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    The BCS is a scientific framework for classifying a drug substance based on its aqueous

    solubility and intestinal permeability. When combined with the in  vitro dissolution

    characteristics of the drug product, the BCS takes into account three major factors solubility,

    intestinal permeability, and dissolution rate, all of which go!ern the rate and e"tent of oral

    drug absorption from #$ solid oral%dosage forms.

    &ccording to the BCS the drugs can be categori'ed in to four basic groups on the bases of their solubility and permeability (#T mucosa. (Table 1)

    The solubility classification of a drug in the BCS is based on the highest dose strength in an

    #$ product. & drug substance is considered highly soluble when the highest strength is

    soluble in )*+ m or less of aqueous media o!er the p- range of .+/0.*1 otherwise, the drug

    substance is considered poorly soluble. The !olume estimate of )*+ m is deri!ed from

    typical bioequi!alence study protocols that prescribe the administration of a drug product to

    fasting human !olunteers with a glass 2about 3 ounces4 of water.







    Class I -igh 5-igh (astric emptying

    #6#6C e"pected if 

    dissolution rate is

    slower than gastric

    emptying rate.

    7therwise limited or 

    no correlation.

    Class II -igh 5ow 8issolution

    #6#6C e"pected if in%!itro dissolution

    rate is similar to in%

    !i!o dissolution rate,

    unless dose is !ery


    Class III ow 5-igh 9ermeability

    &bsorption is rate

    determining and

    imited or no #6#6C

    with dissolution.

    Class IV ow 5ow Case by caseimited or no #6#6C


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      (Table 1)

    IVIVC expe!a!"#$s %#& IR p'!s base' #$ !e BCS Class

    The permeability classification is based directly on the e"tent of intestinal absorption of a

    drug substance in humans or indirectly on the measurements of the rate of mass transfer 

    across the human intestinal membrane. & drug substance is considered highly permeable

    when the e"tent of intestinal absorption is determined to be :+; or higher. 7therwise, thedrug substance is considered to be poorly permeable.

    &n #$ drug product is characteri'ed as a rapid dissolution product when not less than 3*; of 

    the labelled amount of the drug substance dissol!es within

    -Cl or =S9 simulated gastric fluid without en'ymes1

    )4 & p- ?.* buffer1 and

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    • To impro!e the efficiency of drug de!elopment and the re!iew process by

    recommending a strategy for identifying e"pendable clinical bioequi!alence tests• To recommend a class of immediate%release

    2#$4 solid oral dosage forms for which bioequi!alence may be assessed based on in

    !itro dissolution tests.

    • To recommend methods for classification according to dosage form dissolution, along

    with the solubility and permeability characteristics of the drug substance.

    The classification is associated with drug dissolution and absorption model, which identifies

    the key parameters controlling drug absorption as a set of dimensionless numbers G

    • Te Abs#&p!"#$ N+be& (A$) is the ratio of the Hean $esidence Time 2Tres4 to the

    Hean &bsorption Time 2Tabs4 and it could be estimated using equation.

    A$ , (T&es / T abs) , (-.1R0L/) (R/Pe%%) 22 . (0)

    • Te D"ss#l!"#$ $+be& is a ratio of mean residence time to mean dissolution time.

    #t could be estimated using equation ).

    D$ ,(T&es/T'"ss),(-.1 R0L/) / (3 &0 /- D Cs +"$)...(-)

    • Te D#se $+be& is the mass di!ided by an uptake !olume of )*+ ml and the drugssolubility. #t could be estimated using equation ).

    D4 , D#se/(V4 xC +"$s) 22222222222()

    • Te +ea$ &es"'e$e !"+e here is the a!erage of the residence time in the stomach,

    small intestine and the colon.


    D tube length,$ D tube radius,

    I D

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    Csmin is minimum aqueous solubility in the physiological p- range of %3


    Class I '&5s e"hibit a high absorption number and a high dissolution number. The ratelimiting step is drug dissolution and if dissolution is !ery rapid then gastric emptying rate

     becomes the rate determining step. Bioa!ailability and dissolution is !ery rapid. So

     bioa!ailability and bio%equi!alency studies are un necessary for such product. #6#6C can not

     be e"pected. Thes compounds are highly suitable for design the S$ and C$ formulations.

    F"amples include Letoprofen, >apro"en, Carbama'epine, 9ropanolol, Hetoprolol,

    8iltia'em, 6erapamil etc.

    Class II '&5s ha!e a high absorption number but a low dissolution number. #n !i!o drug

    dissolution is then a rate limiting step for absorption e"cept at a !ery high dose number.

    These drug e"hibited !ariable bioa!ailability and need the enhancement in dissolution for 

    increasing the bioa!ailability. Thes compounds are suitable for design the S$ and C$ formulations. #n !itro% #n !i!o correlation 2#6#6C4 is usually e"pected for class ## drugs.

    F"amples include 9henytoin, 8ana'ol, Letocona'ole, Hefenamic acid, >ifedinpine,

    Aelodipine, >icardipine, >isoldipine etc.


    ! =se of surfacrtants

    ! Comple"ation

    ! By making the produg

    ! =se of selected polymeric forms

    ! =se of sol!ates and hydrates

    ! =se of salt of weak acids and weak bases

    ! Buffeirng the p- of the microen!ironment



    ! Hicroni'ation 2reduced the particle si'e to increase the surface4

    ! Sol!ent deposition 2deposition of poorly soluble drugs on inert material4! Solid despertions 2dispersion of poorly soluble drugs in a solid matri" of the water soluble


    ! =se of the surfactants2to increasing the surface area by facilitating proper wetting4

    F#& Class III '&5s  permeability is rate limiting step for drug absorption. These drugs

    e"hibit a high !ariation in the rate and e"tent of drug absorption.

    Since the dissolution is rapid, the !ariation is attributable to alteration of physiology and

    membrane permeability rather than the dosage form factors.

    These drugs are problematic for controlled release de!elopment. These drugs showed the low bioa!ailability and need enhancement in permeability.

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    F"amples include &cyclo!ir, &lendronate, Captopril, Fnalaprilat >eomycin B etc.

    Aollowing permeation enhancers can be used

    ! S6$!e!"s s&%a!a$!s eg. SS,polysorbate )+ M 3+,sorbitan laurate,glyceryl monolaurate

    ! B"le Sal!s7 Sodium deo"ycholate, Sodium glycocholate, Sodium fusidate etc.! Fa!!6 a"'s a$' 'e&"8a!"8es7 7leic acid, Caprylic acid, auric acid etc.

    ! Cela!#&s9 eg Sod F8T&, Citric acid, Salicylates etc.

    ! I$ls"#$ #+plexes7 Cyclode"trins and deri!ati!es etc.

    ! M#a'es"8e p#l6+e&s7 Chitosan, 9olycarbophil etc.

    Class IV '&5s e"hibit poor and !ariable bioa!ailability. Se!eral factors such as dissolution

    rate, permeability and gastric emptying form the rate limiting steps for the drug absorption.

    These are unsuitable for controlled release. F"amples include  Chlothai'ude, Aurosemide,Tobramycine, Cefuro"ime etc.


    $elease of the drug substances from its dosage form or drug permeation through the intestinal

    membrane are the rate limiting steps for the absorption and bioa!ailability. #f the permeation

    through intestinal membrane is rate limiting, the dissolution properties may be negligible

    importance. Since the dissolution of the class # drug is !ery fast so the B&5BF studies for this

    class seem to be unnecessary. The class ### drug product are seem to be the better for B&5BF

    studies as their bioa!ailability depend on the permeability properties. 2Table 1)


    Me'"a %#& Class I sbs!a$es

    Substances that belong to class # possess good aqueous solubility and are transported through

    the (# mucosa.

    Their bioa!ailability after oral administration is usually close to ++ ;, pro!ided they are not

    decomposed in (#T and do not under go e"tensi!e first pass metabolism G0N. &fter 

    administration, the dosage form quickly passes into stomach and, usually disintegrates there,

    so it is logical to use a dissolution medium that reflects the gastric conditions. Simulated

    gastrointestinal fluid 2S(A4 without en'ymes is suitable for many immediate release dosage

    forms of this class. Aor some capsules, an en'yme 2pepsin4 may ha!e to be added to the

    medium to ensure the timely dissolution of the shell. #n case of weak acidic drugs simulated

    intestinal fluid with out en'yme may be used due to hampered dissolution of this drug by the

    S(A medium. Water is less suitable medium than the aforementioned buffers, because it has a

    nominal buffer capacity 'ero1 therefore, the p- may !ary during the test. Fnsure and Hilk as

    dissolution media can impro!e the drug solubility includes the solubili'ation of drugs in the

    fatty part of the fluid. 7f these media contains similar ratio of protein5 fat5 carbohydrate. =es

    of ensure and milk ha!e been !igorously suggested as a media suitable for simulating fedstate in the stomach.

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    Aor e"ample enteric coated dosage forms. =S9 apparatus #6 is particularly suitable for F$ 

    dosage forms (Table 0)



    1Solid 7ral 8osage Aorms


    Basket. 9addle, $eciprocating Cylinder 7r Alow Through Cell

    0 7ral Suspensions 9addle

    - 7rally 8isintegrating Tablets9addle

    Chewable Tablets Basket. 9addle, $eciprocating Cylinder With (lass Beads

    : Transdermal%9atches9addle 7!er 8isk 

    ; Topical SemisolidsAran' 8iffusion Cell

    < SuppositoriesHodified Basket. 9addle, 8ual Chamber Alow Through Cell

    = Chewable (umSpecial &pparatus 29heur4

    > 9owders &nd (ranules Alow Through Cell 29owders5 (ranules Sample Cell4

    14Hicro 9articulate

    AormulationsHodified Alow Through Cell

    11 #mplants Hodified Alow Through Cell

    (Table 0)


    &n appropriate rotational speed must be selected. #f rotation speed is !ery too low, coining

    may occur, leading to artifactually low rates of dissolution. #f the rate of rotation is too fast,

    the test will not be able to discriminate between acceptable and not acceptable batches.

    $otation speed in range *+%0* rpm appear to be suitable in case of paddle method.

    8issolution of the class first compound is relati!ely intensi!e to !ariation in this speed range

    and e!en for class ## compounds the effect is minimal. #f the basket method is used a

    rotational speed 0*%++ rpm may be suitable.


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    The duration of dissolution test must be tailored to not only the site of absorption for the drug

     but also timing of administration. #f this is best absorbed from the upper small intestine and is

    to be administered in the fasted state, dissolution test in a medium simulating fasted gastric

    conditions with duration of * to

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    The following methods can be used to determine the permeability of a drug substance from

    the gastrointestinal tractQ In vivo intestinal perfusions studies in humans.

    Q In vivo or in situ intestinal perfusion studies in animals.

    Q In vitro permeation e"periments with e"cised human or animal intestinal tissue.

    Q In vitro permeation e"periments across epithelial cell monolayer 

    To demonstrate suitability of a permeability method intended for application of the BCS, a

    rank%order relationship between test permeability !alues and the e"tent of drug absorption

    data in human subjects should be established. Aor demonstration of suitability of a method,

    model drugs should represent a range of low 2e.g., R *+;4, moderate 2e.g., *+ % 3:;4, and

    high 2 :+;4 absorption.

    C. De!e&+"$"$5 D&5 P'! D"ss#l!"#$ Ca&a!e&"s!"s

    8issolution testing should be carried out in =S9 &pparatus # at ++ rpm or &pparatus ## at *+

    rpm using :++ ml of the following dissolution media

    24 +. > -Cl or Simulated (astric Aluid =S9 without en'ymes1

    2)4 a p- ?.* buffer1 and 2

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    1. BCS "$ !e '&5 'e8el#p+e$!

    #n early drug de!elopment, knowledge of the class of a particular drug is an important factor 

    influencing the decision to continue or stops it de!elopment.

    BCS classification can be utili'ed in drug candidate selection at an early phase in drug

    de!elopment, during formulation de!elopment, and in regulatory applications.

    The BCS class of a drug indicates the rate%limiting step for oral absorption gastric emptying,

    dissolution or intestinal permeability. #n the early de!elopment phase, the permeability and

    solubility boundaries can be set as selection criteria for new drug candidates.  In vitro methods

    are utili'ed to measure solubility and permeability. Solubility is typically measured by the

    shake%flask method and permeability by Caco%) cells.

    (astric emptying of the dissol!ed drug is the rate limiting step for oral absorption of class #

    drugs with rapid dissolution. Class # drugs ha!e fa!ourable absorption properties, leading to

    rapid and complete absorption. 8rug absorption can be mediated either by passi!e

    transcellular diffusion or by acti!e transport. F!en simple, con!entional #$ formulation

    assures rapid and complete absorption for this class of drugs.

    Therefore, formulation de!elopment is fast and cheap unless other issues, such as stability or 

     production problems e"ist. #6#6Cs cannot be found for #$ formulations of class # drugs if 

    dissolution is faster than gastric emptying. Thus, the dissolution method can be a simple and

    cheap quality control tool.

    -owe!er, if a BCS biowai!er is utili'ed in a regulatory application, dissolution should be

    tested in three different media representing the p- range of the gastrointestinal tract.

    8issolution controls absorption of class ## drugs and a point%to%point relationship, i.e., le!el &

    #6#6C, can be found between in vitro dissolution and in vivo dissolution or absorption. ike

    BCS # drugs, class ## drugs ha!e high permeability, and transport may be acti!e or occur by

     passi!e transcellular diffusion.

    #f absorption is limited by solubility or dissolution, it may be incomplete. Aormulation

    de!elopment may be more challenging than for BCS # drugs if special techniques and skills

    are utili'ed to enhance drug solubility or dissolution. Aor e"ample, nanoparticles,

    microemulsion, cyclode"trins or lipid formulations can be used.

     In vitro dissolution method de!elopment also requires more time and a high le!el of 

    knowledge if in vitro conditions are to mimic drug release and dissolution in vivo. Se!eral p-

    !alues, agitation speeds, and different apparatuses should be tested. &n appropriate methodshould discriminate critical formulation or manufacturing !ariables of the product affecting

    drug dissolution in vivo. #f successful, a le!el & #6#6C may be pro!en and in vitro

    dissolution tests can be used as surrogates for in vivo  bioa!ailability and bioequi!alence


    BCS ### drugs ha!e permeability limited absorption.

    #ncomplete absorption due to limited permeability can rarely be sol!ed by formulation

    factors, because specific and non%to"ic permeability enhancers are difficult to de!elop G)3N.

    #nstead, bioa!ailability may be increased by prodrug deri!ati'ation of the parent compound,

    impro!ing drug distribution to the target tissue.

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    Those publications critici'e the current biowai!er guidelines, which are based on equilibrium

    solubility and dissolution tests, and in which the dynamic nature of drug absorption is not

    taken into account. &cidic BCS ## drugs ha!e low solubility only in the stomach, while

    solubility in the small intestine is high and the fraction of the dose absorbed can be U +.:. The

    e"tent of oral drug absorption 2i.e. &=C4 may not be sensiti!e to minor dissolution rate

    differences under the alkaline conditions in the small intestine. #n contrast, the rate of oralabsorption 2i.e. Cma"4 may be sensiti!e to differences in the dissolution rates, as was pointed

    out in simulation studies. Solubility and dissolution of acidic BCS ## drugs are site dependent,

    i.e., solubility is low in the acidic stomach and high in the alkaline small intestine. &s

    discussed pre!iously, gastric emptying of solid drugs is a highly !ariable process, since

    house%keeping wa!es occur e!ery .

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    1. Na& Te&ape!" Ra$5e D&5s

    This guidance defines narrow therapeutic range drug products as those containing certain

    drug substances that are subject to therapeutic drug concentration or pharmacodynamic

    monitoring, and 5or where product labeling indicates a narrow therapeutic range designation.

    F"amples include digo"in, lithium, phenytoin, theophylline, and warfarin.

    Because not all drugs subject to therapeutic drug concentration or pharmacodynamicmonitoring are narrow therapeutic range drugs, sponsors should contact the appropriate

    re!iew di!ision to determine whether a drug should be considered to ha!e a narrow

    therapeutic range.

    0. P'!s Des"5$e' !# be abs#&be' "$ !e O&al Ca8"!6

    & request for a wai!er of in !i!o B&5BF studies based on the BCS is not appropriate for 

    dosage forms intended for absorption in the oral ca!ity 2e.g. sublingual or buccal tablets4.


    BCS principles pro!ide a reasonable approach for testing and appro!ing drug product quality.BCS applications for Class ) and < are challenging, but at the same time pro!ides

    opportunities for lowering regulatory burden with scientific rational. BCS also pro!ides an

    a!enue to predict drug disposition, transport, absorption, elimination. The BCS is the guiding

    tool for the prediction of in vivo performance of the drug substance and de!elopment of drug

    deli!ery system to suit that performance.

    The Biopharmaceutics Classification System 2BCS4 is the result of continuous efforts in

    mathematical analysis for the elucidation of the kinetics and dynamics of the drug process in

    the gastrointestinal tract 2(#T4 for >8& 2>ew 8rug &pplication4 and &>8& 2&bbre!iated

     >ew 8rug &pplication4 filings and bio%wai!ers. This step reduces timelines in the new drug

    de!elopment process, both directly and indirectly, reduces unnecessary drug e"posure in

    healthy !olunteers, and increases impact for the replacement of certain bioequi!alence 2BF4

    studies with in !itro dissolution tests.


    The objecti!es of the BCS are 224

    V To impro!e the efficiency of the drug de!elopment and re!iew process by recommending a

    strategy for identifying e"pendable clinical bioequi!alence test.

    V To recommend a class of immediate%release 2#$4 solid oral dosage forms for which

     bioequi!alence may be assessed based on in !itro dissolution tests.

    V To recommend methods for classification according to dosage form dissolution along with

    the solubility/ permeability characteristics of the drug product.

    The BCS, which is based on scientific principles, presents a new paradigm in bioequi!alence.

    &ccording to the tenets of the BCS, certain drug products can be considered for bio%wai!ers

    2i.e., product appro!al based on in !itro dissolution tests rather than bioequi!alence studies in

    human subjects4. &t first, bio%wai!ers were only applied to scale%up and post appro!alchanges 2S=9&C4 234, but later the bio%wai!er principle was e"tended to the appro!al of new

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    generic drug products. &s a result, unnecessary human e"periments can be a!oided, and the

    cost of de!eloping generic products can be significantly lowered.

    #t pro!ides drug designers an opportunity to manipulate the structure or physicochemical

     properties of lead candidates to achie!e better deli!erabilityX.

    THE BIOPHARMACEUTICAL CLASSIFICATION SYSTEM (BCS) is an e"perimentalmodel that measures permeability and solubility under prescribed conditions. The original

     purpose of the system was to aid in the regulation of post%appro!al changes and generics,

     pro!iding appro!als based solely on in vitro data when appropriate. #mportantly, the system

    was designed around oral drug deli!ery since the majority of drugs are and remain orally

    dosed. Wai!ers, permission to skip in vivo  bioequi!alence studies, are reser!ed for drug

     products that meet certain requirements around solubility and permeability and that are also

    rapidly dissol!ing.

    Hore and more howe!er, the industry is using the BCS as a tool in drug product de!elop%

    ment. &s a simple e"ample, BCS can be used to flag drugs that should not be tested clinically

    unless appropriate formulation strategies are employed 2see Aigure 4.

    &s an e"ample, a BCS Class ## compound, permeable but relati!ely insoluble, would likely

    not be a good clinical candidate without the use of enhanced formulation techniques aimed at


    solubility or rate of  

    dissolution. 6arious schemes e"ist that attempt to funnel a gi!en &9# towards particular drug

    deli!ery techniques depending on the &9#s BCS category. Still, most approaches remain

    fragmented in their methodology, ignoring commercially and biologically important factors.

    The BCS can howe!er, when integrated with other information pro!ide a tremendous tool for 

    efficient drug de!elopment.

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      F"5&e 1

    7ne school of thought, !ery much endorsed by the authors, is that first in human 2A#-4 drugdosage forms should be designed to ma"imi'e bioa!ailability and that the A#- dosage form

    should be a logical step towards commerciali'ation and not simply a stop gap to facilitate

    data acquisition. This makes sense both economically and ethically.

    Aor BCS Class # molecules, A#- formulations are straight forward and may consist of 

    essentially the neat &9#. Aor other compounds, effecti!e dosage forms present greater 


    &lthough designed originally to classify &9#s as to their oral bioa!ailability, properly

    augmented, the BCS can be used as a key component of an algorithm to guide drug deli!ery

    system design for any route of administration. This notion has been elaborated on by a

    number of authors.


    Briefly, the BCS places a gi!en &9# in one of four categories depending on its solubility and

     permeability as they pertain to oral dosing 2see Aigure 4. & drug substance is considered

    highly solubleX when the highest clinical dose strength is soluble in )*+ m or less of aqueous media o!er a p- range of /0.* at

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    this assay ha!e de!eloped multiple approaches to alle!iate these issues but a re!iew is beyond

    the scope of this paper and the reader is encouraged to contact the !arious suppliers. &s a

    drug candidate mo!es

    up the de% !elopment

    ladder, de!elopers will

    often confirm and refine their  BCS assessments with

    increasingly comple" in vivo


    &n important subtlety here is

    that the BCS accounts for  

     potency in that solubility

    and permeability are

    relati!e to clinical dose.

    &gain, oral dosing is assumed in the testing design. So, for e"ample, a compound that has poor absolute solubility might parado"ically be classified as highly solubleX if it were a

    highly potent compound and the whole clinical dose was soluble in )*+ m.


    #t is commonly recogni'ed that most new drugs present formulation challenges. #n fact, older 

    drugs as compared to newer ones ha!e higher solubilities in general. 7ne reference noted that

    BCS Class ## compounds as a percentage of compounds under de!elopment had increased


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    Aor the majority of &9#s a solid oral dosage form 2S784 is the preferred option. Sometimes

    the physicochemical and physiologic mechanisms do not allow this and alternati!es are

     pursued such as suspensions or oral solutions. 7ther times, the target and other factors dictate

    that a non%oral dosage form is most sensible. F"amples include the local deli!ery of female

    hormones, nasal allergy preparations, and ocular therapeutics and combination productsaimed at prolonged drug release. #n all these cases, e!en though not orally dosed, the

    concepts inherent in the BCS can be important tools in dosage form design.


    -a!ing a pre%defined system in which one can make decisions based on data is necessary for 

    efficient drug de!elopment. #nputs into such a system include, in addition to BCS class, a

    detailed solubility profile, polymorph status, desired dosage form, target dose and dosing

    regimen, drug stability, F"cipients compatibility and knowledge of transporter and metabolic

     pathways. >on%technical factors that, as a practical matter, need to be considered are such

    things as cost, intellectual property and distribution chain limitations. #ntegration of these into

    a methodical systematic approach will ma"imi'e the chances of a successful outcome.

    &s $M8 dollars become e!er more scarce, it becomes increasingly e!ident that early

    consideration of as many factors as possible is the most efficient way to proceed. This is true

    independent of the route of administration. #n practice, this leads to the strategy of getting to

    A#- as quickly as possible with a formulation strategy that accounts for both physicochemical

     properties and physiologic influences.

    & complete set of algorithms co!ering the four classes and all possible dosage forms is well

     beyond the scope of this article. -owe!er, a few fundamental principles can be co!ered. Airst,it is critical to characteri'e your compound. =nderstanding the basic beha!iour of a gi!en

    compound in !arious sol!ents and across a range of p-s is fundamental to designing a dosage

    form. Aor instance, a compound soluble only at lower p-s will require a different formulation

    than one freely soluble at, for e"ample, p- 0. ikewise, a soluble yet impermeable compound

    will require yet another strategy. 6ery importantly, this is true whether one is administering

    the drug, for e"ample, #6 or orally. The implications to formulation are different for the dif%

    ferent routes of administration but the fact that these properties need to be accounted for is

    uni!ersal. #t is important that the drug de!eloper or the C$7 be equipped with a range of 

    technologies to address the !arious patterns that emerge. >othing wastes more time and

    money than trying to fit a drug to a specific preordained deli!ery technology.

    &rmed with the proper set of tools one can rapidly narrow down the potential approaches. Aor 

    the most part, all drug deli!ery strategies are trying to control drug e"posure. Host often, one

    is trying to ma"imi'e it o!er time and5or concentration but frequently goals also include

    e"tended release and5or site specific deli!ery. #n addition to the deli!ery goals, other 

    functions are often required such as &9# stabili'ation or taste masking as two e"amples.

    #n short, no one formulation approach will e!er satisfy all or e!en a substantial portion of 

    drug deli!ery demands.

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    Aor oral drug deli!ery, a simplified summary of approaches based on properties might look 

    like Table . Fach approach must then be tailored to meet the other demands of that particular 

    &9# and desired product profile.

      Table 1

    #f formulation conditions dictate that a non%oral dosage form be used, similar charts e"ist for 

    !irtually all routes of administration.

    Fach route of administration will of course ha!e different options but they are all ruled by the

    interplay of the

    drugs physi%


     properties and thelocal and systemic

     physiology they


    #ndependent of the final dosage form, ideal drug de!elopment in!ol!es an iterati!e process of setting goals, performing formulation work and de!elopmental stage appropriate testing.

    Farly on, for e"ample, after physicochemical e!aluations are complete, screening BCS testing

    and early polymorph screens might be performed. &fter thorough pre%formulation including

    solubility and stability testing, early formulations might again be screened for their impact on

    dissolution or bioa!ailability. This approach is repeated such that at each inflection point data

    is gathered to support the de!elopment plan. #n this way, A#- is achie!ed most efficiently and

    in such a way as to insure clinically rele!ant data is obtained.