  1. Sand filters:
  2. Filter presses: chamber, plate and frame filters ( non-washing/washing; closed delivery/open delivery)
  3. Leaf filters
  4. Edge filters: stream line and meta filters
  5. Rotary continuous filters
  6. Membrane filters
  1. FILTRATION EQUIPMENT:

  2. {PDF PPT DOC} FILTRATION EQUIPMENT - Filtration Mechanism & Types - Adv + Disadvantages

4.1.SAND FILTERS

 

These are used mainly when relatively small amounts of solid are to be removed from the liquid and when relatively large volumes of liquid must be handled at minimum cost. A standardised pressure sand filter consists of a cylindrical tank at the bottom of which are a number of brass strainers which are either mounted on a false bottom or connected to a manifold embedded in concrete. The strainers have narrow slots sawed in them. Over the strainers is a layer of several inches of moderately coarse gravel on the top of which is a 2 to 4 ft. deep sand layer that forms the actual filter medium. The water to be filtered is introduced at the top on to a baffle which prevents disturbance in the sand by a direct stream. The filtered water is drawn off through the strainers at the bottom. When the precipitate clogs the sand to the extent of retarding the flow of water, it is removed by back washing. This operation consists of introducing water through the strainers, so that it may flow up through the sand bed and-out through the connection that is normally the inlet. This wash water is wasted. These sand filters are applicable only to the separation of precipitates that can be removed from the sand in this manner and that are to be discarded. Gelatinous precipitates or precipitates that coat the sand so that they cannot be removed by back washing or precipitates that are to be recovered cannot be handled in the sand filter.

Capacity is usually 2 to 4 gpm/sq.ft of surface of filtering area.

Fig1: pressure sand filter

For filtering excessively large quantities of very clean water, an open or rapid sand filter is used. It is similar to the pressure sand filter except that the sand is contained in large, open concrete boxes instead of in a closed pressure tank. Sand filter used in this way becomes a gravity filter (also called hydrostatic head filter).

ADVANTAGES:

Gravity filters have advantages of extreme simplicity, needing only simple accessories, low first cost and can be made of almost any material.

DISADVANTAGES:

  • Relatively low rate of filtration.
  • Excessive floor area needed and high labour charges
  • If the amount of particulate matter to be removed is too small or it is finely divided, sand filter will not remove the suspended solids.
  • In processes involving organic materials there may be danger of bacterial infection from an infected process-water supply and the sand filter cannot remove the bacteria as such. In these cases a coagulant like ferrous sulphate or aluminium sulphate is added to the water before filtration. These are hydrolysed by the alkalinity of most normal waters with the formation of a flocculant precipitate of iron or aluminium hydroxide. This precipitate adsorbs finely divided suspended matter and even bacteria, even if added to the water in very small amounts. The resultant flocs, though fine, are removed by the sand filters.

4.2.PLATE AND FRAME FILTER PRESS:

.

Principle : The mechanism is surface filtration. The slurry enters the frame by pressure and flows through the filter medium: The filtrate is collected on the plates and sent to the outlet. A number of frames and plates are used so that surface area increases and consequently large volumes of slurry can be processed simultaneously with or without washing.

Construction .: The construction of a plate and frame filter press is shown in the figure2. The filter press is made of two types of units, plates and frames.

(a) Frame-Maintains the slurry reservoir, inlet (eye) for slurry.

(b) Filter medium.

(c) Plate along with section-supports the filter medium, receiving the filtrate and outlet (eye).. (d) Assemb1y of plate and frame filter press.

These are usually made of aluminium alloy. Sometimes these are also lacquered for protection against corrosive chemicals and made suitable for steam sterilisation.

Frame contains an open space inside wherein the slurry reservoir is maintained for filtration and an inlet to receive the slurry. It is indicated by two dots in the description (Figure ).The plate has a studded or grooved surface to support the filter cloth and an outlet. It is indicated by one dot in the description (Figure ). The filter medium (usually cloth) is interposed between plate and frame.

Frames of different thicknesses are available. It is selected based on the thickness of the cake formed during filtration. Optimum thickness of the frame should be chosen. Plate, filter medium, frame, filter medium and plate are arranged in the sequence and clamped to a supporting structure. It is normally described by dots as 1.2.1.2.1 so on. A number of plates and frames are employed so that filtration area is a large as necessary. In other words, a number of filtration units are operated in parallel. Channels for the slurry inlet and filtrate outlet can be arranged by fitting eyes to the plates and frames, these join together to form a channel. In some types, only one inlet channel is formed, while each plate is having individual outlets controlled by valves.

Working : The working of the frame and plate process can be described in two steps, namely filtration and washing of  the cake (if desirable).

 

Filtration operation : The working of a plate and frame press is shown in Figure. Slurry enters the frame (marked by 2 dots) from the feed channel and passes through the filter medium on to the surface of the plate (marked by I dot). The solids form a filter cake and remain in the frame. The thickness of the cake is half of the frame thickness, because on each side of the frame filtration occur. Thus, two filter cakes are formed, which meet eventually in the centre of the frame. In general, there will be an optimum thickness of filter cake for any slurry, depending on the solid content in the slurry and the resistance -of the

filter cake.

The filtrate drains between the projections on the surface of the plate and escapes from the outlet. As filtration proceeds, the resistance of the cake increase and the filtration rate decreases. At a certain point, is preferable to stop the process rather than continuing at very low flow rates. The press is emptied and the cycle is restarted.

Fig 3: plate and frame filter press

Washing operation: If it is necessary to wash the filter cake, the ordinary plate and frame press is unsatisfactory. Two cakes are built up in the frame meeting eventually in the middle. This means that flow is brought virtually to a stand still. Hence, water wash using the same channels of the filtrate is very inefficient, if not  impossible. A modification of the plate and frame press is used. For this purpose, an additional channel is included (Figure). These wash plates are identified by three dots. In half the wash  plate there is a connection from the wash water channel to the surface of the plate.

The sequence of arrangement of plates and frames can be represented by dQts as 1.2.3.2.1.2.3.2.1.2.3.2.1 so on (between I and 1,2.3.2 must be arranged). Such an arrangement is shown in Figure (a) and (b) for the operations of filtration and water washing, respectively.

The steps are as follows.

(1) Filtration proceeds in the ordinary way until the frames are filled with cake.

(2) To wash the filter cake, the outlets of the washing plates (three dots) are closed.

(3) Wash water is pumped into the washing channel. The water enters through the inlets on to the surface     of the washing (three dots) plates.

(4) Water passes through the filter cloth and enters frame (two dots) which contains the cake. Then water washes the cake, passes through the filter cloth and enters the plate (one dot) down the surface.

(5)Finally washed water escapes through the outlet of that plate.

Fig 4: plate and frame filter press with water wash facility

Thus with the help of special washing plates, it is possible for the wash-water to flow over the entire surface of washing (three dots) plate, so that the flow resistance of the cake is equal to all points. Hence, the entire cake is washed with equal efficiency.

Fig 5: principles of filtration and washing

It should be noted that water- wash is efficient only if the frames are full with filter cake. If the solids do not fill the frame completely, the wash water causes the cake to break (on the washing plate side of the frame) then washing will be less effective. Hence, it is essential to allow the frames become completely filled with the cake. This helps not only in emptying the frames but also helps in washing the cake correctly.

Special provisions:

(I) Any possible contamination can be observed by passing the filtrate through a glass tube or sight glass from the outlet on each plate. This permits the inspection of quality of the filtrate. The filtrate goes through the control valve to an outlet channel.

(2) The filtration process from each plate can be seen. In the event of a broken cloth, the faulty plate can be isolated and filtration can be continued with one plate less.

Uses : Filter sheets composed of asbestos and cellulose are capable of retaining bacteria, so that sterile filtrate can be obtained, provided that the whole filter press and filter medium have been previously sterilized. Usually steam is passed through the assembled unit for sterilization.

Examples include collection of precipitated antitoxin, removal of precipitated proteins from insulin liquors and removal of cell broth from the fermentation medium.

Heating/cooling coils are incorporated in the press so as to make it suitable for the filtration of viscous liquids .

Advantages :

(1) Construction of filter press is very simple and a variety of materials can be used.

– Cast iron for handling common substances.

— Bronze for smaller units.

– Stainless steel is used there by contamination can be avoided.

– Hard rubber or plastics where metal must be avoided.

– Wood for lightness though it must be kept wet.

(2) It provides a large filtering area in a relatively small floor space. It is versatile, the capacity being variable according to the thickness of frames and the number used. Surface area can be increased by employing chambers up to 60.

(3) The sturdy construction permits the use of considerable pressure difference. About 2000 kilopascals can’ be normally used.

(4) Efficient washing of the cake is possible.

(5) Operation and maintenance is straight forward, because there are no moving parts, filter cloths are easily renewable. Since all joints are external, a plate can be disconnected if any leaks are visible. Thus contamination of the filtrate can be avoided.

(6) It produces dry cake in the form of slab.

Disadvantages :

(I)it is a batch filters so there is a good deal of ‘down-time’, which is non-productive.

(2) The filter press is an expensive filter. The emptying time, the labour involved and the wear and tear of the cloth resulting in high costs.

(3)operation is critical, as the frames should be full, otherwise washing is inefficient and the cake is difficult to remove.

(4) The filter press is used for slurries containing less than 5% solids.  So high costs make it  imperative that this filter press is used for expensive materials. Examples include the collection of precipitated antitoxin and removal of precipitated proteins from insulin liquors.

4.3.FILTER LEAF:

The filter leaf is probably the simplest  form, of  filter, consisting of a frame enclosing a drainage screen or grooved  plate, the whole unit being covered with filter cloth. The outlet for the filtrate connects to the inside of the frame. The frame may be of any shape, circular, square or rectangular shapes being used in practice. In use, the filter leaf is

immersed in the slurry’ and a receiver and vacuum system connected to the filtrate outlet. The method has the advantage that the slurry can be filtered from any vessel and the cake can be washed simply by immersing the filter, in a vessel of water. Removal of the cake is facilitated by the use of reverse air flow.

An alternative method is to enclose the filter leaf in a special vessel into which the slurry is pumped under pressure.

This form is commonest in filters where a number of leaves are connected to common outlet, to provide a larger area for filtration. A typical example is “ the Sweetland filters

Fig 6: filter leaf                                              Fig 7: sweetland filter

The filter leaf is a versatile piece of equipment. Area can be varied by employing a suitable number of units, and the pressure difference may be obtained with vacuum or by using pressures up to order of 8 bars. The leaf filter is most satisfactory if the solids content of slurry is not too high, about 5 per cent being a suitable maximum. A higher proportion, results in excessive non-productive time while the filter being emptied and, provided this is observed. Labour costs for operating the filter are comparatively moderate·

The special feature of the leaf filter is the high efficiency of washing; in fact the cake can be dislodged and refiltred from the wash water if desired.

 

4.4.ROTARY FILTER:

Filters such as the filter leaf and filter press are batch operated and can handle dilute suspensions only, if the process is to be economic. In large scale operation, continuous operation is sometimes desirable and it may be necessary to filter slurries containing a high proportion of solids.

The rotary filter is continuous in operation and has a system for removing the cake that is formed, hence it is suitable for use with concentrated slurries.

The rotary filter consists of a number of filter units (usually 16-20 )  arranged so that the units are passing in continuous succession through the various stages.

One form is the rotary disc filter in which the sectors shaped filter leafs form a disc with the outlet from the each leaf connected to the vacuum system, compressed air, and the appropriate receivers, in the correct sequence, by means of special rotating valve.

fig 8: Rotary drum filter

The commonest form in use in the pharmaceutical industry, however, is the rotary drum filters, a section of which is shown in figure, from which it will be seen that the filter units have the shape of longitudinal segments of the pheriphery of a cylinder. Thus, each filter unit is rectangular in shape with a curved profile so that a number can be joined up to form a drum. Each unit has a perforated metal surface to the outer part of the drum and is covered with filter cloth. Appropriate connections are again made from each unit through a rotating valve at the center of the drum. In operation, the drum rotates at low speed, so that cach unit passes through the various zones shown in figure and listed in table.

Rotary filters may be up to 2m in diameter and 3.5m in length, giving areas of the order of 20m2. Special attachments may be included for special purposes; for example if the cake shrinks and cracks as it dries out, cake compression rollers can be fitted. These compress the cake to a homogenous mass to improve the efficiency of washing as the cake passes through the washing zone, or to aid drainage of wash water as the cake passes to the drying zone.

Where the solids of the slurry are such that the filter cloth becomes blocked with the particles, a pre coat filter may be used. This is variant in which a precoat of filter aid is deposited on the drum prior to the filtration process. The scraper knife then removes the solid filtered from the slurry together with a small amount amount of the precoat, the knife advancing slowly as the precoat is removed.

If the removal of the cake presents the problems, alternative discharge methods can be used. The string discharge rotary filter, for example, is especially useful for certain pharmaceutical applications, particularly for filtering the fermentation liquor in the manufacture of antibiotics where the mould is difficult to filter by ordinary methods because it forms a felt-like cake. The string discharge filter is operated by means of a number of loops of string which pass the drum, and cause the cake to form over the strings as shown in the diagram. The strings are in contact with the surface of the drum up to the cake removal zone, where they leave the surface and pass over additional small rollers before returning to again contact the drum. In operation, the strings lift the filter cake of the filter medium, and the cake is broken by the sharp bend, over the rollers so that it is easily collected while the strings return to the drum.

Advantages:

 

(a) The rotary filter is automatic and is continuous in operation, so that labour costs are very low

(b) the filter has a large capacity, in fact, the area of the filter as represented by A of darcy’s law is infinity.

(c) variation of the speed of rotation enables the cake thickness to be controlled and for solids that form an impermeable cake, the thickness may be limited to less than 5mm. On the other hand, if the solids are coarse, forming a porous cake, the thickness may be 100mm or more.

Table 1: various zones in rotary filter.

Fig 9: string discharge rotary drum filter

Disadvantages:

  • The rotary filter is a complex piece of equipment with many moving parts and is very expensive and in addition to the filter itself, ancillary equipments such as vacuum pumps and vacuum receivers and traps, slurry pumps and agitators are required.
  • The cake tends to crack due to the air drawn through by the vacuum system so that washing and drying are not efficient.
  • Being a vaccum filter the pressure difference is limited to 1 bar and hot filtrates may boil.
  • The rotary filter is suitable only for straight forward slurries,being less satisfactory if the solids formed an impermeable cake or will not separate cleanly from the cloth.

USES OF THE ROTARY FILTERS:

The rotary filter is most suitable for continuous operation on large quantities of slurry, especially if the slurry contains considerable amounts of solids, i.e., in the range 15-30%.

Examples of pharmaceutical applications include the collection of calcium carbonate, magnesium carbonate and starch, and the separation of mycelium from tyhe fermentation liquor in the manufacture of antibiotics.

4.5.MEMBRANE FILTERS:

These are plastic membranes based on cellulose acetate, cellulose nitrate or mixed cellulose esters with pore sizes in the micron or submicron range. They are very thin (about 120 micron thick) and must be handled carefully. They act like a sieve trapping particulate matter on their surface.

Several grades of filters are available with pore sizes ranging from 0.010 ± 0.002

micron to 5.0 ± 1.2 micron. Type codes VF and SM are given by Millipore Filter Corp. for

these two extreme ranges respectively.

Filters with pore sizes from 0.010 to 0.10 micron can remove virus particles from water or air. Filters with pore sizes from 0.30 to 0.65 microns are employed for removing bacteria. Filters with the larger pore sizes, viz. 0.8, 1.2 and 3.0 to 5.0 microns are employed, for example, in aerosol, radio activity and particle sizing applications.

During use membrane filters are supported on a rigid base of perforated metal, plastic or coarse sintered glass as in the case of fibrous pad filters. If the solution to be filtered contains a considerable quantity of suspended matter, preliminary filtration through a suitable depth filter avoids clogging of the membrane filter during sterile filtration. They are brittle when dry and can be stored indefinitely in the dry state but are fairly tough when wet.

ADVANTAGES:

  • No bacterial growth through the filter takes place during prolonged filtration.
  • They are disposable and hence no cross contamination takes place.
  • Adsorption is negligible they yield no fibres or alkali into the filterate. Filtration rate is rapid.

 

DISADVANTAGES:

  • They may clog though rarely.
  • Ordinary types are less resistant to solvents like chloroform

 

4.6.EDGE FILTERS:

A form of filters that differs markedly from those described above is the type known generally as edge filters. Filters such as the leaf or press act by presenting a surface of the filter medium to the slurry. Edge filters use a pack of the filter medium, so that filtration occurs on the edges. Forms using packs of media such as filter paper can be used but in the pharmaceutical industry greatest use is made of the Metafilter.

4.7.METAFILTER:

The metafilter, in its simplest form, consists of a grooved drainage rod on which is packed a series of metal rings. These rings, usually of stainless steel, are about 15mm inside diameter, and 0.8mm in thickness, with a number of semi-circular projections on one surface, as shown in the figure. The height of the projections and the shape of the section of the ring are such as that when the rings are packed together, all the same way up, and tightened on the drainage rod with a nut, channels are formed that taper from about 250µm down to 25µm. One or more of these packs is mounted in a vessel, and the filter may be operated by pumping in the slurry under pressure or, occasionally, by the application of reduced pressure to the outlet side.

In this form, the metafilter can be used as a strainer for coarse particles, but for finer  particles a bed of a suitable material such kieselguhr is first built up. The pack of rings, therefore, serves essentially as a base on which the true filter medium is supported.

Advantages

 

(a) The metafilter possesses considerable strength and high pressures can be used, with no danger of bursting the filter medium.

(b)As there is no filter medium as such, the running costs are low, and it is a very economical

filter.

(c) The metafilter can be made from materials that can provide excellent resistance to corrosion and avoid contamination of the most sensitive product.

(d) by selection of a suitable grade of material to form the bed, it is possible to filter off very fine particles; in fact, it is claimed that some grade will sterilize some liquid by filteration. Equally well it is possible to remove larger particles simply by building up a bed of coarse substances, or even by using the meta filter candle itself if the particles are sufficiently large.

(e) Removal of the cake is effectively carried out by back flushing with water. If further cleaning is required, it is normally necessary to do more than slacken the clamping nut on the end of the drainage rod on which the rings are packed.

Fig:10 (a) surface view ring ,

                                             (b) section through filter

USES OF THE METAFILTER:

 

The small surface of the metafilter restricts the amount of the solids that can be collected. This, together with the ability to separate very fine particles, means that the metafilter is used almost exclusively for clarification purposes.

Furthermore, the strength of the metafilter permits the use of high pressures (15 bars) making the method suitable for viscous liquids. Also, it can be constructed with material appropriate for corrosive materials. Specific examples of pharmaceutical uses include the clarification os syrups, of injection solutions, and of products such as insulin liquors.

CONCLUSION:

Filtration is an unique unit operation. The seperative process of filtration is widely used in the biopharmaceutical industry to remove contaminants from liquids, air, and gases, such as particulate matter, micro organisms. So a thorough knowledge of filtration equipment and their integrity testing is essential.

References:

  1. Cooper and Gunn’s. Tutorial Pharmacy by S.J.Carter.
  2. Pharmaceutical engineering; K. Sambamurthy
  3. Pharmaceutical engineering; principles and practices, C.V.S. Subrahmanyam
  4. Encyclopedia of pharmaceutical technology, vol 3, edited by James Swarbrick.
  5. Pikal, M.J.; Lukes, A.L.; Lang, J.E. Thermal decomposition of amorphous beta-lactam antibacterials. J. Pharm. Sci. 1977, 66, 1312–1316.
  6. Pikal, M.J.; Lukes, A.L.; Lang, J.E.; Gaines, K. Quantitative crystallinity determinations of beta-lactam antibiotics by solution calorimetry: correlations with stability. J. Pharm. Sci. 1978, 67, 767–773.
  7. Pikal, M.J.; Dellerman, K.M. Stability testing of pharmaceuticals by high-sensitivity isothermal calorimetry at 25_C: cephalosporins in the solid and aqueous solution states. Int. J. Pharm. 1989, 50, 233–252
  8. batch and continuous filtration,pharmaceutical filtration ppt, factors affecting rate of filtration, filtration ppt presentation, theory of filtration ppt, advantages and disadvantages of filtration of water,
    rate of filtration calculation, filtration techniques ppt, types filtration equipment, filtration equipment pdf,
    filtration equipment ppt, simple filtration equipment, filtration equipment chemistry, types of filtration process, types of water filtration, types of filtration pdf.

Filtration equipment pdf

filtration equipment pdf,PDF PPT DOC Pharmaceutical FILTRATION EQUIPMENT – Filtration Mechanism & Types – Adv Disadvantages

What is Intellectual Property? Intellectual Property Rights & Regulatory Affairs-2

What is Intellectual Property?

The inventor of a machine, the author of a book, or the writer of music somehow usually ‘own’ their work. From this ownership, certain consequences flow and you probably have been made aware of the fact that we cannot just copy or buy a copy of their works without consideration of their rights. Equally, original industrial designs of furniture, wallpaper and the like seem naturally to be owned by someone or some organization.
Each time we buy such ‘protected’ items, a part of what we pay goes back to the owner as recompense for the time, money, effort and thought they put into the creation of the work. This has resulted over the years in the  development of industries such as the music industry growing worldwide and encouraging new talent to produce more and more original ideas and articles.

What is Intellectual Property? Intellectual Property Rights & Regulatory Affairs-2

The following suggests some of the things that are entitled to protection as intellectual property under national intellectual property laws and / or various international treaties:

Discs

  • Performances
  • Videos
  • Computer games
  • Broadcasts
  • Computer programs

Designs for objects

  • Images
  • Logos
  • Trademarks
  • Integrated circuits
  • Inventions

Geographical indications of origin for certain types of products

  • Chemical formulas
  • Companies’ names
  • Perfumes
  • Industrial processes
  • Materials

The outstanding features that most types of property share are that the owner of the property is free to use it as she/he wishes, provided the use is not against the law, and to exclude others from so using that owned item of property. Now the term “intellectual property” is reserved for types of property that result from creations of the human mind, the intellect. Interestingly, the term intellectual property in the Convention Establishing the World Intellectual Property Organization, or “WIPO”, does not have a more formal definition. 
The States that drafted the Convention chose to offer an inclusive list of the rights as relating to:
“Literary artistic and scientific works; performances of performing artists, phonograms, and broadcasts; inventions in
all fields of human endeavor; scientific discoveries; industrial designs; trademarks, service marks, and commercial names and designations; protection against unfair competition; and “all other rights resulting from intellectual activity in the industrial, scientific, literary or artistic fields.”

Intellectual property is usually deals with the following:

1) Literary, artistic and scientific works
e.g. books.
Protection of this property is governed by laws concerning Copyright.
2) Performances, broadcasts e.g. concerts.
Protection of this property is governed by laws concerning Copyright’s Related Rights.
3) Inventions
e.g. a new form of jet engine. Protection of inventions is covered by laws concerning Patents.
4) Industrial designs
e.g. the shape of a soft drinks bottle.
Industrial Designs may be protected by its own specialized laws, or those of Industrial Property or Copyright.
5) Trademarks, service marks and commercial names and designations e.g. logos or names for a product with unique geographical origin, such as Champagne.
Protection is normally available under various laws. In this course the laws are covered within the Trademark module.
6) Protection against unfair competition.
e.g. false claims against a competitor or imitating a competitor with a view
to deceive the customer. This is a theme that occurs in many of the modules in this course and is in fact the subject of a separate module.

Principles:

Common to all of the areas are two principles:
• The creators of intellectual property can acquire rights as a result of their work.
• The rights to that work may be assigned or licensed to others.

Importance of Intellectual Property Rights:

Intellectual Property Rights really matter. Do you know why?The first reason is that it is both just and appropriate that the person putting in the work and effort into an intellectual creation has some benefit as a result of this endeavor. The second reason is that by giving protection to intellectual property many such endeavors are encouraged and industries based on such work can grow, as people see that such work brings financial return. Intellectual property rights may also help to extend protection to such things as the unwritten and unrecorded cultural expression of many developing countries, generally known as folklore. With such protection they may be exploited to the benefit of the country and cultures of origin.

The reason for States to enact national legislation, and to join as signatories to either (or both) regional or international treaties governing intellectual property rights include:
• to provide incentive towards various creative endeavors of the mind by offering protections;
• to give such creators official recognition;
• to create repositories of vital information;
• to facilitate the growth of both domestic industry or culture, and international trade, through the treaties offering multi-lateral protection.

Source: World Intellectual Property Organization, or “WIPO“4

Intellectual Property Rights {IPR} & Regulatory Affairs 1 SUPAC

Intellectual Property Rights {IPR} & Regulatory Affairs 1 SUPAC

SCALE UP & POST APPROVAL CHANGES (SUPAC)

The scale-up process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as Scale-Up and post approval Changes, or SUPAC.

Intellectual Property Rights {IPR} & Regulatory Affairs

In the process of developing a new drug product, the batch sizes used in the earliest  human studies are small. As one proceeds through Phase 1 testing (i.e., the first introduction of a new chemical entity to humans), Phase 2 (discovering an indication for use), and Phase 3 (determining dose, side-effect profile, etc.), the size of the batches is grSadually increased. When a New Drug Application (NDA) is approved by the Food and Drug Administration (FDA), the drug product is scaled up to a significantly larger batch size to meet the demands of the anticipated market.

Intellectual Property Rights {IPR} & Regulatory Affairs 1 SUPAC

Similarly, in the development of a generic version of an already approved marketed product, a small batch is produced and tested for, among other things, bioequivalence to the FDA reference listed drug product. When the generic product meets FDA approval criteria, the Abbreviated New Drug Application (ANDA) or generic antibiotic application (AADA) is approved for marketing. It, too, is then scaled up to meet the demands of its anticipated market. Whether a new chemical entity being brought to market for the first time or an approved generic version of previously marketed product, the size of the batch is almost inevitably scaled up to a significantly larger batch. In the process of scaling up, certain changes in the formula (composition) and/or in the manufacturing process and/or in the equipment may be necessary. In addition, the site at which the product will be manufactured may differ from where the smaller (pilot) batches were manufactured. The scale-up process and the changes made after approval in the composition, manufacturing process, manufacturing equipment, and change of site have become known as Scale-Up and post approval Changes, or SUPAC. The FDA has issued various guidance for SUPAC changes designated SUPAC-IR1 (for immediate-release solid oral dosage forms), SUPAC-MR2 (for modified-release solid oral dosage forms), and SUPAC-SS3 (for non-sterile semisolid dosage forms including creams, ointments, gels, and lotions).

SUPAC – Pharmacy Assignments Projects PPT’s

Although scale-up may occur at any point in the lifetime of a product, it most often occurs after the firm has been notified that the drug product is approvable, i.e., it meets all the conditions required by the FDA for marketing. With the submittal of Final Printed Labeling, a showing that the marketed product will meet the conditions for marketing as approved by the FDA (and in the case of generics, production of three consecutive scaled-up batches), and satisfactory completion of a pre-approval inspection by the local FDA district office, the product is formally approved to be manufactured and sold in the United States. At this point, SUPAC begins to exert its effect.

Pharma Assignments Projects PPT’s Power Point Presentation PDF:

Although SUPAC is a means of decreasing regulatory burden by empowering industry to make regulatory decisions, it does not affect any compliance or inspection requirement. It also is limited to scale-up and post-approval changes, even though the underlying science applies to pre-approval changes as well. The major affect of SUPAC is a significant decrease in the time required to implement changes.

Download Intellectual Property Rights IPR & Regulatory Affairs Material SUPAC 1

 

SUPAC:

The premise of the consensus White Papers was that if:
1) The source of the drug substance for the smaller and larger batches was the same;
2) The drug substance particle size (both mean and distribution) was the same;
3) The excipients were the same;
4) The excipient particle size (both mean and distribution) was the same;
5) The order of addition was the same;
6) The equipment was the same;
7) The processing was the same; and, most important,
8) A surrogate test for bioequivalence testing (dissolution) was the same, the two batches were indeed the same. Over the previous 20 years the FDA, Bio-pharmaceutics Program had established that with indefinable limits, dissolution was predictive of in vivo bioequivalence, for the same formulation, processed under the same conditions, on the same equipment. These criteria became the fundamental principle of the SUPAC initiative. (The percutaneous diffusion testis similarly used as a surrogate bioequivalence test for non-sterile, semisolid formulations.)To establish the validity of the approach recommended by the three consensus papers, the FDAcontracted the College of Pharmacy of the University of Maryland to study several drug products chosen on the basis of their solubility and permeability. The data revealed that the workshop recommendations were conservative and could be safely implemented. In fact, the studies showed that even broad differences in in vitro dissolution that resulted from major compositional changes failed to translate into bioavailability differences. Subsequently, the FDA published its SUPAC Guidance for Immediate Release Solid Oral Dosage Forms and followed with guidances for modified-release (controlled-release) and non-sterile semisolid dosage forms. In November 1999 (modified slightly in December 1999), the FDA extended the SUPAC
concept to address changes in analytical methodology, packaging, and Labeling and sterile semi solid dosage forms. This last guidance also updated the previously published guidances on immediate-release, modified-release, and non-sterile,
semisolid dosage forms. In particular, the issue of multiple post approval changes(which had been addressed differently in the previously published guidances) were now the same. The FDA now allowed multiple post approval changes for every solid oral dosage form, using the same requirements a sits SUPAC Semisolid Guidance. The SUPAC Guidances published by the FDA define various levels of change and for each level of change specifies the
1) Recommended chemistry, manufacturing, and control tests;
2) In vitro dissolution testing and/or in vivo bioequivalence tests; and 3) Documentation that the FDA requires to be filed in the NDA, ANDA, or AADA to support the change. These guidances do not affect other compliance or inspection documentation required by the FDA Centre for Drug Evaluation and Research Office of Compliance (CDER-OC) or the FDA field investigation units.

 

 

 

[PPT] Multiple Emulsions “Formulation Stability & Drug Delivery”


Contents of the powerpoint on Multiple Emulsions include:
INTRODUCTION
FORMULATION OF MULTIPLE EMULSIONS
PREPARATION OF MULTIPLE EMULSIONS
CHARACTERISATIONOFMULTIPLEEMULSIONS
STABILITY OF MULTIPLE EMULSIONS
STABILITY ASSESSMENT STUDIES
DRUG RELEASE FROM MULTIPLE EMULSIONS
BIOAVAILABILITY
APPLICATIONS
CONCLUSION
REFERENCES

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Let’s delve into each aspect of multiple emulsions in detail.

Introduction to Multiple Emulsions

Multiple emulsions, also known as “W/O/W” or water-in-oil-in-water emulsions, are complex systems that involve the dispersion of both oil and water phases within one another. These emulsions are characterized by a double-layered structure, where an inner water phase is surrounded by an oil phase, which is, in turn, encapsulated by another outer water phase. Multiple emulsions have garnered significant interest in various industries due to their unique properties, including the ability to encapsulate and deliver both hydrophilic (water-soluble) and lipophilic (oil-soluble) compounds simultaneously. This makes them particularly valuable in pharmaceuticals, cosmetics, and food products, where controlled release and improved stability are critical.

Formulation of Multiple Emulsions

The formulation of multiple emulsions involves careful consideration of the specific objectives and the desired properties of the emulsion. The main components in multiple emulsion formulation include:

Primary Emulsion (W/O): This innermost phase typically consists of water-soluble compounds or hydrophilic drugs. It forms the core of the multiple emulsion.

W/O Interface: An intermediate layer contains emulsifying agents, stabilizers, or polymers, which help prevent phase separation between the inner and outer phases. The interface plays a crucial role in maintaining the integrity of the multiple emulsion structure.

Secondary Emulsion (O/W): The outer phase is usually composed of oil, which may contain lipophilic compounds or drugs. This phase surrounds the primary emulsion, forming the final double-layered structure.

Preparation of Multiple Emulsions

Multiple emulsions can be prepared using various techniques, depending on the desired structure and characteristics. Two common methods include:

Two-Step Emulsification: This approach involves creating the primary emulsion first, which is typically a water-in-oil (W/O) emulsion. Then, the outer aqueous phase is added to form the final water-in-oil-in-water (W/O/W) multiple emulsion. This method allows for precise control over the composition of both the inner and outer phases.

Phase Inversion Method: The phase inversion method exploits changes in temperature or the addition of co-surfactants to induce a phase inversion between the primary emulsion (W/O) and the secondary emulsion (O/W). This technique can lead to the formation of multiple emulsions with different properties.

Characterization of Multiple Emulsions

Understanding and controlling the properties of multiple emulsions is crucial for optimizing their performance. Various characterization techniques are used to assess their structure, stability, and physical properties:

Microscopy: Optical and electron microscopy are employed to visualize the internal structure of multiple emulsions. This helps in observing the distribution of droplets within the emulsion.

Particle Size Analysis: Determining the size distribution of droplets in the emulsion is essential for assessing stability and predicting behavior. Techniques like dynamic light scattering (DLS) or laser diffraction are commonly used for this purpose.

Rheology: Rheological measurements help in understanding the viscosity and flow behavior of multiple emulsions. This information is critical for applications such as cosmetics and food products.

Zeta Potential: Zeta potential measurements provide insights into the surface charge of droplets. This parameter affects stability, as droplets with higher or lower surface charges may repel or attract each other, influencing aggregation and coalescence.

Stability of Multiple Emulsions

Ensuring the long-term stability of multiple emulsions is a significant challenge. Several factors can impact stability, and they need to be carefully addressed:

Ostwald Ripening: This phenomenon involves the continuous growth of larger droplets at the expense of smaller ones. It can lead to instability by causing changes in the size distribution of droplets.

Flocculation and Creaming: Flocculation refers to the aggregation or clustering of droplets. Creaming occurs when droplets migrate to the top or bottom of the emulsion due to density differences. Both can lead to phase separation.

Coalescence: Coalescence involves the merging of neighboring droplets, which can result in the formation of larger droplets and eventual phase separation.

Stability Assessment Studies

To address the challenges of stability in multiple emulsions, various stability assessment studies are conducted:

Accelerated Stability Testing: Multiple emulsions are subjected to extreme conditions, such as high temperatures or freeze-thaw cycles, to predict their long-term stability under harsh environmental conditions.

Freeze-Thaw Cycling: This test simulates temperature fluctuations that may occur during storage or transportation, helping to evaluate the emulsion’s resilience to thermal stress.

Centrifugation: Centrifugation is used to assess phase separation under force. It helps determine the emulsion’s stability when subjected to mechanical stress.

Visual Inspection: Regular visual inspection is essential for monitoring changes in the emulsion’s appearance, including color, clarity, and phase separation. Any signs of instability need to be addressed promptly.

Drug Release from Multiple Emulsions

Multiple emulsions find significant applications in controlled drug release. Several factors influence drug release from these emulsions:

Emulsion Composition: The choice of whether the drug is placed in the inner (W/O) or outer (O/W) phase impacts its release. Hydrophilic drugs are often placed in the inner phase, while lipophilic drugs are incorporated into the outer phase.

Emulsifier Type: The type and concentration of emulsifiers can significantly affect drug solubility within the emulsion. Proper selection is essential for achieving the desired release profile.

Drug Loading: The concentration of the drug in the emulsion can be adjusted to control the release rate. Higher drug concentrations typically result in faster release.

External Phase Viscosity: Altering the viscosity of the outer (O/W) phase can influence drug release kinetics. Higher viscosity can slow down drug diffusion.

Bioavailability

In pharmaceutical applications, the bioavailability of drugs delivered via multiple emulsions is of utmost importance. Several factors can impact bioavailability:

Droplet Size: Smaller droplets provide a larger surface area for drug absorption, potentially enhancing bioavailability.

Emulsifier Choice: The type and concentration of emulsifiers can affect drug solubility and stability within the emulsion. Proper selection is crucial for optimizing bioavailability.

Formulation: Adjusting the ratio of the oil to water phases can influence drug release and absorption. Finding the right balance is critical.

Patient Factors: Individual variations in physiology, metabolism, and gastrointestinal (GI) tract conditions can influence drug absorption and, consequently, bioavailability.

In conclusion, multiple emulsions are versatile systems with wide-ranging applications. Understanding their formulation, preparation, characterization, stability assessment, drug release mechanisms, and bioavailability considerations is essential for designing effective drug delivery systems and optimizing product performance. Researchers and formulators continue to explore and innovate in this field to harness the potential of multiple emulsions for improved therapeutic outcomes and product development in various industries.

[PPT] Multiple Emulsions – Types, Preparation and Applications”


Contents of the powerpoint on Multiple Emulsions include:
INTRODUCTION
TYPES OF MULTIPLE EMULSIONS
PREPARATION OF MULTIPLE EMULSIONS
IN VITRO CHARACTERIZATION
STABILITY OF MULTIPLE EMULSIONS
APPLICATIONS
CONCLUSION
REFERENCES

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“Unlocking the Potential of Multiple Emulsions: Types, Preparation, Characterization, Stability, and Applications”

Introduction to Multiple Emulsions

Multiple emulsions, a fascinating class of colloidal systems, offer unique advantages in various industries, from pharmaceuticals to cosmetics and food technology. These complex emulsions, often referred to as “W/O/W” (water-in-oil-in-water), are engineered structures comprising multiple layers of aqueous and oil phases. In this comprehensive exploration, we delve into the world of multiple emulsions, covering their types, preparation methods, in vitro characterization, stability considerations, and versatile applications.

Types of Multiple Emulsions

Multiple emulsions come in several types, each tailored to specific applications and encapsulation requirements. The primary types include:

W/O/W Multiple Emulsions: In this classic configuration, water droplets are dispersed within oil, which is subsequently enveloped by an outer water phase. This type is ideal for encapsulating hydrophilic compounds while protecting them from the external environment.

O/W/O Multiple Emulsions: In the reverse scenario, oil droplets are surrounded by water, forming a water-in-oil-in-water emulsion. This type is suitable for entrapping lipophilic substances within an aqueous medium.

S/O/W and S/W/O Multiple Emulsions: These specialty emulsions incorporate a solid phase (S) in addition to the aqueous and oil phases, expanding their applications in controlled release and encapsulation.

Preparation of Multiple Emulsions

Multiple emulsions can be prepared using various techniques, offering control over their composition and structure:

Two-Step Emulsification: This method involves creating a primary emulsion, typically a water-in-oil (W/O) emulsion, followed by the addition of an outer aqueous phase to form the final water-in-oil-in-water (W/O/W) multiple emulsion.

Phase Inversion Methods: These techniques induce phase inversion between W/O and O/W emulsions by altering factors like temperature or the addition of co-surfactants. This approach provides versatility in emulsion design.

In Vitro Characterization of Multiple Emulsions

Characterization is crucial for understanding the properties and behavior of multiple emulsions. In vitro characterization methods include:

Microscopy: Optical and electron microscopy enable visualizing the internal structure, including droplet size and distribution.

Particle Size Analysis: Techniques like dynamic light scattering (DLS) assess droplet size distribution, influencing stability and performance.

Rheology: Measuring viscosity and flow behavior helps determine the emulsion’s physical properties.

Zeta Potential: Assessing surface charge aids in predicting stability, as droplets with varying charges may repel or attract each other.

Stability of Multiple Emulsions

Stability is a critical aspect of multiple emulsions due to their intricate structure. Factors affecting stability include:

Ostwald Ripening: The growth of larger droplets at the expense of smaller ones over time, potentially causing instability.

Flocculation and Creaming: Aggregation and vertical migration of droplets can lead to phase separation.

Coalescence: The merging of adjacent droplets may result in the formation of larger droplets and eventual phase separation.

Applications of Multiple Emulsions

Multiple emulsions find diverse applications across industries, including:

Pharmaceuticals: Controlled drug delivery systems, enhancing drug solubility, and targeted therapies.

Cosmetics: Encapsulation of active ingredients, improving skin care and cosmetics products.

Food Technology: Enhanced flavor and aroma delivery, controlled release of nutrients, and improved food product quality.

Biotechnology: Encapsulation of enzymes and biologically active compounds for various applications.

Agriculture: Controlled release of fertilizers and pesticides for improved crop yield and sustainability.

Environmental Remediation: Delivery of remediation agents for cleaning up contaminated sites.

In summary, multiple emulsions are versatile systems with a wide range of applications, underpinned by their unique structure and properties. Understanding their types, preparation methods, characterization techniques, stability considerations, and diverse applications is crucial for harnessing their potential across industries.