Int. Res J Pharm. App Sci., 2013; 3(6):56-69 ISSN: 2277-4149 Omar Mady., 2013 56 International Research Journal of Pharmaceutical and Applied Sciences (IRJPAS) Available online at www.irjpas.com Int. Res J Pharm. App Sci., 2013; 3(6):56-69 MECHANISMS AND PERCENT OF DRUG RELEASE OF EACH NEW MATHEMATIC APPROACH Omar Mady,Ph.D. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Tanta, Tanta, Egypt. *Corresponding Author: Omar Mady; Email: Omer.Mady@gmx.at Abstract: Peppas and Sahlin model accounts for the coupled effects of Fickian diffusion and case II transport. By using the exponent coefficient (n) from Krosmeyer-Peppas model and substitution in Peppas-Sahlin model, the constants (K1&K2) could be calculated using different calculation methods. Matrix method is widely used for calculation of the kinetic constants which lead to calculate one constant value for each mechanism, for the whole drug release process. It was proved about the unacceptable points on using the kinetic constants (K1&K2) calculated by matrix solution method for comparison and also for calculation of the Fickian fraction release. Another mathematic method was applied for calculation of the kinetic constants (K1&K2) which is substitution method. The use of the substitution method gives the chance for calculation of the kinetic constants (K1&K2) at each unites time. As a result it could be calculate the amount of drug release % by each mechanism at each unites time and there is no need for further calculation for comparison like the Fickian fraction release. Also the substitution method may be, indicate the role of each drug release mechanism at each point especially because the comparison would be between the amount of drug release % by each mechanism at each unites time. Not only that but also the overlap, alternate, predominate and also combination of all drug release mechanisms at each unites time can be clearly observed which bring us to the realty of the drug release process which is a dynamic complex one. Key words: drug release mechanism, matrix solution, substitution solution, kinetic constant INTRODUCTION In the development of the pharmaceutical dosage forms, the providing of a particular drug release profile is highly desirable. 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. 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 1 . Different factors related to the drug can influence its release like kind of drug, its polymorphic form, crystallinety, particle size, solubility and its amount in the pharmaceutical dosage form 2-4 . A water soluble drug incorporated in a matrix is released mainly by diffusion, while for a low water soluble drug the self erosion of the matrix will be the principle release mechanism 1 . To compare dissolution profiles between two drug products, model dependent (curve fitting), statistic analysis and model independent methods can be used. Numerous methods are available to elucidate the dissolution data as a function of time but its dependence on the dosage form properties can be best deduced by using equations which mathematically translates the dissolution curves in the function of other parameters related to the delivery device. The best model for drug dissolution / release can be selected based on different criteria. The most common method used is the correlation coefficient r 2 to assess the fitting of a model equation 3 . Krosmeyer et al 5 , derived a simple relationship which described the drug release from a polymeric system. This relationship is very frequently used to describe the drug release from several different pharmaceutical modified release dosage forms 1 . To find out the release mechanism of the drug, the first 60 % of the drug release data should be fitted in the Krosmeyer-Peppas model. The drug release exponent (n) value is used to characterize different drug release mechanism. From cylinder shape matrices, when the value of (n) is 0.45 or less the drug release mechanism will be corresponding to Fickian diffusion mechanism. If value of (n) is < 0.85, the drug release mechanism will be considered as non-Fickian one and if it is exact 0.89 then the drug release is case II transport. In case of (n) is higher than 1 the release mechanism will be considering super case II transport 1 . An interesting model was developed by Peppas and Sahlin. This model accounts for the coupled effects of Fickian diffusion and case II transport 6-7 . By using the exponent coefficient (n) from Krosmeyer-Peppas model and substitution in Peppas-Sahlin model, the constants (K 1 &K 2 ) can be calculated. The values of K 1 indicates the contribution of diffusion (Fickian or case 1 kinetics) while the value of K 2 is associated with the dissolution as well as relaxation of the polymer chains 8 . Research Article