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Department of pharmaceutics

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1 Department of pharmaceutics
Biopharmaceutics classification system , methods of permeability generic biologics , Bioequivalence and bioavailability and generic substitution Department of pharmaceutics Prepared by: Siddhapura Pratik M.Pharm (sem-2) Siddhapura Pratik ( M.Pharm Pharmaceutics)

2 CONTENT Biopharmaceutics classification system
Methods of Permeability: In-vitro, In-situ and In-vivo methods Generic biologics (biosimilar drug products) Clinical significance of bioequivalence studies Special concerns in bioavailability and bioequivalence studies Generic substitution Siddhapura Pratik ( M.Pharm Pharmaceutics)

3 Biopharmaceutics classification system
1.1 Introduction 1.2 Factor affecting on biopharmaceutical classification system 1.3 Biopharmaceutical classification system [Classes] 1.4 Application of biopharmaceutical classification system 1.5 Class boundaries 1.6 Biowaiver 1.7 Criteria of biowaiver 1.8 Conclusion Siddhapura Pratik ( M.Pharm Pharmaceutics)

4 1.1 Introduction The Biopharmaceutical Classification system was first developed in 1995, by Amidon et & his colleagues. Definition: “The biopharmaceutical classification system is a 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 as Biopharmaceutical classification system. Siddhapura Pratik ( M.Pharm Pharmaceutics)

5 1.2 Factor affecting on biopharmaceutical classification system
The biopharmaceutical classification system has been developed to provide A scientific approach to allow for to prediction in vivo pharmacokinetics of oral immediate release (IR) drug product by classifying drug compound based on their. Solubility Permeability Dissolution Siddhapura Pratik ( M.Pharm Pharmaceutics)

6 Solubility The maximum amount of solute dissolved in a given solvent under standard condition of temperature, pressure and pH. Solubility is the ability of the drug to be solution after dissolution. The higher single unit dose is completely soluble in 250 ml at pH (37 ̊C). Siddhapura Pratik ( M.Pharm Pharmaceutics)

7 Permeability Permeability of the drug to pass the biological membrane which is the lipophilic. Permeability is indirectly based on the extent of absorption of a drug substance. 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. Siddhapura Pratik ( M.Pharm Pharmaceutics)

8 Dissolution It is process in which solid substance solubility in given solvent i.e mass transfer from solid surface to liquid phase. Using USP apparatus I at 100 rpm or USP apparatus II at 50 rpm. Dissolution media [900 ml]. 0.1 N HCl or simulated gastric fluid (pH 1.2) without enzyme. pH 4.5 buffer & pH 6.8 buffer. Simulated intestinal fluid without enzyme. Siddhapura Pratik ( M.Pharm Pharmaceutics)

9 1.3 Biopharmaceutical classification system [Classes]
Siddhapura Pratik ( M.Pharm Pharmaceutics)

10 Siddhapura Pratik ( M.Pharm Pharmaceutics)

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12 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. Siddhapura Pratik ( M.Pharm Pharmaceutics)

13 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. Siddhapura Pratik ( M.Pharm Pharmaceutics)

14 Class III Oral route of administration. Drug absorbance is limited.
Drug dissolve rapidly. Bioavailability is incomplete if drug is not release or dissolve in absorption window. E.g. cimetidine, metformin , insulin. Siddhapura Pratik ( M.Pharm Pharmaceutics)

15 Class IV Poorly absorbed 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. Siddhapura Pratik ( M.Pharm Pharmaceutics)

16 1.4 Application of biopharmaceutical classification system
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. Siddhapura Pratik ( M.Pharm Pharmaceutics)

17 1.5 Class boundaries Highly soluble
The highest dose strength is soluble in ≤250 ml water over a pH range of 1 to 7.5. The volume estimate – a glassful ( 8 ounce) Highly permeable When the extent of absorption in humans is determined to be ≥ 90% of an administered dose. Rapidly dissolving When ≥ 85% of the labelled amount of drug substance dissolves within 30 minutes using USP apparatus I to II in a volume of ≤ 900ml buffer solutions. Siddhapura Pratik ( M.Pharm Pharmaceutics)

18 1.6 Biowaiver “in vitro instead of in vivo bioequivalence testing”
Definition: It is an exemption from conducting human bioequivalence studies when the active ingredients meet certain solubility and permeability criteria in vitro and when the dissolution profile of the dosage from meets the requirements for an IR dosage form. Siddhapura Pratik ( M.Pharm Pharmaceutics)

19 1.7 Criteria of biowaiver Rapid and similar dissolution
High solubility High permeability Wide therapeutic window Excipient used in dosage form are same as those present in approved drug product Siddhapura Pratik ( M.Pharm Pharmaceutics)

20 1.8 Conclusion Biopharmaceutical classification system aims to provide regulatory tools for replacing certain bio-equivalence studies by a accurate in vivo dissolution tests. The in vivo pharmacokinetics of drug depends largely on the solutility and permeability. Many laboratories are engaged to find better means to estimates in vivo behaviour of the drug after oral administration by using simple in vitro dissolution tests. Siddhapura Pratik ( M.Pharm Pharmaceutics)

21 2.Methods of permeability
In Vitro In Situ In Vivo Siddhapura Pratik ( M.Pharm Pharmaceutics)

22 IN VITRO METHOD In vitro method are carried out outside of the body and are used to determine the permeability of drug using live animal tissues. In vitro models have been introduced to assess to the major factors involved in the absorption process and predict the rate and extent of drug absorption. Here, the intestine of lower experimental animals such as rats , guinea pigs, rabbits are taken for the study. Siddhapura Pratik ( M.Pharm Pharmaceutics)

23 The different in vitro methods are:
Physicochemical methods Partition coefficient Artificial membranes Chromatographic retention indices Brush border membrane vesicles (BBMV) Isolated intestinal cells Tissue technique: Everted small intestinal sac technique Everted sac modification Circulation techniques Everted intestinal ring or slice techniques diffusion cell method Cell culture techniques. Siddhapura Pratik ( M.Pharm Pharmaceutics)

24 1. Partition coefficient
Siddhapura Pratik ( M.Pharm Pharmaceutics)

25 1. Partition coefficient
Siddhapura Pratik ( M.Pharm Pharmaceutics)

26 1. Partition coefficient
Partition coefficient between an oil and water phase , log p, is one of the easiest property of a drug molecule that can be determined. It provides a measure of the lipophilicity of a molecule and can be used to predict to what extent it will cross the biological membrane. Eg. Octanol is selected as an oil phase as it has similar properties to biological membranes. It’s important to note that log p does not take the degree of ionization into consideration and hence log D is used. Siddhapura Pratik ( M.Pharm Pharmaceutics)

27 1. Partition coefficient
Log D is the distribution coefficient where aqueous phase is at a particular pH and thus it takes into account the ionization of the molecule at ths pH. The log D measured at intestinal pH will givea much better idea about extent of drug permeability across GI membrane than log P. Siddhapura Pratik ( M.Pharm Pharmaceutics)

28 2. ARTIFICAL MEMBRANES Artificial membranes are very useful in studying passive membrane permeability as they are reproducible and are suitable for high throughput screening. In this method, PAMPA model is used. Parallel artificial membrane permeability assay (PAMPA) PAMPA is a method which determines the permeability of substances from a donor compartment, through a lipid infused artificial membrane into an acceptor compartment. The artificial membrane is like a phospholipid membranes supported by filter material. It is prepared by pipetting a solution of lipids in an inert organic solvent on a supporting filter material which is placed on 96- well microtitre plate. Siddhapura Pratik ( M.Pharm Pharmaceutics)

29 Procedure test compound is added to the donor compartment in buffer solution of pH 7.4 and permeation takes place through artificial membrane into the acceptor compartment. An aliquot is collected and the concentration of drug permeated is measured by suitable assay technique. Siddhapura Pratik ( M.Pharm Pharmaceutics) Fig. Parallel Artificial Membrane Permeation assay(PAMPA)

30 Uses Advantage Disadvantage Used for screening large no. of compounds.
mainly used to determine the intestinal permeability Prediction of passive transport Trans-cellular permeability of drugs Advantage Used for screening large no. of compounds. Provides information on solubility, lipophilicity and ionization status of a drug. It is much lesser labor intensive than cell culture methods. Disadvantage They are based on approximation and oversimplification of the actual in vivo conditions. Siddhapura Pratik ( M.Pharm Pharmaceutics)

31 A modification of this system
A modification of this system is immobilized liposome chromatography(ILC) and on ILC, many compounds with same log P have been shown to demonstrate variable membrane partitioning based on their logs. Liposomes , lipid bilayers produced from mixture of lipids are also useful in investigating passive diffusion of drugs through lipid membranes and also used to study passive absorption of many monocarboxylic acids. A modified version of this is the filter-immobilized artificial membrane (filter-IAM) permeability assay. This coupled with an instrument PSR4p (Permeability solubility retention, pION, USA) can be used for high throughput permeability screens Siddhapura Pratik ( M.Pharm Pharmaceutics)

32 3. CHROMATOGRAPHIC RETENTION INDICES
Immobilized artificial membranes(IAM) chromatography along with physicochemical parameters is used for evaluation of passive intestinal absorption. IAM packings are prepared by covalently immobilizing monolayers of membrane phospholipids to silica particles. Micellar liquid chromatography(MLC) is also used for the prediction of passive drug absorption and in this system retention of drug mainly depends on hydrophobic, electronic and steric interactions. In general, chromatographic techniques are easy in operation and have high analytical sensitivity. Siddhapura Pratik ( M.Pharm Pharmaceutics)

33 4.BRUSH BORDER MEMBRANE VESICLES (BBMV)
A brush border is the name for the microvilli covered surface of simple cuboidal epithelium and simple columnar epithelial cells, found in the small intestine. Both animal and human tissue can be used for this. Procedure: intestinal tissues are treated with calcium chloride precipitation method using centrifugation. the pellets obtained after centrifugation is resuspended in buffer which results in the formation of vesicles. Siddhapura Pratik ( M.Pharm Pharmaceutics)

34 Fig.1: Brush border membrane vesicles Fig.2: Structure of microvilli
Siddhapura Pratik ( M.Pharm Pharmaceutics)

35 Vesicles are mixed with drug in buffer solution and filtered after a period of time
The amount of drug taken up by the vesicles gives an account of drug absorption. Advantage useful for mechanic studies of drug absorption process. Siddhapura Pratik ( M.Pharm Pharmaceutics)

36 5. USING ISOLATED INTESTINAL CELLS
Here, the small intestine is perfused with enzyme solutions that release the cells and the cells are treated with chelating agents or enzymes. The freshly isolated cells are suspended in buffer solution. At the time of experiment, the cells are separated, resuspended in buffer containing the drug under O2/CO2 and shaken well. After a specific period of time, the cells are separated by filtration, extracted and drug absorbed is determined. Siddhapura Pratik ( M.Pharm Pharmaceutics)

37 a). Everted small intestinal sac technique:
6.TISSUE TECHNIQUES a). Everted small intestinal sac technique: this method involves isolating a small segment of the intestine of a laboratory animal such as rat, inverting the intestine and filling the sac with a small volume of drug free buffer solution. Both the segments are tied off and the sac is immersed in an ERLENMEYER FLASK containing a large volume of buffer solution that contains the drug. The flask and its contents are then oxygenated and the whole preparation is maintained at 37°C and shaken mildly. At predetermined time intervals, the sac is removed and the concentration of drug in the serosal fluid is determined/assayed for drug content. Siddhapura Pratik ( M.Pharm Pharmaceutics)

38 Advantage Disadvantage
-the epithelial cells of the mucosal surface are exposed directly to the oxygenated mucosal fluid. -Prolongs the viability and integrity of the preparation after removal from the animal. -Convenience and accuracy with respect to drug analysis. Disadvantage - Difficulty in obtaining more than one sample per intestinal segment Siddhapura Pratik ( M.Pharm Pharmaceutics)

39 Fig. Everted sac technique
Siddhapura Pratik ( M.Pharm Pharmaceutics)

40 b)- EVERTED SAC MODIFICATION
In this method, the test animal is fasted for a period of hr and water is allowed. The animal is killed and the entire small intestine is everted. Segments, cm in length are cut from a specific region of the intestine. The distal end of the segment is tied and the proximal end is attached to the cannula. The segment is suspended in a mucosal solution which contains the drug. A drug free buffer is then placed in the serosal compartment. Siddhapura Pratik ( M.Pharm Pharmaceutics)

41 Fig. Everted sac modification
For determining the rate of drug transfer, the entire volume of serosal solution is removed from the sac at each time interval with the help of a syringe and replaced with fresh buffer solution. Fig. Everted sac modification Siddhapura Pratik ( M.Pharm Pharmaceutics)

42 Simple and reproducible.
The amount of drug that permeates the intestinal mucosa is plotted against time to describe the absorption profile of drug at any specific pH. Advantage A number of different solutions may be tested with a single segment of the intestine. Simple and reproducible. It distinguishes between active and passive diffusion. It determines the region of small intestine where absorption is optimal, in the case of active transport. Siddhapura Pratik ( M.Pharm Pharmaceutics)

43 - The intestinal preparation is removed from the animal as
Used to study the effect of pH, surface active agents, complexation and enzymatic hydrolysis. Disadvantage - The intestinal preparation is removed from the animal as well as from its normal blood supply. Under these conditions, the permeability characteristics of the membrane are significantly altered. - The rate of transport of drug as determined from the everted sac technique, may be slower than in the intact animal. Siddhapura Pratik ( M.Pharm Pharmaceutics)

44 c). CIRCULATION TECHNIQUES
In this method, small intestine may or may not be everted. This involves isolating either the entire small intestine of small lab animal or a segment and circulating oxygenated buffer containing the drug through the lumen. Drug free buffer is circulated on the serosal side of the intestinal membrane and oxygenated. Absorption rate from the lumen to the outer solution are determined by sampling both the fluid circulating through the lumen and outside. Siddhapura Pratik ( M.Pharm Pharmaceutics)

45 Advantage This method is applicable to kinetic studies of the factors affecting drug absorption. Both surfaces are oxygenated. Eversion is not necessary. Siddhapura Pratik ( M.Pharm Pharmaceutics)

46 d). EVERTED INTESTINAL RING OR SLICE TECHNIQUE
In this technique, the entire small intestine is isolated from the fasted experimental animal and washed with saline solution and dried by blotting with filter paper. The segment is tied at one end and by placing on glass rod it is carefully everted and cut into small rings. The everted intestinal rings are then incubated in drug containing buffer maintained at 37c with constant oxygenation. Under optimal conditions, rings remain viable for up to 2 hours and the transport of drug is stopped by rinsing the rings with ice cold buffer and drying them. Siddhapura Pratik ( M.Pharm Pharmaceutics)

47 Advantage Disadvantage
At selected time interval, the tissue slices are assayed for drug content and expressed as mol/gm/time. Advantage Simple and reproducible. Kinetic studies can be performed. Each animal can act as its own control as many rings can be prepared from each segment of the intestine isolated. Mechanism of drug absorption can be studied by changing the experimental conditions. Disadvantage Extreme care is needed to maintain to viability of the tissue throughout the experiment. tissue needs to be disrupted completely for the determination of drug contents, which complicates the assay procedure. polarity of the absorption cannot be assayed. Siddhapura Pratik ( M.Pharm Pharmaceutics)

48 7. DIFFUSION CELL METHOD In this method, small segments of small intestine are mounted between two glass chambers filled with buffer at 37 C. Diffusion cell consist of two compartments :- Donor compartment - which contains the drug solution and the lower end of which contains the synthetic or natural GI membrane that interfaces with the receptor compartment. Receptor compartment - which contain the buffer solution. Siddhapura Pratik ( M.Pharm Pharmaceutics)

49 Fig. Diffusion cell for studying drug uptake from GIT
Siddhapura Pratik ( M.Pharm Pharmaceutics)

50 8. CELL CUTURE TECHNIQUES
Cell culture is the complex process by which cells are grown under controlled conditions, generally outside their natural environment. In this technique, differentiated cells of the intestine, originating from CaCo2 cells ( cells of carcinoma of colon) are placed on synthetic polycarbonate membrane previously treated with an appropriate material such as collagen which on incubation aids reproduction of cells while not retarding drug permeation characteristics. These models are based on the assumption that passage of drugs across the intestinal epithelium is the main barrier for drugs to reach the circulation. Siddhapura Pratik ( M.Pharm Pharmaceutics)

51 e.g. T84, SW116 and Col115 cell lines.
Human intestinal cell lines are generally divided into four different groups: Type I : These cells differentiate spontaneously under normal culture conditions and hence are polarized (i.e. apical and basolateral surface), form domes, have tight junctions and brush border (eg.Caco-2 cells). Type II : These cells differentiate into enterocytes- type cells only under specific culture conditions e.g. HT29 in presence of glucose, HT29 clone can differentiate into mucus cells. Type III : These cells form domes but do not express any biochemical or morphological markers of differentiated cells. e.g. T84, SW116 and Col115 cell lines. Type IV : These cells do not differentiate. e.g. HCA7 and SE480 cell lines. Siddhapura Pratik ( M.Pharm Pharmaceutics)

52 Fig. CaCo-2 cell monolayer to study drug absorption
Siddhapura Pratik ( M.Pharm Pharmaceutics)

53 CaCo-2 is the most widely used cell line and CaCo-2 are a human colon carcinoma cell line.
The CaCo2(colon cancer cells) cell line is a continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells. Solution of drug is placed on this layer of cultured cells and the system is placed on this layer of cultured cells and the system is placed(R.C) in a bath of buffer solution. The drug that reaches the latter compartment is sampled and analysed periodically. Siddhapura Pratik ( M.Pharm Pharmaceutics)

54 CaCo2 cells express tight junctions, microvilli and a number of enzymes and transporters that are characteristic of enterocytes. CaCo2 monolayer is widely used across the pharmaceutical industry as an in vitro model of the human small intestine mucosa to predict the absorption of orally administered drugs. The correlation between the in vitro apparent permeability across CaCo2 monolayers and the in vivo fraction absorbed is well established. Cell culture models have been employed in the screening of the intestinal permeability of libraries of new drug entities that have been generated through combinatorial chemistry and high throughput pharmacological screening. Siddhapura Pratik ( M.Pharm Pharmaceutics)

55 In vivo methods In vitro and in situ techniques gives us an idea about absorption , but in vivo method gives us an idea about some important factor that influence absorption such as gastric emptying. Intestinal motility and the effects of drugs on the GIT can be determined. The in vivo method can be classified into: Direct method Indirect method Siddhapura Pratik ( M.Pharm Pharmaceutics)

56 Direct method The drug levels in blood or urine is determined as a function of time. For this , a suitable sensitive reproducible analytical procedure should be developed to determine the drug in the biological fluid. In this method, blank urine or blood sample is taken from the test animal before the experiment. The test dosage form is administered to the animal and at appropriate intervals of time the blood or urine sample are collected and assayed for the drug content. From the data ,we can determine the rate and extent of drug absortption Siddhapura Pratik ( M.Pharm Pharmaceutics)

57 Direct method In this method, the experimental animal chosen should bear some resemble to man. It is reported that pigs most closely resemble to man but are not used due to the handling problems. The other animal that can be used are dogs, rabbits and rats. Siddhapura Pratik ( M.Pharm Pharmaceutics)

58 Indirect method When the measurement of drug concentration in blood or urine is difficult or not possible , but a sensitive method is available to test the activity, then absorption studies can be done by this indirect method. In this method, pharmacological response of the drug is related to the amount of drug in the body. The response is determined after the administration of a test dosage form, LD 50 appears to be dependent on the rate of the absorption of drug. Siddhapura Pratik ( M.Pharm Pharmaceutics)

59 In situ method It stimulated the in vivo conditions for drug absorption and are based on perfusion of a segment of GIT by drug solution and determination of amount of drug diffused through it. In situ refers to those method in which the animal’s blood supply remains intact in which the rate of absorption determined from these methods may be more realistic than those determined from in vitro techniques. These models are powerful tools to study the mechanistic aspects of these important process. Acts as a bridge between in vivo and in vitro methods. Siddhapura Pratik ( M.Pharm Pharmaceutics)

60 In situ method Absorption of drug from small intestine
Siddhapura Pratik ( M.Pharm Pharmaceutics) Absorption of drug from small intestine Absorption of drug from stomach Intestinal loop techniques Doluisio method Perfusion technique Single pass perfusion method

61 Doluisio method Siddhapura Pratik ( M.Pharm Pharmaceutics)

62 Single pass perfusion method
Siddhapura Pratik ( M.Pharm Pharmaceutics)

63 Generic biologics (biosimilar drug products)
Traditional drugs are called small-molecule agents because the active ingredient is usually a single, discrete chemical entity. Biologic drugs are complex products that are derived from biologic sources (human, animal, microorganisms, or yeast). Biologics include viruses, genes, blood and body tissues, antibodies, toxins or antitoxins, vaccines, and related products used for treating disease. Until now, it has not been possible to develop generic versions of these products because of their complex manufacturing requirements and the difficulty in defining their exact composition. Siddhapura Pratik ( M.Pharm Pharmaceutics)

64 Generic biologics (biosimilar drug products)
The U.S. Food and Drug Administration (FDA) requires manufacturers to submit a proposed product for approval as a biosimilar drug or an interchangeable drug, rather than as a generic equivalent. Biosimilars are very similar to the original brand name biologic drug they are compared to. Only minor differences in clinically inactive components are allowable in biosimilar products. Interchangeable drugs, additionally, are expected to provide the same benefits and risks as the original brand name biologic. Zarxio is a biosimilar drug to filgrastim (a drug used in cancer patients to help maintain their white blood cell counts). It is the first drug approved by the FDA as a biosimilar, not as an interchangeable, product. This means that Zarxio may be prescribed by a doctor, but it cannot be substituted (interchanged) for filgrastim by a pharmacist without the approval of the prescribing doctor. Siddhapura Pratik ( M.Pharm Pharmaceutics)

65 Generic biologics (biosimilar drug products)
Ongoing scientific developments may allow the creation of generic biologic products in the next several years. The advantage of generic biologic drugs for manufacturers, pharmacies, and consumers is that they could be freely interchanged and compete against one another for inclusion on a hospital or health plan drug list. Having different brands of very similar biologic products, as with epoetin, a hormone to increase red blood cell count, does not offer all the benefits of generically equivalent products. Siddhapura Pratik ( M.Pharm Pharmaceutics)

66 Siddhapura Pratik ( M.Pharm Pharmaceutics)

67 Siddhapura Pratik ( M.Pharm Pharmaceutics)

68 Siddhapura Pratik ( M.Pharm Pharmaceutics)

69 Clinical significance of .bioequivalence studies
Clinical interpretation is important in evaluating the results of a bioequivalence study. Differences of less than 20% in AUC & Cmax between drug products are unlikely to be clinically significant in patients. A small ,statistically significant difference if the study well controlled & the number of subjects is sufficiently large. Above MEC & do not reach the MTC. Elderly or patients. Normal healthy volunteers. Minimize product to product variability by different manufactures & lot to lot variability with a single manufacture. Siddhapura Pratik ( M.Pharm Pharmaceutics)

70 Special concerns in bioavailability and bioequivalence studies
For certain drugs and dosage forms , systemic bioavailability and bioequivalence are different to ascertain for e.g. Cyclosporine, verapamil are considered to be highly variable. The number of subjects required to demonstrate bioequivalence for these drug products may be excessive , requiring more than 60 subjects. The intrasubject variability may be due to the drug itself or to the drug formulation or to both. The FDA has held public forums to determine whether the current bioequivalence guidelines need to be changed for these highly variable drugs. Siddhapura Pratik ( M.Pharm Pharmaceutics)

71 Generic substitution Generic substitution is the term applied to the substitution of a prescribed branded drug by a different form of the same active substance. The generic is usually unbranded Brand name : zovirax® ( API is acyclovir) Generic name : acyclovir However, therapeutic classes such as hormones and drugs with narrow therapeutic index (anticonvulsants, anticoagulants ,etc.) may not be appropriate for generic substitution because this drug cause serious toxicity or therapeutic failure when minor change occur in dose size during manufacturing process. Siddhapura Pratik ( M.Pharm Pharmaceutics)

72 Branded Medicine(patented drug)
Siddhapura Pratik ( M.Pharm Pharmaceutics)

73 Siddhapura Pratik ( M.Pharm Pharmaceutics)
Branded Generic Medicine (Standard company) Siddhapura Pratik ( M.Pharm Pharmaceutics)

74 Siddhapura Pratik ( M.Pharm Pharmaceutics)
Generic Medicine Siddhapura Pratik ( M.Pharm Pharmaceutics)

75 Reference Brahmankar, D. M and Jaiswal, Sunil. B (2009). Biopharmaceutics and Pharmacokinetics – A Treatise. 2 nd edition. Vallabh Prakashan, Page no and Dr. Tipnis H.P. and Dr. Bajaj Amrita, Principles and applications of Biopharmaceutics and Pharmacokinetics, 1 st edition 2002, reprint 2005, career publication, Page no  Leon shargel, Susanna wu-pong, Andrew B.C.Yu , Applied Biopharmaceutics & Pharmacokinetics, 5 th edition 2005, published by the Mc Graw hills companies, page no & Siddhapura Pratik ( M.Pharm Pharmaceutics)

76 Reference Biopharmaceutics and pharmacokinetics - Dr. Shobha Rani R.
Biopharmaceutics and pharmacokinetics - J.S Kulkarni, A.P. Pawar, V.P. Shedbalkar Web site : generic-drugs/generic-biologic-drugs biosimilars-whos-who/ Siddhapura Pratik ( M.Pharm Pharmaceutics)

77 Thank you Siddhapura Pratik ( M.Pharm Pharmaceutics)


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