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Pharmaceutical Technology


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Biopharmaceutic Classification System(BCS) of drugs & Tablet formulation

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Pharmaceutical Technology

  1. 1. Pharmaceutical Technology-II Assignment on : Biopharmaceutic Classification System(BCS) of drugs & Tablet formulation Submitted to : Mr. Md. Saiful Islam Pathan Associate Professor, Department of Pharmacy State university of Bangladesh 1 Submitted by : Md. Reyaz Ahamed(UG08-21-12-007) Tasmia Tabassum(UG08-21-12-003) State University of Bangladesh. (Department of Pharmacy ).Batch: 21 A
  2. 2. Biopharmaceutics Classification System (BCS) Biopharmaceutics is concerned with factors that influence the rate of drug absorption. The factors that affect the - - release of a drug from its dosage form, - its dissolution into physiological fluids, - its stability within those fluids, - its permeability across the biological membrane and - its presystemic metabolism will influence its rate and extent of absorption. Once the drug is absorbed into the systemic circulation , its distribution within the body tissue (including to its site of action), its metabolism and elimination are described by the pharmacokinetics of the compound. 2
  3. 3. The key biopharmaceutical properties that can be quantified and therefore give an insight into the absorption of a drug are its: Release of drug from its dosage form into solution at the absorption site. Stability in physiological fluids. Permeability across the biological membrane. Presystemic metabolism. 3
  4. 4. Introduction of Biopharmaceutics Classification System (BCS) The Biopharmaceutics Classification System (BCS) is a scientific framework for classifying drug substances based on their aqueous solubility and intestinal permeability. The principle of the BCS is that if two drug products yield the same concentration profile along the gastrointestinal (GI) tract, they will result in the same plasma profile after oral administration. This concept can be summarized by the following equation: J = PwCw where, J is the flux across the gut wall, Pw is the permeability of the gut wall to the drug and Cw is the concentration profile at the gut wall. 4
  5. 5. According to BCS, drug substances or APIs are divided into high/low solubility and permeability classes as follow: Class I : High Solubility - High Permeability Class II : Low Solubility - High Permeability Class III : High Solubility - Low Permeability Class IV : Low Solubility - Low Permeability 5
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  7. 7.  Class I drugs exhibit a high dissolution number & high absorption number . That’s why this drugs rapidly transported across the gut wall. e.g. β – blockers(propranolol & metaprolol).  Class II drugs have a low dissolution number but a high absorption number . The absorption for Class II drugs is usually slower than Class I and occurs over a longer period of time. e.g. Non-steroidal anti-inflammatory drugs.  Class III drugs, dissolve rapidly but which are slow to permeate the gastrointestinal epithelium, are in contact with it. e.g. H2-antagonist & β-blocker(atenolol) .  Class IV drugs are those that are classed as poorly soluble & poorly permeable. They have a poor oral bioavailability. That’s why they can not given by the oral route. e.g. Thiazide diuretics. 7
  8. 8. Table : Examples of some drugs as per biopharmaceutical classification system 8
  9. 9. Class Boundaries: The drugs are classified in BCS on the basis of following parameters: 1. Solubility 2. Permeability 3. Dissolution 9
  10. 10. The class boundaries for these parameters are: 1. Solubility class boundaries- It is based on the highest dose strength of an immediate release (IR) product. A drug is considered highly soluble when the highest dose strength is soluble in 250 ml or less of aqueous media over the pH range of 1 to 7.5. 2. Permeability class boundaries- A drug substance is considered highly permeable when the extent of absorption in humans is determined to be 90% or more of the administered dose based on a mass-balance determination or in comparison to an intravenous dose. 10
  11. 11. 3. Dissolution class boundaries- A drug product is considered to be RAPIDLY DISSOLVING when > 85% of the labeled amount of drug substance dissolves within 30 minutes using USP dissolution apparatus I or II in a volume of 900 ml or less in the following media:  0.1 N HCl or simulated gastric fluid or  Mix phosphate buffer pH 6.8 or simulated intestinal fluid. 11
  12. 12. Tablet Formulation 12
  13. 13. Introduction of Tablets Definition: Tablets are defined as unit dose, solid preparations containing one or more active ingredients. Tablets are obtained by compressing uniform volumes of particles. Most of time powders must be converted to granules. 13
  14. 14.  They are mainly intended for oral administration.  Some are Swallowed whole (Conventional)  Some are being chewed (Chewable)  Some are dissolved or dispersed in water before being administered (Dispersible/Effervescent)  Some are retained in the mouth, where the active ingredient is 'liberated'. (Buccal & Sublingual) 14
  15. 15. Advantages of Tablets  Tablets are convenient to use and are an elegant dosage form.  Offers a range of drug release rates and durations of clinical effect.  Tablets may be formulated to offer rapid drug release or controlled drug release.  Gives formulator choice to release the therapeutic agent at a particular site within the gastrointestinal tract - To reduce side effects. - To promote absorption at that site and. -To provide a local effect. 15
  16. 16.  Physical or chemical incompatible active pharmaceutical substances can be incorporated.  Easier to mask the taste of bitter drugs.  The chemical, physical and microbiological stability.  Inexpensive dosage form. Production aspect  Large scale production at lowest cost.  Easiest and cheapest to package and ship.  High stability. User aspect (doctor, pharmacist, patient)  Easy to handling.  Lightest and most compact.  Greatest dose precision & least content variability.  Coating can mask unpleasant tastes & improve patient acceptability. 16
  17. 17. Disadvantages of Tablets  It requires a series of unit operations, causing increased level of product loss.  The absorption dependent on physiological factors, e.g. gastric emptying rate, and shows inter patient variation.  The compression properties of certain therapeutic agents are poor.  Impose problem for administering in children and the elderly difficulties in swallowing.  In case of unconscious patient it can not be administered. 17
  18. 18.  Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability.  Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating. 18
  19. 19. Types of Tablets On the basis of coating, tablet may be- 1. Uncoated or 2. Coated Uncoated Tablets:  chewable tablet,  effervescent tablet,  lozenge tablet,  soluble tablet and  sublingual tablet. 19 Coated tablets:  enteric coated tablet,  film coated tablet,  implant,  sugar coated tablet and  modified-release tablet.
  20. 20. 20 On the basis of Route of administration  Oral tablets  Sublingual or buccal tablets  Vaginal tablets On the basis of Production process  Compressed tablets  Multiple compressed tablets  Tablet within a tablets: core and shell  Multilayer tablet
  21. 21. Additives used in tablets  Drugs (Active pharmaceutical ingredient (API): Example: paracetamol, aspirin, diclofenac, metformin, telmisartan, nimesulide , nifedipine etc.  Diluents: Act as fillers used to make required bulk of the tablet. A diluent should have following properties:  Non toxic  Commercially available in acceptable grade  Low in cost  Physiologically inert 21
  22. 22.  Physically & chemically stable by themselves & in combination with the drugs.  Free from all microbial contamination.  Do not alter bioavailability of drug.  Color compatible Commonly used tablet diluents: • Microcrystalline cellulose-Avicel (PH 101 and PH 102) • Dibasic calcium phosphate dehydrate • Calcium sulphate dihydrate • Mannitol • Sorbitol • Sucrose • Dextrose, etc. 22
  23. 23.  Binders: Binders hold the ingredients in a tablet together Examples: Acacia, tragacanth,Cellulose derivatives- MC, HPC, HPMC(Hydroxypropyl methylcellulose). Gelatin, Glucose,Polyvinylpyrrolidone (PVP), Starch paste, Sodium alginate , sorbitol , etc.  Disintegrants Added to facilitate disintegration when comes in contact with water in the GIT. Example: Starch, Cellulose derivatives- CMC-Na (sodium carboxy methyl cellulose), PVP (Polyvinylpyrrolidone) 23
  24. 24.  Lubricants Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Example: Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycol), Surfactants.  Glidants Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles. Example: Corn Starch , Talc , Silica 24
  25. 25.  Antiadherants Reduce the adhesion between the powder (granules) and the punch faces and thus prevent tablet sticking to the tablet Punches. e.g. Magnesium stearate, Talc  Preservatives Examples: Citric acid and sodium citrate, methyl and propyl paraben.  Coloring agents: Example: FD & C color.  Flavoring agents: For chewable tablet- flavor oil are used  Sweetening agents: For chewable tablets: Sugar, mannitol. 25
  26. 26. 26
  27. 27. 27 The main process of tablet formulation is granulation. Granulation A size enlargement process which converts small particles into physically stronger & larger agglomerates. Granulation method can be broadly classified into two types:  Wet granulation  Dry granulation
  28. 28. Pharmaceutical Granulation Equipment Wet granulators: There are three main types of granulator used in the pharmaceutical industry for wet granulation.  Shear granulators  High-speed mixer/granulators  Fluidized-bed granulators 28
  29. 29. Shear Granulators  The mixed powders are fed into the bowl of the planetary mixer and granulating liquid is added as the paddle of the mixer agitates the powders.  The planetary action of the blade when mixing is similar to that of a household mixer 29
  30. 30. High-speed mixer/granulators  This type of granulator (e.g. Diosna, Fielder) is used extensively in pharmaceutics.  The machines have a -Stainless steel mixing bowl containing a three-bladed main impeller, which revolves in the horizontal plane, -Three-bladed auxiliary chopper (breaker blade) which revolves either in the vertical or the horizontal plane.  The unmixed dry powders are placed in the bowl and mixed by the rotating impeller for a few minutes.  Granulating liquid is then added via a port in the lid of the granulator while the impeller is turning.  The granulating fluid is mixed into the powders by the impeller. 30
  31. 31.  The chopper is usually switched on when the moist mass is formed, as its function is to break up the wet mass to produce a bed of granular material. 31
  32. 32. 32 Figure: High-speed mixer/granulators
  33. 33. Fluidized-bed granulators  The powder particles are fluidized in a stream of air, but in addition granulation fluid is sprayed from a nozzle on to the bed of powders.  Heated and filtered air is blown or sucked through the bed of unmixed powders to fluidize the particles and mix the powders; fluidization is actually a very efficient mixing process.  Granulating fluid is pumped from a reservoir through a spray nozzle positioned over the bed of particles.  The fluid causes the primary powder particles to adhere when the droplets and powders collide.  Escape of material from the granulation chamber is prevented by exhaust filters, which are periodically agitated to reintroduce the collected material into the fluidized bed. 33
  34. 34. 34
  35. 35. Dry granulators Sluggers:  Dry powders can be compressed using a conventional tablet machine or, more usually, a large heavy duty rotary press can be used.  This process is often known as 'slugging',  A hammer mill is suitable for breaking the compacts. Roller compactors:  Powder mix being squeezed between two rollers to form a compressed sheet  The sheet normally is weak and brittle and breaks immediately into flakes.  These flakes need gentler treatment to break them into granules, and this can usually be achieved by screening alone. 35
  36. 36. Figure: Dry granulators 36
  37. 37. Methods of tablet manufacture There are three basic methods of preparation of compressed tablets.  Wet granulation  Dry granulation  Direct compression 37
  38. 38. Unit Operation Wet granulation Dry granulation Direct compression 1. Dispensing/Weighing Dispensing/Weighing Dispensing/Weighing 2. Sieving/Milling Sieving/Milling Sieving/Milling 3. Dry powder mixing Dry powder mixing/Lubrication Dry powder mixing/Lubrication 4. Wet massing with addition of granulating fluid Roller compaction/Slugging Compression 5. Wet screening Milling/Crushing 6. Drying Compression 7. Dry screening after checking LOD 8. Lubrication 9. Compression 38
  39. 39. Tablet manufacturing Four basic requirements for successful tablet production:  Design  Equipments  Facility  Personnel 39
  40. 40. Tablet manufacturing(contd….)  Tablets are made by compressing a formulation containing drug or drugs with excipients on stamping machine called Presses.  Tablet compression machines are designed with following basic components.  Hopper- for holding and feeding granulation to be compressed.  Dies- that define size and shape of tablets.  Punches- for compressing granulation within die.  Cam tracks- for guiding movement of punches.  Feeding mechanism- for moving granules from hopper in to die. 40
  41. 41. Tablet manufacturing(contd….)  Tablet presses are classified as either  Single punch or  Multi station rotary presses. Single punch machine are called as stamping press as all of the compression force is applied by upper punch. Multi-station presses are termed rotary because the head of tablet machine that holds upper punches , dies and lower punch in press rotates.  The ultimate test of a tablet formulation and granulation process is whether the granulation can be compressed on a high-speed tablet press. 41
  42. 42. Figure: Single punch presses 42
  43. 43. Figure: Multi station rotary presses. 43
  44. 44. Tablet manufacturing(contd….)  During compression, the tablet press performs the following functions:  Filling of empty die cavity with granules.  Precompression of granulation (optional).  Compression of granules.  Ejection of the tablet from the die cavity and take-off of compressed tablet. 44
  45. 45. Thank you 45