2018Riphah Institute of Pharmaceutical SciencesSemester – 7 | Section – A | Submission Date: 19.september.2018Biopharmaceutics AssignmentType the abstract of the document here. The abstract is typically a short summary of the contents of the document.
Type the abstract of the document here. The abstract is typically a short summary of the contents of the document.CONTENTS Question Number Question statement01 Explain how pH partition theory provides a basic framework for understanding drug absorption?02 Provide complete Integration Steps of both zero and First order equations?03 Describe the Non compendia methods of dissolution with diagrams? Answer: No: 01Drug AbsorptionDrug absorption is defined as the process of movement of unchanged drug from the sie of admiration to systemic circulation.Factors influencing GI absorption of a drug from its dosage form1- Pharmaceutics related factor2- Patient related factor Physicochemical Properties of DrugsSr # Physicochemical Properties of drug01 Drug solubility and dissolution rate02 Salt form of drug03 Surface Area and Particle size04 Lipophilicity of the drug05 Pka of the drug and pH06 Drug stability PH Partition Theory The Theory states that those drugs having molecular weight greater than 100 which are primarily transported across the bio-membrane by passive diffusion, there absorption is governed by The dissociation constant (pka) of the drug.The lipid solubility of the unionized drug.
The PH at the absorption site.PH partition theory to influence of GI and the drug pka on the extent of drug absorption.PH partition theory of drug absorption is based on the assumption that the GIT is a simple lipid barrier to the transport of drugs and chemicals. Accordingly the unionized form of an acidic drug or basic drug, if sufficiently lipid soluble is absorbed but the ionized form is not.Drug pka and gastrointestinal pHThe fraction of drug in solution that exists in the unionized form is a function of both dissociation constant of the drug and the PH of the solution.The dissociation constant is often expressed for both acid and base as pka.
The lower the pka of an acidic drug, the stronger the acid i.e. greater the proportion of ionized form at a particular PH. The higher the pka of basic drug , the stronger the base.
The relative amount of ionized and unionized drug in solution at particular pH and the percent of drug in solution at this pH can be determined by Henderson Hasselbach equation.For an acid Pka-PH = log (fu/fi)For a base Pka-PH= log (fi/fu) The pH Range in GITThe pH range in GIT from 1-8 that of the stomach is from 1-3 and of the intestine 5-8.These factors minimize the need for large fraction of the drug to be in an unionized form in the small intestine.Strong acids are ionized throughout the GIT and are poorly absorbed.
LIPOPHILICITY AND DRUG ABSORPTIONHighly lipid soluble drugs are generally absorbed while lipid insoluble drugs are generally poorly absorbed. Certain drugs are poorly absorbed after oral administration even though they are largely unionized in the small intestine (low lipid solubility of the uncharged molecule may be the reason). Lipophilic nature of a drug and its partition coefficient between a fat like solvent and water or an aqueous buffer.
Polar molecules such as gentamicin heparin are poorly absorbed after oral administration and must be given by injection. Lipid soluble drug with favorable partition coefficient are usually well absorbed after oral administration. The lipid solubility of drug is determined from its oil/water partition coefficient value. This value is a measure of the degree of distribution of drug between one of the several organic, water immiscible, lipophillic solvent.Answer No: 02Integration steps of both Cero and First order reactionsZero Order ReactionDifferential Representations:The differential equation describing first-order kinetics is given below:Rate= -dThe differential equation describing first-order kinetics is given below:Rate= ? dAdt = k AnIn zero order n=0Rate= ? dAdt = k A 0= k = constant ………………..
(i)Integral representation:The differential equation for zero order isRate= ? dAdt= k ……………………………………. (ii)By rearranging the equation:d A = – k dt ………………………………………..
(iii) integrate both side of equation:A°AdA = – 0tk dt …………………… (iv) A – A0 = – kt ……….…………………(v)By rearranging the equation the integrated form for the zero order will become; A = – kt + A0………………………….(vi)So, therefore A = – kt + A0 (integrated form)Where,At = amount of drug at any timeT = time40671752092960A0 = initial amount of drug at time “0”k° = zero order elimination rate constantThe rate constant, k, has units of mole L-1 sec-1.A plot of A versus t will yield a straight line with the Slope –k. First Order EquationDifferential representation:The differential equation describing first-order kinetics is given below:Rate= ? dAdt= k AnIn first order n=1Rate=?dAdt= k A 1 =kA………………..
(i)The “rate” is the reaction rate (in units of molar/time) and k is the reaction rate coefficient (in units of 1/time).Integral representation:First write the differential equation;Rate= ? dAdt= k A…………………………… (ii)Rearranging the above equation: Rate= ? dAA = kdt ……………………………. (iii)Integrate the both side of equation:A°AdAA = – t°tk dt …………………… (iv)A°A1AdA = – t°tk dt …………………… (v)According to calculus rule:1x = ln (x)So equation (v) will become: lnA – lnAo = -k dt…………………….. (vi)by rearranging the equation;lnA = -k dt + lnAo …………………….
. (vii)So, therefore ln A = -k dt + ln Ao (integrated form)This is the final form of the integrated rate law for a first-order reaction. Where,At = amount of drug at any timeA0 = amount of drug at time “0”T = timeK = first order elimination rate constantThe rate constant, k, has units of sec-1.
This equation can also be written in the following form:370522522860lnA = -kt + lnA0A plot of lnA versus t will yields a straight line with the slope –k. ANSWER: No: 03NON COMPENDIAL METHODS OF DISSOLUTIONRotating bottle method The rotating bottle method was mainly for controlled release beads.For this purpose the dissolution medium may be easily changed.such as an artificial gastric juice to artificial intestinal juice.The equipment is consists of a rotating rack that holds the sample drug product in bottles.The bottles are capped tightly and rotated at 37 degree temperature bath.
At a various time the samples are removed from the bottle decanted through a 40 mesh screen and the residue are assayed. An equal amount of fresh medium is added to remaining drug residue within the bottle and dissolution is continued.A dissolution test with ph 1.5medium for 1 hour ph 2.5 medium for next hour followed by ph 4.5 medium for 1.
5 hour and ph 7.5 medium for 2 hours was recommended to stimulate the gastrointestinal tract .Main disadvantage is that this procedure is manual.
Intrinsic Dissolution MethodMost methods of dissolution deals with the finished drug product. A new drug may be tested for dissolution without the effect of excipients.The dissolution of drug powder by maintaining a constant surface area is called intrinsic dissolution.Intrinsic dissolution can be expressed as mg/min.The basket method is adapted to test dissolution of powder by placing the powder in a disk attached with a clipper to the bottom of the basket.Peristalsis Method The peristalsis method attempts to stimulate the hydrodynamic conditions of gastrointestinal tract in an in vitro dissolution device.The apparatus consists of a rigid plastic cylindrical tubbing fitted with a septum and rubber stopper at both ends.
The dissolution chamber consist of a space between the septum and the lower stopper.The apparatus is placed in a beaker containing the dissolution mrdium.The dissolution medium is pumped with peristalsis action through the dosage form.Diffusion CellStatic and flow through diffusion cells are available to characterize in vitro drug release and drug permeation kinetics from topically applied dosage form e.g ointment creamThe franz diffusion cell is a static diffusion system that is used for characterizing drug permeation through skin model.The source of skin may be human skin or animal skin .
each skin site has different drug permeation qualities.The skin is mounted on the Franz diffusion cell system.The drug prpduct is placed on the skin surface and drug permeates across the skin into receptor fluid compartment that may be sampled at various times.The Franz diffusion cell system is useful for comparing in vitro drug release profiles and skin permeation characteristics to aid in selecting an appropriate formulation that has optimum drug delivery.
References Shargel L., Andrew B.C., Fourth edition “Physiologic factors related to drug absorption” http://pharmawiki.in/ppt-ph-partition-theory/tment’ and Research and Development Laboratory,2 Astra Ldkemedel AB, S-151 85 Sodertdlje, Sweden, and Department of Microbiology, Institute of Pharmacy, University of Oslo, Oslo, Norway3 Received for publication 27 June 1977Petrucci, Ralph H., William S.
Harwood, Geoffrey Herring, and Jeffry D. Madura. General Chemistry: Principles ; Modern Applications. Ninth ed. Upper Saddle River, N.J.: Pearson Education, 2007Leon shargel Andrew B.C seventh edition non compendia methods of dissolution The End
