This document discusses physicochemical and biological considerations in the design of modified release dosage forms. It covers topics like aqueous solubility, partition coefficient, drug stability, protein binding, molecular size and diffusivity, absorption, distribution, metabolism, elimination, biological half-life, and side effects and safety. The document was submitted by a group of 12 pharmacy students at Universal Medical and Business College as an assignment on industrial pharmacy. It references textbooks and websites for its sources.

1. UNIVERSAL MEDICAL AND
BUSINESS COLLEGE
DEPARTMENT OF PHARMACY
SECTION A GROUP 2
INDUSTRIAL PHARMACY ASSIGNMENT 2
SUBMITTED TO MR
SUBMITTED DATE : FEB 14 2023

2. Physicochemical and
biological consideration
in the design of
modified release
dosage form

3. Physicochemical consideration
1, AQUEOUS SOLUBILITY
 It is an important consideration in its biological performance as a SDRF.
 Aqueous solubility of a drug exerts its control on the absorption process in two ways-
1, By influence on the dissolution rate of a compound which establish the drug
concentration in solution and the driving force for tissue permeation.
2, By its effect on the ability of the drug to penetrate tissues which is determined in part
by its solubility in the tissue.
 Dissolution rate is related to aqueous solubility which is given by NOYES-WHITNEYS
EQUATION.
dc/dt=KDA.CS

4. 2, PARTITION COEFFICIENT
 between the time that a drug is administered and the time it is eliminated from the
body.
 It diffuse through a variety of biological membranes that act primarily as lipid like
barriers.
 The major criteria in evolution of the ability of a drug to penetrate these lipid
membranes is it apparent oil-water partition coefficient defined as :-
K=Co/Cw

5. 3, DRUG STABILITY
 In oral dosage form, loss of drug through acid hydrolysis or metabolism in GIT.
 A drug in solid state undergoes degradation at much slower rate than drug in
suspension/solution.
 Drugs with low aqueous solubility have low dissolution rate and usually suffer oral
bioavailability problems.
 Aqueous solubility of weak acids and base is governed by pka value and PH of the
medium.

6. 4, PROTEIN BINDING
 Distribution of drug in to extra space is governed by dissociation of drug from protein.
 Drug protein complex acts as reservoir in the vascular space for sustained drug
release to extra vascular tissue for drug exhibiting high degree protein binding.
 Some drug shows higher degree protein binding ex-Diazepam shows greater than 95%
protein binding.

7. 5, MOLECULAR SIZE AND DIFFUSIVITY
 Ability of drug to diffuse through membrane is called as diffusivity, is a function of
molecular size.
 In most of polymers, its possible to logD empirically to some function of molecular
size as
LogD=Sv log V+Kv=-Sm log M+Km

8. Biological consideration
1, ABSORPTION
 Rate, extent and uniformity of absorption are the important factors when considering
sustained release.
 Since the rate limiting step in drug delivery from a sustained release is its release from
dosage form, rather than absorption a rapid release is essential if the system is
successful.

9. 2, DISTRIBUTION
 The distribution of drug in to vascular and extra vascular spaces in the body is an
important factor in its overall elimination kinetics.
 This influences the formulations of that drug in to a sustain release, primarily by
restricting the magnitude of release rate and dose size.
 Volume of distribution obeys only one compartment model
v= dose/Co

10. 3, METABOLISM
 Metabolism is the conversion of a drug to another chemical form and this is
considered in the design of sustained release system for the drugs.
 Factors associated with metabolism
1,ability of the drug to induce or inhibit enzyme synthesis.
2,fluctuating drug blood level and first pass metabolism. Ex- nitroglycerine

11. 4, ELIMINATION AND BIOLOGICAL HALF LIFE
 The rate of elimination of drug Is described quantitatively by its biological half life.
t½= 0.693 v/cls
 Drug having shorter half life requires frequent dosing. Making it desirable to develop
SDRS. this will be opposite for drugs with higher half lives.
 Drug with half life less than 2hrs and those with more than 8hrs should not be used.

12. 5, SIDE EFFECTS AND SAFETY CONSIDERATION
 Minimizing side effect for a particular drug done by controlling its plasma
concentration and using less total drug over time course of therapy.
 To measure margin of safety of drug its therapeutic index is considered.
TI=TD50/ED50

13. Reference
• Book of dosage form design consideration written by Rakesh K. Tekade in
2018
• Book of design of controlled released drug delivery system written by
Bhaskara R. JASTI
• http://accesspharmacy.mhmedical.com

14. Group members
1, MERON TESHOME…………………………… .041/12
2, NARDOS TEGBAR…………………………….. 047/12
3, YORDANOS FIKRE…………………………….066/12
4, MAHLET MOGES………………………………033/12
5, MENGESTU WONDE…………………………..040/12
6, MELAT HABTAMU…………………………….039/12
7, FOZIA WORKU………………………………....021/12
8, RAHWA GIRMAY……………………………….048/12
9, REDIET YESHANEH…………………………....049/12
10, LYDIA BIRUK………………………………….031/12
11, ATSEDE FELEKE……………………………...011/12
12, ABREHAM GETACHEW……………………...004/12