Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers. II. Effect of HPMC with different degrees of methoxy/hydroxypropyl substitution

Abstract

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different substitution degree (E4M, F4M, K4M) by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA) at different proportions (75:25, 50:50 and 25:75). The product (HCMMA) was dried either in a vacuum oven – OD copolymers – or freeze-dried—FD copolymers. HPMC E4M formulations showed the worst compaction properties. All mixtures presented a percentage of theophylline release between 47% and 32% at 1440 min. The drying methods employed had only influence over the drug release in E4M and K4M formulations, at higher proportions of HCMMA, showing the highest release the mixtures containing OD-HCMMA. Combinations of diffusion and erosion release mechanisms were found to matrix tablets. All mixtures with F4M did not modify relaxation rate constant values of Peppas and Shalin equation ( k r ) respect to F4M 100%. However, all mixtures with K4M showed the highest k r values, which decreased when HCMMA proportion decreased. Only K4M mixtures showed a different diffusion front movement than the other mixtures. The modulation of theophylline monoaxial release was obtained using a high percentage of HCMMA, and HPMCs with a substantial difference of hydroxypropyl groups (F4M and K4M or E4M).