# 2018 Riphah Institute of Pharmaceutical Sciences Semester – 7

2018

Riphah Institute of Pharmaceutical Sciences

Semester – 7 | Section – A | Submission Date: 19.september.2018

Biopharmaceutics Assignment

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CONTENTS

Question Number Question statement

01 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: 01

Drug Absorption

Drug 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 form

1- Pharmaceutics related factor2- Patient related factor

Physicochemical Properties of Drugs

Sr # Physicochemical Properties of drug

01 Drug solubility and dissolution rate

02 Salt form of drug

03 Surface Area and Particle size

04 Lipophilicity of the drug

05 Pka of the drug and pH

06 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 pH

The 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 GIT

The 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 ABSORPTION

Highly 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: 02

Integration steps of both Cero and First order reactions

Zero Order Reaction

Differential Representations:

The differential equation describing first-order kinetics is given below:

Rate= -d

The differential equation describing first-order kinetics is given below:

Rate= ? dAdt = k An

In zero order n=0

Rate= ? dAdt = k A 0= k = constant ……………….. (i)

Integral representation:

The differential equation for zero order is

Rate= ? 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 time

T = time

40671752092960A0 = initial amount of drug at time “0”

k° = zero order elimination rate constant

The 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 Equation

Differential representation:

The differential equation describing first-order kinetics is given below:

Rate= ? dAdt= k An

In first order n=1

Rate=?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 time

A0 = amount of drug at time “0”

T = time

K = first order elimination rate constant

The rate constant, k, has units of sec-1.

This equation can also be written in the following form:

370522522860lnA = -kt + lnA0

A plot of lnA versus t will yields a straight

line with the slope –k.

ANSWER: No: 03

NON COMPENDIAL METHODS OF DISSOLUTION

Rotating 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 Method

Most 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 Cell

Static 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 1977

Petrucci, 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, 2007

Leon shargel Andrew B.C seventh edition non compendia methods of dissolution

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