COMPARATIVE DISSOLUTION STUDIES FOR ACECLOFENAC MARKETED DOSAGE FORMS
M.pharmacy II year
Annamacharya college of pharmacy,
Rajampet, kadapa dist, a.p, india
INTRODUCTION TO DISSOLUTION
"Dissolution is defined as the process by which solid substances enters in solvent to yield a solution. Stated simply, dissolution is the process by which a solid substance dissolves. Fundamentally, it is controlled by the affinity between the solid substance and the solvent.. "The physical characteristics of the dosage form, the wettability of the dosage unit, the penetration ability of the dissolution medium , the swelling process, the disintegration and the deaggregation of the dosage forms are few of the factors that influence the dissolution characteristics of drugs.
Drug dissolution testing is a quantitative analytical technique for assessing drug release from pharmaceutical products, in particular solid oral dosage forms such as tablets and capsules. The reason for conducting the test is that generally for a drug to be absorbed, usually from the gastrointestinal tract, the drug should be in solution form. Thus evaluation of dissolution becomes useful and necessary.
There is ample evidence in the literature to indicate that drug dissolution is critical for drug absorption into the systemic circulation (“bloodstream”) or human body in general. In this respect, one may consider a dissolution test as a surrogate marker of availability of drug for systemic circulation. Commonly, this availability of drug in the body is known as bioavailability and is defined as, the rate and extent of absorption of a drug into the systemic circulation. The rate and extent of drug absorption are generally represented by maximum observed concentration (Cmax) of a drug in blood and area under the drug concentration verses time curve (AUC), respectively. In general, drug dissolution results are compared to these in vivo parameters.
REFERENCE ID: PHARMATUTOR-ART-1666
B. LAWS GOVERNING DISSOLUTION1
The rate of dissolution is described by
1. NOYES-WHITNEY EQUATION
dW DA ( Cs - C )
----- = ------------
dt is the rate of dissolution.
A is the surface area of the solid.
C is the concentration of the solid in the bulk dissolution medium.
Cs is the concentration of the solid in the diffusion layer surrounding the solid.
D is the diffusion coefficient.
L is the diffusion layer thickness.
As can be inferred by the Noyes-Whitney equation, the rate of dissolution may be modified primarily by altering the surface area of the solid. The surface area may be adjusted by altering the particle size. The rate of dissolution may also be altered by choosing a suitable polymorph of a compound. Specifically, crystalline forms dissolve slower than amorphous forms. Also, coatings on a tablet or a pellet may act as a barrier to reduce the rate of dissolution. Coating may also be used to modify where dissolution takes place.
2. FICK’S FIRST LAW
Fick's first law of diffusion states
Rate of solution =
D is the diffusion coefficient,
A the surface area,
Cs the solubility of the drug,
Cb the concentration of drug in the bulk solution, and
h the thickness of the stagnant layer.
If Cb is much greater than Cs then we have so-called "Sink Conditions" and the equation reduces to
Rate of solution =
Surface area, A
The surface area per gram (or per dose) of a solid drug can be changed by altering the particle size. Methods of particle size reduction include mortar and pestle, mechanical grinders, fluid energy mills, solid dispersions in readily soluble materials (PEG's).
Diffusion layer thickness, h
This thickness is determined by the agitation in the bulk solution. In vivo we usually have very little control over this parameter. It is important though when we perform in vitro dissolution studies because we have to control the agitation rate so that we get similar results in vitro as we would in vivo.
Plot of Concentration versus Distance for Dissolution into a Reactive Medium
The apparent thickness of the stagnant layer can be reduced when the drug dissolves into a reactive medium. For example, with a weakly basic drug in an acidic medium, the drug will react (ionize) with the diffusing proton (H+) and this will result in an effective decrease in the thickness of the stagnant layer.
The effective thickness is now h' not h. Also the bulk concentration of the drug is effectively zero. For this reason weak bases will dissolve more quickly in the stomach.
Diffusion coefficient, D
The value of D depends on the size of the molecule and the viscosity of the dissolution medium. Increasing the viscosity will decrease the diffusion coefficient and thus the dissolution rate. This could be used to produce a sustained release effect by including a larger proportion of something like sucrose or acacia in a tablet formulation.
Drug solubility, Cs
Solubility is another determinant of dissolution rate. As Cs increases so does the dissolution rate. We can now look at ways of changing the solubility of a drug.
C. THEORIES OF DISSOLUTION1
Several theories to explain drug dissolution have been proposed. Some of the important ones are
(i) The Diffusion layer model / Film Theory
This model assumes that a layer of liquid, H cm thick, adjacent to the solid surface remains stagnant as the bulk liquid passes over the surface with a certain velocity. The reaction at the solid/liquid interface is assumed to be instantaneous forming a saturated solution, C s , of the solid in the static liquid film. The rate of dissolution is governed entirely by the diffusion of the solid molecules from the static liquid film to the bulk liquid according to Fick’s first law:
J = - Df dc / dx
J is the amount of substance passing perpendicularly through a unit surface area per time,
Df ,is the diffusion coefficient and dc / dx, is the concentration gradient.
After a time t, the concentration between the limit of the static liquid layer and the bulk liquid becomes C t . Once the solid molecules pass into the bulk liquid, it is assumed that there is rapid mixing and the concentration gradient disappears.
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