Effect of physico chemical properties on sustained and controll ed

1. EFFECT OF PHYSICO-CHEMICAL
PROPERTIES ON SUSTAINED AND
CONTROLLED RELEASE TABLET

2. WHAT IS DRUG DELIVERY SYSTEM
The term “drug delivery systems’’ refer to the technology utilized to present the drug to the
desired body site for drug release and absorption.

3.  SUSTAINED RELEASE
It indicates an initial release of drug sufficient to provide a therapeutic dose soon after
administration and then a gradual release over extended period of time.
Example:- Nifedipine, Carbamazipine.
ADVANTAGE
. The major advantage is that there is a reduction in the frequency of drug administration,
while using such technique.
. patient compliance can improved, and drug administration can be made more convenient as
well.
. This technique ultimately maximizes the bioavailability of the drug in minimum dose.
. The safety margin of high- potency drugs can be increased, and the incidence of both local
and systemic adverse effect can be reduced by formulation in an extended actin form.
DISADVANTAGE
. Administration of sustained release medication does not permit the prompt termination of
therapy.
. The physician has less flexibility in adjusting dosage regimens. This is fixed by the dosage
form design.

4.  CONTROLLED RELEASE
Dosage forms release drug at a constant rate and provide plasma concentration that remain invariant with
time.
Example:-
ADVANTAGE
. Improve patient compliance.
. Reducing dosing frequency.
. More constant and prolong therapeutic effect.
. Reduction in health care cost.
. Better drug utilization.
. Reducing the incidence and intensity of adverse effect and toxicity.
. Controlled rate and site of release.
. Enhance bioavailability.

5. DISADVANTAGE
. Dose dumping.
. Reduced potential for accurate dose adjustment.
. Need of additional patient education.
. Stability problem

6.  The difference between controlled release and sustained release,
. Controlled drug delivery- which delivers the drug at a pre determined rate for a specified
period of time
. Controlled release is perfectly zero order release that is the drug release over time
irrespective of concentration.
. Sustain release dosage form- is defined as the type of dosage form in which a portion i.e.
(initial dose) of the drug is released immediately, in order to achieve desired therapeutic
response more promptly, and the remaining (maintenance dose) is then released slowly there
by achieving a therapeutic level which is prolonged, but not maintained constant.
. Sustained release implies slow release of the drug over a time period. It may or may not be
controlled release.
NOTE:- Disintegration test is not performed for controlled & sustained release tablets.

7.  Physico-chemical properties of sustained and controlled release tablet
 It is the study of physical properties of drug which can effect the chemical properties of drug.
 Their are various Physico-chemical properties like :-
• Aqueous solubility.
• partition coefficient.
• Drug stability.
• Protein binding.
• Molecular size and diffusivity.
• Pka determinations
• Dissolution

8.  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.
• Temperature also effect the solubility of drug if temperature is increase so solubility will increase and if
temperature will decrease so solubility will decrease.
 PARTITION COEFFICIENT
• It is define as the ratio of un-ionized drug distributed between the organic and aqueous phase
equilibrium.
• 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 co-efficient, defined as-
P=Co/Cw

9. Where,
Co= equilibrium concentration of all forms of drug in organic phase.
Cw= equilibrium concentration of all forms of drug in an aqueous phase.
 DRUG STABLITY
• In oral dosage forms, loss of drug through acid hydrolysis or metabolism in GIT.
• A drug in solid state undergoes degradation at much slower rate that drug in suspension/solution.
• Drug 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.
 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 release to extra vascular tissue for
drug exhibiting high degree protein binding.
• Some drugs shows higher degree protein binding ex- diazepam shows greater that 95%protein binding.

10.  MOLECULAR SIZE & 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 log D empirically to some function of molecular size as-
Log D=-Sv log V + Kv = -Sm log M + Km
Where,
V= molecular volume
Sv, Kv Km are constants
Value of D is related to size and shapes of drugs.
 Pka determination
• Determination of the dissociation constant for a drug capable of ionization within a pH range 1 to 10 is
important since solubility, and consequently absorption, can be altered by orders of magnitude with
changing in Ph .
• Henderson-Hasselbalch equation provides an estimate of the ionized and un-ionized drug concentration at a
particular pH .

11. For basic compounds:
pH= pKa + log
𝒊𝒐𝒏𝒊𝒛𝒆𝒅 𝒅𝒓𝒖𝒈
[𝒖𝒏𝒊𝒐𝒏𝒊𝒛𝒆𝒅 𝒅𝒓𝒖𝒈]
For acidic compounds:
pH= pKa + log
𝒖𝒏 𝒊𝒐𝒏𝒊𝒛𝒆𝒅 𝒅𝒓𝒖𝒈
𝒊𝒐𝒏𝒊𝒛𝒆𝒅 𝒅𝒓𝒖𝒈
 DISSOLUTION
• Dissolution rate is related to aqueous solubility which is given by NOYES-WHTNEY’S EQUATION.
𝒅𝒄
𝒅𝒕
=
𝑫𝑨𝑲(𝑪𝒔−𝑪𝒃)
𝑽𝒉
Where,
𝑑𝑐
𝑑𝑡
= dissolution rate.
D= Diffusion constant.
A= Total surface area of drug particle.
K= Partition coefficient.
Cs - Cb =concentration gradient for diffusion of drug.
V = volume of dissolution medium.
h = thickness of the stagnant layer.