بررسي رابطه ساختمان داروهاي مختلف با سرعت رهش آنها از پليمر هيدروفيل

Quantitative relationship between chemical structure of drugs and the release rate from HPMC E4M matrices

Controlled drug release is vital for sustaining the appropriate blood levels. This necessitates a thorough study of drug release profiles. In this study quantitative relationships between chemical structure of drugs and their release from HPMC E4M were investigated using QSPR (Quantitative Structure -Property Relationship) technique. To this end, matrices containing 100 mg of the polymer and 100 mg of drug were prepared using a constant pressure for 12 drugs from different chemical groups and the release profiles were investigated at pH=6.8. Release parameters consisted of drug release rate constants calculated from various kinetic models of zero order, first order, Peppas, Higuchi and Weibull as well as dissolution efficiency, the amount of drug released within the first 8h and the time required for the release of 50% of drugs. Structural parameters were obtained from Molecular mechanics, Quantum mechanics, graph theoretical software packages and ACD log D suit. Stepwise regression analysis was used in Minitab statistical software in order to establish statistically significant relationships between each release parameter and structural descriptors. The resulting equations revealed that increasing the molecular size leads to decreased release rate and efficiency from HPMC E4M matrices. However the drug release rate increased with the increase of the drug solubility.