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 Advance Pharmaceutical Journal 2017; 2(6): 204-209 204

Review Article
Biopharmaceutical Classification System: Tool based prediction for drug dosage
formulation
Ajay Kumar Shukla*, Ram Singh Bishnoi, Suresh Kumar Dev, Manish Kumar, Vikas Fenin
Mohanlal Sukhadia University Udaipur Rajasthan-313001 India

Received: 2 December 2017 Revised: 30 December 2017 Accepted: 24 January 2018

Abstract
The Biopharmaceutical Classification System (BCS) has been a predictive tool for assess the prospective effects of
formulation on the human, drug oral bioavailability. When used in combination with in vitro dissolution tests, the
BCS can maintain the prediction of in vivo product performance and the development. The biopharmaceutical
classification system (BCS) is a new perception in the field of pharmaceutical science. This is a helpful tool for the
formulation scientists, for the selection and design of the formulation of any drug molecules. The current
developments have also enabled us to predict the solubility and permeability character of the drug molecule in the
early development stages so that the necessary structural changes can be made to the molecule in order to optimize the
pharmacokinetic parameters. The BCS has also got a place in a variety of guidance documents of regulatory
importance. The article sheds light on the possible new criteria and class limits proposed for additional biowaivers
based on the underlying physiology of the gastrointestinal tract in mandatory cases. The prospective applications of
BCS in drug discovery, drug delivery and drug research as well as extension for BCS are discussed including the
development of new drugs and oral controlled release products.
Keywords: Biopharmaceutical classification system, drug delivery, biowaivers

Introduction solution, and finding the correct cooperate is not

The oral route of drug administration is the mainly important straightforward and simple. Hence a fast screen is needed,
method for administering drugs for systemic effects. When a to enable them to formulate intelligently. For this purpose
new drug is discovered, one of the first questions, a the drug substances are categorized into four classes based
pharmaceutical company asks is whether or not the drug can be on their solubility parameter and permeabilityto bio-
successfully administered by the oral route, for its intended membranes, and such a classification system is called as a
effect. The development of dosage forms specially for the Biopharmaceutical Classification System (BCS) (Amidon
prolonged release purpose has been a challenge to formulation et al., 1995).
scientists, because of many free factors governing the Aim of Biopharmaceutics Classification System
absorption of the drug from the gastrointestinal tract (Khan et To improve the efficiency of the drug molecules
al., 2001) and competitive objectives, that is, any action taken development and review process by recommending a
to improve one objective or set of objectives may cause another strategy for identifying expendable clinical bioequivalence
objective or set of objectives to degrade (Sachan et al., 2006). test. 2. To recommend a class of immediate-release (IR)
For example, modifying the solubility of the drug substance to solid oral dosage formulations for which bioequivalence
lengthen its release in the gastrointestinal tract may cause a may be assessed based on in vitro dissolution tests. 3. To
reduction in the overall payload of formulation. A trial and recommend methods for classification according to dosage
error method of formulation does not allow the formulator to form on the basis of dissolution along with the solubility
know how close a particular formulation is to the optimum and permeability characteristics of the drug molecules
(Amidon et al., 1995).
*Address for Corresponding Author: The Biopharmaceutics Classification System (BCS) is not
Ajay Kumar Shukla only useful tool for provide waivers for in vivo
Mohanlal Sukhadia University Udaipur-313001, Rajasthan India bioequivalence studies but also for helping in the discovery
Email: ashukla1007@gmail.com and prediction for development of new drugs formulation.
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 Advance Pharmaceutical Journal 2017; 2(6): 204-209 205

It is because BCS is based on a scientific framework elaborate principal parameter for bioavailability. These drugs reveal
the three rate limiting steps in oral absorption. The three variable bioavailability and need improvement in the
necessary vital steps for a drug to be absorbed are (1) release of dissolution rate by different methods for improvement in
drug from dosage systems, (2) maintenance of dissolved state bioavailability. These are also appropriate for controlled
throughout gastrointestinal fluid system, and (3) permeation of release development. The technologies under this class
drug molecules through GI membrane into hepatic circulation include the approaches such as classical micronization,
and. There is a fourth step, i.e. enterohepatic metabolism that stabilization of high-energy states (including lyophilized
increases the systemic availability as well as release of fast-melt systems), use of surfactants, emulsion or
metabolites into the systemic circulation. microemulsion systems, solid dispersion and use of
Within the framework of human pharmaceuticals, drugs complexing agent such as cyclodextrins. The technologies
molecules can be classified into one of the following four under this class include: Soft Gel (soft gelatin capsule
Biopharmaceutical Classification Systems are categories as: formulation), Zer-Os tablet technology (osmotic system),
Triglas and nanosized carriers such as nanoemulsion,
Class I: high solubility, high permeability: generally very well-
nanosuspension and nanocrystals are treated as hopeful
absorbed molecules
means of increasing solubility and BA of poorly water-
Class II: low solubility, high permeability: exhibit dissolution soluble active ingredients.
rate-limited absorption
Class III: Drugs molecules of this class permeation through
Class III: high solubility, low permeability: exhibit the intestinal membrane form the rate-determining step for
permeability-limited absorption these drugs molecules. Since absorption is permeation rate
Class IV: low solubility, low permeability: extremely poor oral limited, bioavailability is self-governing of drug release
bioavailability from the dosage form. For example, the different ranitidine
products having dissimilar dissolution profiles produce
Characteristics of the drugs under BCS (Lobenberg et al., 2000)
super imposable plasma concentration versus time profile
Class I: In-vivo these drugs behave like an oral solution has fast in-vivo. These drugs usually show low bioavailability and
dissolution and fast bioavailability. Since the dissolution and permeability enhancement is normally required. These
absorption of class I drugs is extremely fast, bioavailability and drugs are challenging for controlled release development.
bioequivalence are pointless for the products of such drugs.
Class IV: Drugs molecules of this class show poor and
These drugs are good candidates for controlled drug delivery if
unpredictable bioavailability. The generally bioavailability
they be eligible pharmacokinetic ally and pharmacodynamically
is governed by numerous factors such as rate of dissolution,
for the point. Gastric emptying is often the rate governing
intestinal permeability, gastric emptying, and so on. These
limitation in this case. The Class I drugs molecules are not those
drugs are usually not suitable for oral drug delivery or else
in which either solubility or permeability is limiting within the
some special drug delivery technologies such as nano-
target regions of the GI tract. The drug molecules release in such
suspensions will be desirable.
cases can be modulated using controlled release technology.
Controlled release technologies for Class I drugs molecules Perception behind BCS
includes number of products like as Multiporous oral drug The in-vivo presentation of orally administered drugs
absorption system, Single composition osmotic tablet system, depends ahead their solubility and tissue permeability
Microsphere, constant surface area drug delivery shuttle, character. The release rate or solubility of the drug
Diffusion controlled matrix system, Delayed pulsatile hydrogel molecules will not be a governing limit, if the absorption of
system, Dual release drug absorption system), Granulated the drug is permeation rate limited and in such cases the in-
modulating hydrogel system, Intestinal protective drug vitro dissolution study can be used to express the
absorption system, Microparticle Drug Delivery Technology, bioavailability (BA) or bioequivalence (BE) of the drug
Pelletized pulsatile delivery system, Bioerodible enhanced oral molecules through in vitro-in vivo correlation (IVIVC). On
drug absorption system, Programmable oral drug absorption the other side, if absorption of the drug molecules is
system, Spheroidal oral drug absorption system, Solubility dissolution rate limited that way the drug in the
modulating hydrogel system and Stabilized pellet delivery gastrointestinal fluid passes freely throughout the bio-
system. membranes at a rate higher than it dissolves or is released
Class II: Drugs molecules belong contains low solubility and from the dosage formulation. The specifically planned in-
high permeability, therefore, the dissolution rate becomes the vivo study will be mandatory in such a case, to access the

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 Advance Pharmaceutical Journal 2017; 2(6): 204-209 206

absorption rate, and therefore its bioavailability and to reveal the Bioequivalence: define as the active moiety in
bioequivalence finally. Such a drug molecules is good candidates pharmaceutical equivalents or pharmaceutical
for controlled delivery provides if they qualify in terms of their alternatives becomes available at the site of drug action
pharmacokinetics and pharmacodynamics for controlled release when administered at the same molar dose under similar
development. Besides if drug molecules having low solubility environment in an appropriately designed study.
and a slow dissolution rate, the release will routinely get slower The Biopharmaceutical Drug Disposition Classification
and the dosage form need not have an inbuilt release retardation System (BDDCS)
mechanism, fairly the absorption will now be governed by the
The evaluations of following four steps are uses for oral
gastric emptying rate. Therefore, the dosage form must be able to
absorption and, efficacious drugs. as determination of
restrain within the absorption window for a sufficient time so that
solubility, permeability, and metabolic stability. These oral
absorption can take place. In such case, a hydrodynamic ally
absorption screening tests are often referred as
balanced (floating) system or a mucoadhesive dosage
pharmaceutical profiling. The pharmaceutical researcher in
formulation will provide the purpose. Consequently the BCS can
earlier development of the formulation of dosage forms
work as a guide tool for the improvement of various oral drug
mostly utilizes pharmaceutical profiling data to establish
delivery technologies (Johnson et al., 2006).
the preliminary BCS classification for the lead compound.
It allows for the prediction of In-vivo pharmacokinetics of oral Because BCS has ramification in drug approval process
immediate-release (IR) drug molecules by classifying drug from FDA and other regulatory agencies, during the
compounds into four classes based on their solubility related to discovery of new drugs molecules, classification of a
dose and intestinal permeability in combination with the compound to BCS 2, BCS 3 or BCS 4 communicates to
dissolution properties of the dosage form. Biopharmaceutical Discovery the need to enhance solubility and/or
Classification System (BCS) guidance was provided by US Food permeability for following compounds. In the same vein, a
and Drug Administration (FDA), to improve the efficiency of BCS classification other than 1 communicates to
drug product development process. The Biopharmaceutical Manufacturing that may lead to higher formulation risks
Classification System (BCS) is a system to differentiate the drugs during drug development. Most importantly, it warns the
on the basis of their solubility and permeability. It is a guide for clinician of the potential for a large unpredictability in
predicting the intestinal drug molecules absorption according to exposure and a significant food effect.
Food and Drug Administration. BCS is based on scientific
The BCS is a vital tool that facilitates product improvement
framework relating three rate limiting steps in oral absorption.
and regulatory decisions. By understanding the solubility of
The three essential steps for a drug to be absorbed are: (1) Release
molecules in biorelevant media and its permeability across
of drug molecules, from dosage forms; (2) Maintenance of
biological membranes, the rate limiting factors determining
dissolved state throughout Gastro-intestinal (G.I) tract; (3)
the rate and extent of oral drug molecules absorption can be
Permeation through G.I. membrane into hepatic circulation.
identified. This information can be invaluable for
Solubility of drug classification is according to the United States predicting the possible influence of formulation and
Pharmacopoeia (USP) aperture 2. The intestinal permeability physiological variables on oral drug bioavailability.
classification is based on a assessment to the intravenous
The drugs molecules are classified in BCS on the basis of
injection. All these factors are very important, since 85% of the
following parameters:
most sold drugs in the USA and Europe are orally administered.
Until now, application of BCS has been moderately hindered by (1) Solubility, (2) Permeability and (3) Dissolution
the lack of a freely available and accurate database summarizing The class boundaries for the parameters are:
solubility and permeability characteristics of drug molecules.
Solubility determination
Consequently the facts of BCS help the formulation scientist to
develop a dosage form based on mechanistic rather than The solubility of any drug material can be distinct as the
empirical approaches (FDA Guidelines, 2000). amount of material that has passed into solution when
equilibrium is attained between the solution and excess
Important term under BCS
(undissolved substance) at a given temperature and
Bioavailability: define as the rate and extent to which the pressure (Lobenberg et al., 2000). A drug material or an
active ingredient or active moiety is absorbed from a drug active pharmaceutical ingredient (API) is considered highly
molecule of product and becomes existing at the site of soluble when the highest dose strength is soluble in 250 ml
action. or less of aqueous medium over a specific pH range

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 Advance Pharmaceutical Journal 2017; 2(6): 204-209 207

(Johnson et al., 2006). The pH solubility profile of the drug dissolving when no less than 85 % of the labeled amount of
material is determined at 37 6 18C in aqueous medium with pH in the drug molecules dissolves within 15 minutes using USP
the range of 1-7.5 as per United States Food and Drug Dissolution Apparatus- I at 100 RPM or Apparatus - II at 50
Administration (USFDA) guidelines, 1.2-6.8 as per World RPM in a volume of 900 ml or less in the following media:
Health Organization (WHO) guidelines (Gothoskar et al., 2005) 0.1 N HCl or simulated gastric fluid or pH 4.5 buffer and pH
and 1-8 as per European Medicines Academy (EMEA). A 6.8 buffer or simulated intestinal fluid. According to
sufficient number of pH conditions must be evaluated to USFDA BCS guidance (Martinez et al., 2002) an IR drug
accurately. The number of pH conditions for a solubility product is considered rapidly dissolving when no less than
determination depends upon ionization characteristics of the test 85% of the labeled amount of the drug substance dissolves
drug material. A minimum of three replicate determinations of within 30 minutes, using USP apparatus I at 100 rpm (or
solubility in each pH condition should be carried out to expect Apparatus II at 50 rpm) in a volume of 900 ml or less in each
accurate solubility. Standard buffer solutions described in medium: 0.1 N HCl or simulated gastric fluid USP without
pharmacopoeias are considered appropriate for use in solubility enzymes; buffer (pH 4.5); and buffer (pH 6.8) or simulated
studies. Other than shake-flask method, can also be used with intestinal fluid USP without enzymes. According to WHO
validation to support the ability of such methods to predict BCS guidance a multisource product (pharmaceutically
equilibrium solubility of test drug substance. If degradation of equivalent or pharmaceutically alternative products that
drug is observed as a function of buffer composition and/or pH, it may or may not be therapeutically equivalent) is considered
should be taken into consideration. The concentration of drug to be very rapidly dissolving when no less than 85% of the
molecules in selected buffers or pH conditions should be labeled amount of the drug substance dissolves in 15
determined with a validated solubility indicating assay method minutes using a paddle apparatus at 75 rpm or a basket
that can distinguish between the drug substances from its apparatus at 100 rpm in a volume of 900 ml or less in each
degradation products (Martinez et al., 2012). medium: HCl solution (pH 1.2); acetate buffer (pH 4.5); and
Permeability phosphate buffer (pH 6.8). A multisource product is
considered to be quickly dissolving when no less than 85%
The permeability class boundary is based indirectly on the extent
of the labeled amount of the drug substance dissolves in 30
of absorption of a drug molecules in humans and directly on
minutes using a paddle apparatus at 75 rpm or a basket
measurements of the rate of mass transmit across human
apparatus at 100 rpm in a volume of 900 ml or less in each of
intestinal membrane. Otherwise, nonhuman systems able of
the media: HCl solution (pH 1.2); acetate buffer (pH 4.5);
predicting the amount of drug molecules absorption in humans
and phosphate buffer (pH 6.8). According to EMEA BCS
can be used (e.g., in vitro epithelial cell culture methods). In mass
guidance drug products are considered very rapidly
balance studies, unlabeled, stable isotopes or radio labeled drug
dissolving when more than 85% of the labeled amount is
molecules are used to find out the extent of drug absorption. In
dissolved in 15 minutes, using USP Apparatus I at 100 rpm
absolute bioavailability studies, oral bioavailability is
(or Apparatus II at 50 rpm) in a volume of 500 ml in each of
determined and compared against the intravenous bioavailability
the media: 0.1 N HCl or simulated gastric fluid without
as reference. Intestinal perfusion models and in vitro methods are
enzymes; buffer (pH 4.5); and buffer (pH 6.8) or simulated
recommended for passively transported drugs (Rubas W et al.,
intestinal fluid without enzymes and similarity of
1993). An interesting option to intestinal tissue models is the use
dissolution profiles should be demonstrated. Lipophilic
of in vitro systems based on the human adenocarcinoma cell line
drugs may be very poorly soluble in water and in simple
Caco-2. These cells provide as a model of small intestinal tissue.
buffers, but in the GI fluids the bile to a significant extent
The differentiated cells reveal the microvilli typical of the small
can often solubilize them. Increases in solubility of one to
intestinal mucosa and the integral membrane proteins of the
two orders of magnitude are possible for compounds with
brush-border enzymes. They also form the fluid-filled domes
log P values of .4. For promising compounds that are both
typical of a permeable epithelium. Recent investigations of
ionizable and lipophilic, extensive solubility experiments
Caco-2 cell lines have indicated their ability to transport ions,
in biorelevant media will help to characterize the likely
sugars and peptides. These properties have established the Caco-
solubility behavior in vivo. Another approach is to use
2 cell line as a reliable in vitro model of the small intestine (Davis
aspirates from human volunteers, although volumes
et al., 2006).
aspirated typically are small and the choice of experiments
Dissolution and apparatus therefore is also limited. Next issue is the use
Immediate release drugs formulation is considered rapidly of 250 m (Chiou et al., 2000).

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 Advance Pharmaceutical Journal 2017; 2(6): 204-209 208

Biowaivers (BDDCS) has been used to forecast the drug disposition and
The term biowaiver is very useful in the regulatory drug approval potential drug-drug interactions in the intestine and the liver
process when the dossier (application) is approved based on and potentially the kidney and brain. While the solubility
evidence of equivalence other than through in vivo equivalence criteria for the BCS and BDDCS are the similar. For the
testing. Biowaiver means to achiev waive off for carrying out BDDCS, the second classification is linked to the reporting
expensive and time-consuming BA and BE studies. A biowaiver of drug metabolism. The assessment of permeability in the
has been regarded as an official approval of the waiver for BCS is linked to the reporting of intestinal absorption, i.e., a
conducting a bioequivalence study in the context of an drug molecules is considered to be highly permeable when
application for drug molecules approval process. The BCS- the extent of the systemic absorption (parent drug plus
based biowaivers related to pre- (IND/NDA and ANDA), post metabolites) in humans is determined to be at least 90% of
approval phases. BCS-based biowaivers are relevant for an administered dose based on a mass balance
immediate-release solid oral drug formulations containing one or determination or in comparison to an intravenous reference
more of the API(s) mentioned above if the required data ensure dose (Martinez et al., 2002). Accordingly, the BCS and
the similarity of the submitted pharmaceutical product and the BDDCS classification of a drug may differ. Once the
proper pharmaceutically equivalent comparator product. BCS- solubility and permeability characteristics of a drug are
based biowaiver has become an important and cost-saving tool in known, the formulation scientist can then, based on BCS,
approval of basic (generic) drugs (FDA Guidance 2000). easily decide which drug delivery technology will best and
Presently BCS class I drugs and some class III drugs are suitable help in getting the optimum pharmacokinetic
for biowaivers. The drug molecules should be highly soluble and characteristics. The major task in the development of drug
highly permeable. An IR drug product should be quickly delivery systems for class I drug is to achieve a targeted
dissolving. The drug molecules should not be a narrow release profile associated with the particular
therapeutic index drug. Excipients used in the dosage pharmacokinetic and pharmacodynamic properties.
formulation should have been used earlier in FDA approved IR Formulation approaches include both the control of release
solid dosage forms. Used for waivers of an in vivo relative rate and physiochemical properties of drugs like the pH-
bioavailability study, dissolution should be greater than 85% in solubility profile of the drug. The systems that are
30 min in the three recommended dissolution media (acidic developed for class II drugs are based on the micronization,
media, such as 0.1 N HCl or Simulated Gastric Fluid USP lyophilization, addition of surfactants, and formulation as
without enzymes, a pH 4.5 buffer; and a pH 6.8 buffer or emulsions and microemulsion systems, use of complexing
Simulated Intestinal Fluid USP without enzymes). Used for agents like cyclodextrins, and so on. Class III drugs are
waivers of in vivo bioequivalence, test and reference products required for technologies that address the fundamental
should exhibit similar dissolution profiles under the dissolution limitations of absolute or regional permeability. Peptides
test conditions defined for rapidly dissolving products (Amidon and proteins constitute, solely, the class III drugs; these are
et al., 1995). now the center of focus for research in drug delivery. The
Exceptions BCS-based biowaivers are not applicable for the class IV drugs present a major challenge for the
subsequent: Narrow therapeutic range drug molecules products development of drug delivery systems and the route of
as those containing certain drug molecules that are subject to choice, due to their poor solubility and permeability
therapeutic drug concentration or pharmacodynamic characteristics. These are often administered by parenteral
monitoring, and/or where product labelling indicates a narrow route with the formulation containing solubility enhancers
therapeutic range designation. Examples like digoxin, lithium, (Takagi et al., 2006).
phenytoin, theophylline, and warfarin. Because not all drugs Conclusion
molecules subject to therapeutic drug concentration or
The BCS is the tool for the prediction of in vivo
pharmacodynamic monitoring are narrow therapeutic range
performance of the drug molecules, and development of
drugs. Drug products designed to be absorbed in the Oral Cavity:
drug delivery system to suit that performance. BCS
A applies for for a waiver of in-vivo BA/BE studies based on the
principles offer a reasonable process for testing and
BCS is not appropriate for dosage forms for absorption through
approving drug molecules product quality. BCS
the oral cavity (e.g., sublingual or buccal tablets) (Amidon et al.,
applications used for Class 2 and 3 are challenging, but at
1995).
the same time provides opportunities for lowering
Application of BCS in drug delivery technology regulatory burden with scientific rational. BCS also
Biopharmaceutical Drug Disposition Classification System provides an possibility to predict drug disposition,

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Advance Pharmaceutical Journal 2017; 2(6): 204-209 209

transport, absorption, elimination. Martinez MN, Papich MG. 2012. Drug solubility
Conflict of interest classification in the dog. Journal of Veterinary
Pharmacology and Therapeutics, 35(Suppl. 1):87–91.
Authors do not declare any conflict of interest.
Mirja, T, Gray VA. 2004. Meeting report: Conference on
References
Dissolution, Bioequivalence and Bioavailability.
Amidon GL, Lennerlas H, Shah VP, Crison JR. 1995. A Dissolution Technology, 11:25-8.
theoretical basis for a biopharmaceutic drug classification:
Rubas W, Jezyk N, Grass GM. 1993. Comparison of the
The correlation of in vitro drug product dissolution and in
permeability characteristics of a human colonic
vivo bioavailability. Pharmaceutical Research, 12:413-20
epithelial (Caco-2) cell line to colon of rabbit, monkey,
Chiou WL, Jeong HY, Chung SM, Wu TC. 2000. Evaluation of and dog intestine and human drug absorption.
using dog as an animal model to study the fraction of oral dose Pharmaceutical Research, 10:113–8.
absorbed for 43 drugs in humans. Pharmaceutical Research,
Sachan NK, Singh D. 2006. Evaluation of dried pulp from
17:135–40.
Carica papaya fruits as disintegrating agents in the
Davis JL, Little D, Blikslager AT, Papich MG. 2006. Mucosal formulation of metformin hydrochloride dispersible
permeability of water-soluble drugs in the equine jejunum: a tablets. Journal of Assam Science Society; 46:20-2.
preliminary investigation. Journal of Veterinary
Takagi T, Ramachandran C, Bermejo M, Yamashita S, Yu
Pharmacology and Therapeutics, 29(5):379–85.
LX, Amidon GL. 2006. A provisional
FDA 2000. Guidance for Industry, CDER, “Waiver of in vivo biopharmaceutical classification of the top 200 oral drug
bioavailability and bioequivalence studies for immediate- products in the United States, Great Britain, Spain, and
release solid oral dosage forms based on a biopharmaceutics Japan. Molecular Pharmaceutics, 3(6):631–43.
classification system.
Verma RK, Garg S. 2001. Current status of drug delivery
Food and Drug Administration 2000. Guidance for industry, technologies and future directions. Pharmaceutical
waiver of in vivo bioavailability and bioequivalence studies Technology (online), 25(2):1-14.
for immediate-release solid oral dosage forms based on a
World Health Organization. 2006. Proposal to waive in vivo
biopharmaceutics classification system, Food and Drug
bioequivalence requirements for WHO model list of
A d m i n i s t r a t i o n , R o c k v i l l e , M D , Av a i l a b l e a t
essential medicines immediate-release, solid oral
http://www.fda.gov/cder/guidance/index.htm
dosage forms. World Health Organization, Technical
Gothoskar AV. 2005. Biopharmaceutical classification system of Report Series No. 937.
drugs [online]. Pharmaceut Rev. Available from: URL: http://
www. pharmainfo.net/ reviews/biopharmaceutical-
classification-drugs.
Johnson SR, 2006. Zheng Weifan. Recent progress in
computational prediction of aqueous solubility and
absorption. AAPS Journal, 8:E27-40.
Khan GM. 2001. Controlled release oral dosage forms: Some
recent advances in matrix type drug delivery systems. The
Science; 1:350-54.
Lobenberg R, Amidon GL. 2000. Modern bioavailability,
bioequivalence and biopharmaceutics classification system.
New scientific approaches to international regulatory
standards. European Journal of Pharmaceutics and
Biopharmaceutics, 50:3-12
Martinez MN, Amidon GL. 2002. A mechanistic approach to
understanding the factors affecting drug absorption: a review
of fundamentals. Journal of Clinical Pharmacology,
42(6):620–43.

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