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Biopharmaceutical classification system & drug delivery system associated with it

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Biopharmaceutical classification system & drug delivery system associated with it

  1. 1. BIOPHARMACEUTICAL CLASSIFICATION SYSTEM & DRUG DELIVERY BASED ON BCS GUIDED BY PROF. DR. PRAMOD SALVE, UDPS, NAGPUR Prepared by Pratik Shinde Mpharm 1st year, UDPS Nagpur
  2. 2. INDEX 1. 2. 3. 4. 5. 6. 7. 8. 9. INTRODUCTION BIOPHARMACEUTICAL CLASSIFICATION SYSTEM FACTOR AFFECTING BCS BIOWAIVER Method for enhancement of Bioavailability Drug delivery system based on the BCS SEDDS/SMEDDS GRDDS REFERENCE
  3. 3. BIOPHARMACEUTICAL CLASSIFICATION SYSTEM • The Biopharmaceutical Classification System was first developed by in 1995, by Amidon et al & his colleagues. • The Biopharmaceutical Classification System is defined as scientific framework for classifying a drug substance based on its aqueous solubility & intestinal permeability & dissolution rate. • To saved time fast screening is required so drug substances are classified on basis of solubility and permeability. This classification is called Biopharmaceutical Classification System. [1]
  4. 4. FACTOR AFFECTING BCS • There are 3 factor affecting BCS are as follows 1. Solubility 2. Permeability 3. Dissolution • SOLUBILITY The Maximum Amount of solute dissolved in a given solvent under standard conditions of temperature, pressure and pH. [4]
  5. 5. • Permeability 1. Permeability of the drug to pass the biological membrane which is the lipophilic. 2. Permeability is indirectly based on the extent of absorption of a drug substance . 3. Drug substance is considered to be highly permeable, when the extent of absorption in human determined to be 90% or more of administered drug or compare to in vivo reference dose. • Dissolution 1. Dissolution is process in which solid substance solubilise in given solvent i.e mass transfer from solid surface to liquid phase. [4]
  6. 6. • High Solubility – The highest single unit dose is completely soluble in 250 ml or less of aqueous solution at pH 1 – 7.5 (37°C) – 250 ml: derived from typical BE study protocols that prescribe the administration of a drug product to fasting human volunteers with a glass (approx. 250 ml) water • High Permeability – According to HHS-FDA, when 90 % or more of the orally administered dose is absorbed in the small intestine. – Permeability can be assessed by pharmacokinetic studies (for example, mass balance studies), or intestinal permeability methods, e.g. intestinal perfusion in humans, animal models, Caco 2 cell lines or other suitable, validated cell lines. [4]
  7. 7. • Dissolution: – In three different media: pH 1.2 HCl, pH 4.5 Acetate buffer and pH 6.8 Phosphate buffer, composition in a paddle (50 rpm) or basket (100 rpm) apparatus at 37 °C and a volume of 900 ml • Very Rapid Dissolution: – An IR drug product is considered VERY RAPIDLY DISSOLVING when >85% of the labeled amount of drug substance dissolves within 15 minutes • Rapid Dissolution – An IR drug product is considered RAPIDLY DISSOLVING when >85% of the labeled amount of drug substance dissolves within 30 minutes. [4]
  8. 8. BIOPHARMACEUTICAL CLASSIFICATION SYSTEM CLASS SOLUBILITY PERMEABILITY EXAMPLE Class I High High Metaprolol , Propanolol Class II Low High Nifedipine , Naproxen Class III High Low Cimetidine, Metformin Class IV Low Low Taxol , Clorthiazide
  9. 9. HIGH SOLUBILITY, HIGH PERMEABILITY LOW SOLUBILITY, HIGH PERMEABILITY CLASS I • Ideal for oral route administration. • Drug absorbed rapidly. • Drug dissolved rapidly. • Rapid therapeutic action. • Bioavailability problem not expected for immediate release drug product. • e.g. Metoprolol , Propranolol, Diltiazem CLASS II • Oral route for administration. • Drug absorb rapidly. • Drug dissolve slowly. • Bioavailability is controlled by dosage form and rate of release of the drug substance. • e. g. Nifedipine, naproxen.
  10. 10. HIGH SOLUBILITY, LOW PERMEABILITY LOW SOLUBILITY, LOW PERMEABILITY CLASS III • Oral route for administration. • Drug absorbance is limited. • Drug dissolve rapidly. • Bioavailability is incomplete if drug is not release or dissolve in absorption window. • e. g. Cimitidine, Metformin,Insulin. CLASS IV • Poorly absorbed by orally administration. • Both solubility & permeability limitation. • Low dissolution rate. • Slow or low therapeutic action. • An alternate route of administration may be needed. • e. g. Taxol, Chlorthiazole, Cefexime Trihydrate.
  11. 11. APPLICATION • To predict in vivo performance of drug product using solubility and permeability measurements. • Aid in earliest stages of drug discovery research. • To use in biowaiver considerations. • For research scientist to decide upon which drug delivery technology to follow or develop. • Also for the regulation of bioequivalence of the drug product during scale up and post approval.[1]
  12. 12. BIOWAIVER • The term biowaiver is applied to a regulatory drug approval process when the dossier (application) is approved based on evidence of equivalence other than through in vivo equivalence testing. • A biowaiver means that in vivo bioavailability and/or bioequivalence studies may be waived (i.e. not considered necessary for product approval). • In 1995 the American Department of Health and Human Services, US Food and Drug Administration (HHS-FDA) instigated the Biopharmaceutics Classification System (BCS), with the aim of granting so- called biowaivers for SUPACs. [4]
  13. 13. BIOWAIVER • At that time the biowaiver was only considered for SUPAC to pharmaceutical products. • More recently, the application of the biowaiver concept has been extended to approval of certain orally administered generic products • Scope: – Inside a product: • Scale up processes • Line extensions • Variation after marketing authorisation – between different products: • Application of generics without clinical data. [4]
  14. 14. Method for enhancement of Bioavailability • There are 3 basic approaches are for increase in the bioavailability are as follows 1. Pharmaceutical Approach 2. Pharmacokinetic Approach 3. Biological Approach • Objective 1. Enhancement of drug solubility/dissolution rate 2. Enhancement of drug permeability 3. Enhancement of drug solubility 4. Enhancement of gastrointestinal retention. [1]
  15. 15. Pharmaceutical Approach Pharmacokinetic approach Biological approach Modification in the • Formulation • Manufacturing process • Physicochemical properties This approach work by following method • Modification in the chemical structure • Development of new chemical entity • Prodrug Design Biological approach implement the changes in • Route of administration • Solubility • Dissolution Rate • Permeability. [1]
  16. 16. Methods for enhancement of bioavailability of drug by Solubility/ Dissolution rate Permeability 1. Micronisation 2. Nanonisation 3. Super critical fluid recrystallization 4. Spray freeze drying 5. Evaporative precipitation 6. Use of surfactant 7. Use of salt form 8. Precipitation inhibitor 9. Alteration of pH 10.Solvent deposition 11.Selective adsorption 12.Amorphs, hydrate, solvates • Lipid formulation 1. Lipid solutions and suspensions 2. Microemulsion 3. Solid lipid nanoparticle 4. Nanostructured lipid carriers 5. Lipid drug conjugates 6. Liposomes • Ion Pairing • Penetration enhancers 1. Physical e.g. Iontophoresis, Sonophoresis, electroporation 1. Chemical e.g. Surfactants, azones, Pyrrolidones, Sulphoxides.[1]
  17. 17. Methods for enhancement of bioavailability of drug by Drug Stability Gastrointestinal retention • Enteric Coating • Complexation • Metabolism inhibitors 1. Bioadhesive delivery system 2. Controlled release Micro encapsulated system 3. Immobilization of enzyme inhibitor • Development of Gastro retentive drug delivery System • Increased Contact With Epithelial Surfaces • Prolonging residence time in the Stomach • Delaying Intestinal Transit. [1]
  18. 18. Drug delivery system based on the BCs • Dissolution, Permeability and solubility are 3 important factors for all kind delivery system. ( I.E. Oral, Topical, transdermal, Sublingual, Buccal ) • Development of various Novel drug delivery system which are as follows, 1. SEDDS (self emulsifying drug delivery system) 2. SMEDDS (self micro-emulsifying drug delivery system) 3. GRDDS (Gastro retentive drug delivery system) 4. Bioadhesive drug delivery system [1]
  19. 19. SEDDS / SMEDDS  Concept introduced by Hoar and Schulman in 1940’s who generated a clear single phase solution by titrating a milky emulsion with hexanol.  Alternative names for these systems are often used, such as transparent emulsion, swollen micelle, micellar solution, and solubilized oil.  Schulman and co-worker in 1959 subsequently coined the term Micro emulsion.  Micro emulsions are an isotropic mixture of natural or synthetic oils, solid or liquid surfactants, co-surfactant and drugs.  Upon mild agitation followed by dilution in aqueous media, such as gastrointestinal (GI) fluids, the system can form fine oil in water (O/W) micro emulsions which usually have droplet size less than 100 nm.  Micro emulsion have been successively used to improve the solubility, chemical stability and oral bioavailability of poorly water soluble drugs.  class II & IV as per BCS classification.[3]
  20. 20. SEDDS SELF EMULSIFYING DRUG DELIVERY SYSTEM SMEDDS SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEM 1. It is the mixture of oil, surfactant and drug. 2. Droplet size is 100-300 nm 3. It is turbid in nature. 4. It is thermodynamically not stable. 5. Ternary phase diagram are used in optimization.. 1. It is a mixture of oil, surfactant, co- surfactant and drug 2. Droplet size is less than 100 nm. 3. It is transparent in nature. 4. It is thermodynamically stable. 5. Pseudo Ternary Phase diagram are used for optimization.[3]
  21. 21. ADVANTAGES DISADVANTAGES 1. Enhanced oral bioavailability and AUC enabling reduction in dose 2. More consistent temporal profile of drug absorption 3. Selective drug targeting towards specific absorption window in GIT 4. Protection of sensitive drug from hostile environment in gut 5. Fine oil droplets empty rapidly from the stomach and promote wide distribution of drug throughout the intestinal tract at short time period 6. Ease of manufacture and scale up 7. Potential to deliver peptides that are processed to enzymatic hydrolysis in GIT. 8. Useful for both solid and liquid dosage form 1. Lack of good predicative in vitro models for assessment of the formulation. 2. In-vitro model needs further development and validation 3. Different prototype lipid based formulations need to be developed and tested in vivo in a suitable animal model. [3]
  22. 22. Gastro-retentive drug delivery system • Oral route is extensively used, but not all drugs are uniformly absorbed throughout GIT. • Drugs released after absorption window has no or negligible absorption. This can be overcome by retaining drug in stomach. • Gatro rententive drug delivery (GRDDS) is one of the site specific drug delivery for the delivery of drugs at stomach. • It is obtained by retaining dosage form into stomach and drug is being released at controlled manner at specific site. • GRDDS is an approach to prolong gastric residence time, there by targetting site specific drug release in the upper gastrointestinal tract (GIT) for local and systemic effect. 3COPS DSU Department of Pharmaceutics. • In GRDDS, Class 2 drugs.[2]
  23. 23. Appropriate candidate for GRDDS • Drugs acting locally in the stomach. – e.g. Antacids and drugs for H. Pylori viz., Misoprostol • Drugs that are primarily absorbed in the stomach. – e.g. Amoxicillin • Drugs that is poorly soluble at alkaline pH – e.g. Furosemide, Diazepam, Verapamil etc. • Drugs with a narrow window of absorption – e.g. Cycloserine, Methotrexate, Levodopa etc. • Drugs which are absorbed rapidly from the GIT – e.g. Metronidazole, tetracycline. • Drugs that degrade in the colon. – e.g. Ranitidine, Metformin HCl. • Drugs that disturb normal colonic microbes. – e.g. antibiotics
  24. 24. Drug candidates not suitable for GRDDS • Drugs that have very limited acid solubility. – E.g. Phenytoin • Drugs that suffer instability in the gastric environment. – E.g. Erythromycin • Drugs intended for selective release in the colon. – E.g. 5-Amino salicylic acid and corticosteroids, etc. • Drugs having extensive first pass metabolism. [2]
  25. 25. FACTORS AFFECTING THE GRDDS 1. Density 2. Size and Shape of the dosage form 3. Single or Multi unit formulation 4. Age 5. Gender 6. Body posture 7. Frequency of intake 8. Diseased state of an individual. [2]
  26. 26. ADVANTAGES DISADVANTAGES 1. Improved drug absorption because of increased GRT. 2. Enhanced bioavailability. 3. Controlled drug delivery. 4. Reduced dosing frequency. 5. Ease of administration. 6. Better patient compliance. 7. Targeted therapy for local ailments in the upper GIT. 8. Reduced fluctuations of drug concentration. 9. Delivery of drugs with narrow absorption window in small intestine region. 1. Retention in stomach is not desirable for drugs that cause gastric lesions/irritations. e.g. NSAIDS. 2. Drugs degraded in the acidic environment of stomach. e.g. insulin. 3. Drugs undergo significant first- pass metabolism. e.g. nifedipine. 4. Drugs have limited acid solubility. e.g.phenytoin. 5. These systems require a high level of fluid in the stomach for drug delivery to float and work efficiently. 6. These systems do not offer significant over the conventional dosage forms for drugs, which are absorbed throughout GIT. [2]
  27. 27. EVALUATION PARAMETERS Pre- compression test Post compression test 1. Size and shape 2. Particle size 3. Density 4. Specific gravity 5. Flow properties 1. Thickness and diameter 2. Hardness and friability 3. Weight variation test 4. floating time 5. Content uniformity 6. Dissolution test 7. Mucoadhesive test
  28. 28. IN VITRO TEST IN VIVO TEST 1. Floating lag time 2. Floating time 3. Dissolution study 4. Swelling index 5. Muco adhesive test 6. Density 1. Radiology 2. Scintigraphy 3. Gastroscopy 4. Magnetic marker monitoring 5. Ultrasonography. [2]
  29. 29. APPLICATION  Enhanced bioavailability  Sustained drug delivery  Site specific drug delivery system  Absorption enhancement  Minimized adverse activity at the colon  Reduced fluctuation of drug concentration. [2]
  30. 30. REFERENCE 1. D.M.BRAMHANKAR, SUNIL B. JAISWAL AND A, TREATISE, BIOPHARMACEUTICS AND PHARMACOKINETICS, VALLABH PRAKASHAN, PITAMPURA, DELHI 2. https://www.slideshare.net /ArpithaAarushi/ gastroretentive-drug-delivery-system- 182221356 3. https://www.slideshare.net /HimalBarakoti/ self- microemulsifying-drug-delivery-system-smedds 4. https://www.slideshare.net/axmedaxundov/biowaive r-52456485
  31. 31. THANK YOU

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