INFLUENCE OF MOLECULAR-SIZE AND WATER SOLUBILITY OF THE SOLUTE ON ITS RELEASE FROM SWELLING AND EROSION CONTROLLED POLYMERIC MATRICES

The release of 23 drugs of various solubilities and molecular weights through matrices of hydroxypropylmethylcellulose (HPMC; matrix I) and a mixture (1:1) of HPMC and sodium carboxymethylcellulose (matrix II) was studied. Very soluble and soluble beta blockers and a freely soluble vitamin (thiamine hydrochloride) were released more slowly from matrix II than from matrix I due to complex formation between the cationic drug and the anionic polymer. For 15 of the drugs, the release rates from matrix II were much higher than from matrix I owing to the rapid erosion of the swollen gel of matrix II compared to matrix I. Increase in molecular weight (a parameter that may be indirectly related to the molecular size) decreased the release rate in a nonlinear manner from both the matrices for soluble (l-ephedrine and propranolol hydrochloride) and certain slightly soluble drugs (atropine and quinine sulfate, as well as acetazolamide, phenobarbital and erythromycin), and from matrix I alone for very soluble beta blockers. For methyltestosterone, erythromycin and diazepam, the release rates from matrix I are nearly the same, although their molecular weights and solubilities differ widely. When the release data (≤ 60%) was fitted to the simple power law equation, the mode of drug release from matrix land matrix II was non-Fickian and super case II type, respectively, for sparingly soluble, slightly soluble and very slightly soluble drugs. The study revealed that drugs falling into this category can be released at nearly zero-order rate through HPMC matrices. Since these matrices are prepared by direct compression, cellulose matrices may be preferred for oral controlled release formulations. © 1990.