ANATOMY & PHYSIOLOGY Of Human Respiratory Tract

ANATOMY & PHYSIOLOGY Of Human Respiratory Tract

Anatomy and Physiology Of human respiratory system is a complicated organ system of very close structure– function relationships. The system consisted of two regions: the conducting airway and the respiratory region. The airway is further divided into many folds: nasal cavity and the associated sinuses, and the nasopharynx, oropharynx, larynx, trachea, bronchi, and bronchioles. The respiratory region consists of respiratory bronchioles, alveolar ducts, and alveolar sacs.

ANATOMY AND PHYSIOLOGY OF HUMAN RESPIRATORY TRACT:

               The respiratory system works with the circulatory system to deliver oxygen from the lungs to the cells and remove carbon dioxide, and return it to the lungs to be exhaled. The exchange of oxygen and carbon dioxide between the air, blood and body tissues is known as respiration. Healthy lungs take in about 1 pint of air about 12–15 times each minute. All of the blood in the body is passed through the lungs every minute. The respiratory tract is divided into two main parts: the upper respiratory tract, consisting of the nose, nasal cavity and the pharynx; and the lower respiratory tract consisting of the larynx, trachea, bronchi and the lungs The trachea, which begins at the edge of the larynx, divides into two bronchi and continues into the lungs. The trachea allows air to pass from the larynx to the bronchi and then to the lungs. The bronchi divide into smaller bronchioles which branch in the lungs forming passageways for air. The terminal parts of the bronchi are the alveoli. The alveoli are the functional units of the lungs and they form the site of gaseous exchange     

ANATOMY & PHYSIOLOGY Of Human Respiratory Tract

            The blood barrier between the alveolar space and the pulmonary capillaries is very thin to allow for rapid gas exchange. During inspiration, oxygen diffuses through the alveoli walls and the interstitial space, into the blood. Carbon dioxide diffuses in the opposite direction during exhalation. Alveoli are small and there are approximately 300 million of them in each lung. Although alveoli are tiny structures, they have a very large surface area in total (~100 m2) for performing efficient gas exchange.

                     The alveoli form a honeycomb of cells around the spiral, cylindrical surface of the alveolar duct. The exposed alveolar surface is normally covered with a surface film of lipoprotein material.

                      There are several types of pulmonary alveolar cells. Type I (or small type A), are non-phagocytic, membranous pneumocytes. These surface-lining epithelial cells are approximately 5 μm in thickness and possess thin squamous cytoplasmic extensions that originate from a central nucleated portion. These portions do not have any organelles and hence they are metabolically dependent on the central portion of the cell. This reduces their ability to repair themselves if damaged. Attached to the basement membrane are the larger alveolar cells (Type II, type B or septal cells). These rounded, granular, epithelial pneumocytes are approximately 10 to 15 μm tick. There are 6 to 7 cells per alveolus and these cells possess great metabolic activity. They are believed to produce the surfactant material that lines the lung and to be essential for alveolar repair after damage from viruses or chemical agents.

             Amongst, the important roles of the lungs, one can cite: (i) supply oxygen, (ii) remove wastes and toxins, and (iii) defend against hostile intruders. The lungs have three dozen distinct types of cells. Some of these cells scavenge foreign matter. Others have cilia that sweep the mucous membranes lining the smallest air passages. Some cells act on blood pressure control, while others spot infection invaders.

 anatomy of lungs            

      The respiratory system is susceptible to a number of diseases, and the lungs are prone to a wide range of disorders caused by genetic factors, infection and pollutants in the air. The most common problems of the respiratory system are:

  • Asthma
  • Bronchiolitis
  • Chronic obstructive pulmonary disease (COPD)
  • Common cold
  • Cough
  • Cystic fibrosis (CF)
  • Lung cancer
  • Pneumonia
  • Pulmonary hypertension

PRINCIPAL MECHANISMS OF RESPIRATORY DEPOSITION

            The deposition of inhaled particles in the different regions of the respiratory system is very complex, and depends on many factors. Some of the factors influencing respiratory deposition include:

  • Breathing rate
  • Mouth or nose breathing
  • Lung volume
  • Respiration volume
  • Health of the individual
  • Bifurcations in the airways result in a constantly changing hydrodynamic flow field.

Depending on the particle size, airflow, and location in the respiratory system, particle deposition occurs via on of the following principal mechanisms:

Impaction

         Each time the airflow changes due to a bifurcation in the airways, the suspended particles tend to travel along their original path due to inertia and may impact on an airway surface. This mechanism is highly dependent on aerodynamic diameter, since the stopping distance for very small particles is quite low. Impaction occurs mostly in the case of larger particles that are very close to airway walls, near the first airway bifurcations. Therefore, deposition by impaction is greatest in the bronchial region. Impaction accounts for the majority of particle deposition on a mass basis.

 Sedimentation

           Sedimentation is the settling out of particles in the smaller airways of the bronchioles and alveoli, where the air flow is low and airway dimensions are small. The rate of sedimentation is dependent on the terminal settling velocity of the particles, so sedimentation plays a greater role in the deposition of particles with larger aerodynamic diameters. Hygroscopic particles may grow in size as they pass through the warm, humid air passages, thus increasing the probability of deposition by sedimentation.

 Interception

            Interception occurs when a particle contacts an airway surface due to its physical size or shape. Unlike impaction, particles that are deposited by interception do not deviate from their air streamlines. Interception is most likely to occur in small airways or when the air streamline is close to an airway wall. Interception is most significant for fibers, which easily contact airway surfaces do to their length. Furthermore, fibers have small aerodynamic diameters relative to their size, so they can often reach the smallest airways.

 

 

Diffusion

Diffusion is the primary mechanism of deposition for particles less than 0.5 microns in diameter and is governed by geometric rather than aerodynamic size. Diffusion is the net transport of particles from a region of high concentration to a region of lower concentration due to Brownian motion. Brownian motion is the random wiggling motion of a particle due to the constant bombardment of air molecules. Diffusional deposition occurs mostly when the particles have just entered the nasopharynx, and is also most likely to occur in the smaller airways of the pulmonary (alveolar) region, where air flow is low.

 

 Absorption – bioavailability of drugs

Although inhaled drugs have been used for over 50 years to treat airway disease and are in development or being considered for the treatment of many other lung diseases, insulin is at present time the only one representative inhaled drug on the market for systemic disease. Exubera® (insulin human [rDNA origin] inhalation powder is the first diabetes treatment which can be inhaled. Exubera® helps control high blood sugar, works in adults with type 1 diabetes and with type 2 diabetes as well This therapeutic success has lead a number of other companies to investigate and to advance clinical trials as inhaled formulations for systemic applications with a variety of large molecules (leuprolide, a luteinizing hormone-releasing hormone (LHRH) analogue, …). Recent advances in the development of particle technologies and devices now make it possible to formulate, stabilize, and accurately deliver almost any drug to the lungs.

             The pulmonary membrane is naturally permeable to small molecule drugs and to many therapeutic peptides and proteins. The epithelium of the lung, the significant barrier to absorption of inhaled drugs, is thick (50–60 μm) in the trachea, but diminishes in thickness to an extremely thin 0.2 μm in the alveoli. The change in cell types and morphology going from trachea, bronchi, and bronchioles to alveoli is very dramatic. The lungs are for more permeable to macromolecules than any other portal of entry into the body. Some of the most promising therapeutic agents are peptides and proteins, which could be inhaled instead of injected, thereby improving compliance .Particularly, peptides that have been chemically altered to inhibit peptidase enzymes exhibit very high bioavailabilities by the pulmonary route .Indeed, natural mammalian peptides, les than 30 amino acids (somatostatin, vaso active intestinal peptide [VIP], and glucagons), are broken down in the lung by ubiquitous peptidases and have very poor bioavailabilities. Conversely, proteins with molecular weights between 6000 and 50,000 Da are relatively resistant to most peptidases and have good bioavailabilities following inhalation. For larger proteins, the bioavailabilities and absorption mechanisms are not well completely elucidated.

ADVANTAGES OF PULMONARY DRUG DELIVERY SYSTEM

 

  1. The ability to nebulize viscous drug formulations for pulmonary delivery, thereby overcoming drug solubility issues with the ability to use lipid, water or lipid/water emulsions as drug carriers.
  2. Ability to nebulize viscous liquids into droplets in the 2-5μm range regardless of the carrier composition solubility which would allow for a wide range of drug formulation options.
  3. Increased drug delivery efficacy due to size-stable aerosol droplets with reduced

hygroscopic growth and evaporative shrinkage.

  1. Liposomal drug formulations remain stable when nebulized.
  2. Ability to nebulize protein-containing solutions.
  3. For hand held inhaler applications, drug does not need to be emulsified in liquefied nebulizing gas to achieve aerosolization.

{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,
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Filtration equipment pdf

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

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.

 

 

 

HPLC Detectors – Types Comparison Principles {PDF PPT}*

HPLC Detectors - Types Comparison Principles {PDF PPT}*

Here in this article we provide HPLC Detectors – Types Comparison Principles {PDF PPT}*.Different types of HPLC Detectors are given here for you for educational purpose. The HPLC detectors are used to detect the solute present in the eluent comes from the HPLC column. Different HPLC detectors are used in analysis of different types of samples to detect solute having different chemical nature.

HPLC Detectors – Types:

  1. 1. Ultraviolet/visible spectroscopic detectors{UV Detector/ VIS Detector}

    – Fixed Wavelength Detector
    – Variable Wavelength Detector
    – Diode array Detector
    PDA Detector

  2. 2. Refractive-Index Detector

    -Deflection Detector
    -Refractive Detector (Fresnel refractometer)

  3. 3. Evaporative Light Scattering Detector

  4. 4. Multi-Angle Light Scattering Detector

  5. 5. Mass Spectrometer

  6. 6. Conductivity Detector

  7. 7. Fluorescence Detector

  8. 8. Chemiluminescence Detector

  9. 9. Optical Rotation Detector

  10. 10. Electro Chemical Detector

HPLC Detectors Comparision – Best Detectors properties:

Regardless of the principle of operation, an ideal LC detector should have the following properties:
Low drift and noise level (particularly crucial in trace analysis).
High sensitivity.
Fast response.
Wide linear dynamic range (this simplifies quantitation).
Low dead volume (minimal peak broadening).
Cell design which eliminates remixing of the separated bands.
Insensitivity to changes in type of solvent, flow rate, and temperature.
Operational simplicity and reliability.
It should be tuneable so that detection can be optimized for different compounds.
It should be non-destructive.

HPLC Detectors Uses:

Most common Detectors of HPLC:

Refractive index
UV/Vis
Fixed wavelength (no longer used)
Variable wavelength
Diode array
Fluorescence

Less common, but important Detectors:

Conductivity
Mass-spectrometric (LC/MS)
Evaporative light scattering

HPLC Detectors - Types Comparison Principles {PDF PPT}*

HPLC Detectors – Types Comparison Principles {PDF PPT}*:

Variable-wavelength UV detectors:

Detectors which allow the selection of the operating wavelength called variable wavelength detectors and they are are particularly useful in three cases:
offer best sensitivity for any absorptive component by selecting an appropriate wavelength;
individual sample components have high absorptivity at different wavelengths and thus, operation at a single wavelength would reduce the system’s sensitivity;

Depending on the sophistication of the detector, wavelength change is done manually or programmed on a time basis into the memory of the system.

Any chemical compound could interact with the electromagnetic field. Beam of the electromagnetic radiation passed through the detector flow-cell will experience some change in its intensity due to this interaction. Measurement of this changes is the basis of the most optical HPLC detectors.
Radiation absorbance depends on the radiation wavelength and the functional groups of the chemical compound. Electromagnetic field depending on its energy (frequency) can interact with electrons causing their excitation and transfer onto the higher energetical level, or it can excite molecular bonds causing their vibration or rotation of the functional group. The intensity of the beam which energy corresponds to the possible transitions will decrease while it is passing through the flow-cell. According to the Lambert-Bear law absorbance of the radiation is proportional to the compound concentration in the cell and the length of the cell.

HPLC Detectors – Types Comparison Principles Power point {PDF PPT}

Multi-Angle Light Scattering Detector:

For the SEC analysis, MW of analyte is estimated from the calibration curve drown using a set of known standards. However, by using a MALS, MW can be determined directly without the need of calibration curve. Also MALS can provide an absolute MW of the analyte with very low detection limit.

Refractive index detectors:

These bulk property detectors are based on the change of refractive index of the eluant from the column with respect to pure mobile phase. Although they are widely used, the refractive index detectors suffer from several disadvantages – lack of high sensitivity, lack of suitability for gradient elution, and the need for strict temperature control (±0.001 °C) to operate at their highest sensitivity. A pulseless pump, or a reciprocating pump equipped with a pulse dampener, must also be employed. The effect of these limitations may to some extent be overcome by the use of differential systems in which the column eluant is compared with a reference flow of pure mobile phase. The two chief types of RI detector are as follows.

Deflection refractometer:

The deflection refractometer, which measures the deflection of a beam of monochromatic light by a double prism in which the reference and sample cells are separated by a diagonal glass divide. When both cells contain solvent of the same composition, no deflection of the light beam occurs; if, however, the composition of the column mobile phase is changed because of the presence of a solute, then the altered refractive index causes the beam to be deflected. The magnitude of this deflection is dependent on the concentration of the solute in the mobile phase.

Fresnel refractometer:

The Fresnel refractometer which measures the change in the fractions of reflected and transmitted light at a glass-liquid interface as the refractive index of the liquid changes. In this detector both the column mobile phase and a reference flow of solvent are passed through small cells on the back surface of a prism. When the two liquids are identical there is no difference between the two beams reaching the photocell, but when the mobile phase containing solute passes through the cell there is a change in the amount of light transmitted to the photocell, and a signal is produced. The smaller cell volume (about 3 ilL) in this detector makes it more suitable for high-efficiency columns but, for sensitive operation, the cell windows must be kept scrupulously clean.

HPLC Detectors – Types Comparison Principles PDF word document {PDF PPT}

Mass Spectrometer:

The analytes are detected based on their MW. The obtained information is especially useful for compound structure identification. However, its use is not limited to structure identification and can be used to quantify very low detection limit of elemental and molecular components.

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Mpharm Practical Lab’s Experiment Manual

Experiments for Mpharm Pharmaceutics (Practical record)

This practical manual consists procedures and reports for the following list of experiments:

  1. PREPARATION AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS  2
  2. PREPARATION AND EVALUATION OF  TRANSDERMAL PATCH OF IBUPROFEN   7
  3. PREPARATION AND EVALUATION OF BUCCAL PATCH   11
  4. VALIDATION OF TABLET COATER   14
  5. VALIDATION OF TABLET PRESS  18
  6. VALIDATION OF LAMINAR AIR FLOW HOOD   24
  7. VALIDATION OF MEMBRANE FILTERS  27
  8. VALIDATION OF HOT-AIR OVEN   30
  9. EFFECT OF PERMEATION ENHANCERS ON DRUG PERMEATION THROUGH BIOLOGICALMEMBRANES  40
  10. VALIDATION OF COATING PAN   42
  11. PREPARATION OF KILLED BACTERIAL VACCINE  50
  12. VALIDATION OF TABLET PUNCHING MACHINE  52
  13. VALIDATION OF ASEPTIC ROOM    58
  14. VALIDATION OF AUTOCLAVE  61
  15. VALIDATION OF TRAY DRYER   64

    Download the entire record in pdf here

    Novel_Drug_Delivery_Systems_part 2_record