2018

Riphah Institute of Pharmaceutical Sciences

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

BiOPharmaceutics Assignment

This includes PH Partition Theory, Complete integration steps of Zero and First Order Kinetics and Non compendia’s methods of dissolution. (Chapter # 02)

Submitted To: Dr. Muhammad Mohsin Ansari

Submitted By: Ishrat Fatima

CMS # 16875

Section/ Semester: 7th ‘A’

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)

Slope = -k

By rearranging the equation:

Concentration (mg/ml)

d A = – k dt ……………………………………….. (iii)

integrate both side of equation:

A°AdA = – 0tk dt …………………… (iv)Time (hr)

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

A0 = 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

Slope = -k

ln A

K = first order elimination rate constant

The rate constant, has units of sec-1

This equation can also be written in the following form:

LnA =-kt + ln A 0

Time

A plot of ln A versus t will yields a straight line with the slope –k.ine with the slope –k.

ANSWER: No: 03

NON COMPENDIAL METHODS OF DISSOLUTION

Rotating bottle method

This bottle was suggested in National Formulary.

This method was mainly for controlled released beads.

Temperature is 37?C in whole working.

Construction:

One system drive

One clear acrylic water bath.

Heater/ Circulator or one clear acrylic water bath.

One stainless steel drive bar with 14 positions.

20 standards 100 mL test bottles with caps.

Five Decant caps with 40- mesh screen.

Working:

Add tablets or capsules and extracting fluid to the standard test bottle.

Place the apparatus in the water bath.

Turn on the Rotating Bottle Apparatus.

Adjust the speed between 10 rpm and 60 rpm.

Then After appropriate time the bottles stop to rotating.

Remove the apparatus from the water bath and remove the bottles from the clips.

Replace the standard caps with 40-mesh screen caps.

Add extracting fluid to the residue.

Then replace the 40- mesh screen caps with the standard caps.

Carefully place the apparatus in the water bath.

Press RUN to continue the test. Then press STOP after completing the test.Disadvantages:

This method is manual and tedious.Intrinsic Dissolution method:

Most of the methods for dissolution test is done with a finished drug product. Sometimes a new drug may be tested for dissolution without the effect of excepients. The dissolution of a drug powder by maintaining a constant surface area is called intrinsic dissolution.

This is expressed as mg/cm2/min.

In this method, 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.

Construction:

Holder

Nylon Screws

Handle Bar

Punch

Surface plate

Stainless Bolts

Working:

First weight the material on a paper in a weighing balance.

Then place this weigh powder into the die cavity.

Compress the powder with the hydraulic press for one inute.

Remove all powder from the die.

Set the assembly.

There will be no rotation during process.

Air bubbles also be removed during the whole working.

Perform the test as written in the monograph.

Sink conditions should be maintained during the test.

The intrinsic dissolution rate, we plot the graph commulative amount of test powder versus time.

Time until 10% drug is dissolved.

Intrinsic dissolution rate is determined by the slope.

PERISTALSIS METHOD:The peristalsis method done to simulate the hydrodynamic conditions of the gastrointestinal tract.Construction and working:Rigid plastic cylindrical tubing fitted with a septum and rubber stoppers at both ends.

The dissolution chamber consists of a space between the septum and the lower stopper.

The apparatus is placed in a beaker containing the dissolution medium.

The dissolution medium is pumped with peristaltic action through the dosage form.

DIFFUSION CELLS:Static flow-through diffusion cells are commercially available in vitro drug release and drug permeation kinetics from topically applied dosage form (eg, ointment, cream) or transdermal drug product.

The Franz diffusion cell is a static diffusion system that is used for drug permeation through a skin model

182880012700

The source of skin may be human cadaver skin or animal skin (eg, hairless mouse skin).

The skin is mounted on the Franz diffusion cell system.

The drug product (eg, ointment) is placed on the skin surface and the drug permeates across the skin into a receptor fluid that may be sampled at several times.

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

The End