ReviewModeling and comparison of dissolution profiles
Introduction
In vitro dissolution has been recognized as an important element in drug development. Under certain conditions it can be used as a surrogate for the assessment of Bioequivalence. Several theories/kinetics models describe drug dissolution from immediate and modified release dosage forms. There are several models to represent the drug dissolution profiles where ft is a function of t (time) related to the amount of drug dissolved from the pharmaceutical dosage system. The quantitative interpretation of the values obtained in the dissolution assay is facilitated by the usage of a generic equation that mathematically translates the dissolution curve in function of some parameters related with the pharmaceutical dosage forms. In some cases, that equation can be deduced by a theoretical analysis of the process, as for example in zero order kinetics. In most cases, with tablets, capsules, coated forms or prolonged release forms that theoretical fundament does not exist and some times a more adequate empirical equations is used. The kind of drug, its polymorphic form, cristallinity, particle size, solubility and amount in the pharmaceutical dosage form can influence the release kinetic (Salomon and Doelker, 1980; El-Arini and Leuenberger, 1995). A water-soluble drug incorporated in a matrix is mainly released by diffusion, while for a low water-soluble drug the self-erosion of the matrix will be the principal release mechanism. To accomplish these studies the cumulative profiles of the dissolved drug are more commonly used in opposition to their differential profiles. To compare dissolution profiles between two drug products model dependent (curve fitting), statistic analysis and model independent methods can be used.
Section snippets
Zero order kinetics
Drug dissolution from pharmaceutical dosage forms that do not disaggregate and release the drug slowly (assuming that area does not change and no equilibrium conditions are obtained) can be represented by the following equation:where W0 is the initial amount of drug in the pharmaceutical dosage form, Wt is the amount of drug in the pharmaceutical dosage form at time t and K is a proportionality constant. Dividing this equation by W0 and simplifying:where ft=1−(Wt/W0) and ft
Release profiles comparision
The parameters described above contribute with a little information to clarifying the release mechanism and should be used associated with each other or with some of the models previously referred.
Some methods to compare drug release profiles were recently proposed (CMC, 1995; Shah and Polli, 1996; Ju and Liaw, 1997; Polli et al., 1997; Fassihi and Pillay, 1998). Those methods were classified into several categories, such as:
- •
Statistical methods (Tsong and Hammerstrom, 1996) based in the
Conclusions
As it has been previously referred to, the quantitative interpretation of the values obtained in dissolution assays is easier using mathematical equations which describe the release profile in function of some parameters related with the pharmaceutical dosage forms. Some of the most relevant and more commonly used mathematical models describing the dissolution curves are shown in Table 2.
The drug transport inside pharmaceutical systems and its release sometimes involves multiple steps provoked
References (70)
- et al.
Influence of shape factors on kinetics of drug release from matrix tablets. I. Theoretical
J. Pharm. Sci.
(1974) - et al.
Influence of shape factors on kinetics of drug release from matrix tablets. II. Experimental
J. Pharm. Sci.
(1974) - et al.
Investigation of factors influencing release of solid drug dispersed in inert matrices. III. Quantitative studies involving the polyethylene plastic matrix
J. Pharm. Sci.
(1966) - et al.
Investigation of factors influencing release of solid drug dispersed in inert matrices. IV. Some studies involving the polyvinyl chloride matrix
J. Pharm. Sci.
(1966) - et al.
Investigation of factors influencing release of solid drug dispersed in inert matrices. II. Quantification of procedures
J. Pharm. Sci.
(1966) - et al.
Dissolution properties of praziquantel–PVP systems
Pharm. Acta Helv.
(1998) - et al.
Mathematical modeling of drug release from hydroxypropylmethylcellulose matrices: effect of temperature
Int. J. Pharm.
(1991) - et al.
Establishment of sink conditions in dissolution rate determinations - theoretical considerations and application to nondisintegrating dosage forms
J. Pharm. Sci.
(1967) Rate of release of medicaments from ointment bases containing drugs in suspension
J. Pharm. Sci.
(1961)Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices
J. Pharm. Sci.
(1963)