Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers: Effect of HPMC of different viscosity grades

• Published in: International journal of pharmaceutics 2008-03, Vol.351 (1), p.61-73
• Main Authors: Escudero, J.J., Ferrero, C., Jiménez-Castellanos, M.R.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers - chemistry; Drug delivery system; Freeze Drying; General pharmacology; Hydroxypropyl methylcellulose; Hydroxypropylcellulose-methyl methacrylate; Hypromellose Derivatives; Medical sciences; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Methylmethacrylate - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Porosity; Release modulation; Tablets; Theophylline; Theophylline - chemistry; Viscosity; Water - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2007.09.031

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different viscosity grade by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA). The drug released could be control by both mechanisms, the swelling rate from the hydrophilic matrices, and the porosity, tortuosity and water uptake capacity from inert matrices. The effects of drying methods, presence or absence of viscosity (HCMMA in relation with HPMC), proportion of two polymers and different viscosity grade of HPMC were studied. It was observed that the mixtures with FD-HCMMA needed less pressure, presented higher plasticity and their tablets were easier to obtain compared with OD-HCMMA mixtures. Only FD-HCMMA:K100M mixtures did not show any differences in the percentage of theophylline released when FD-HCMMA proportion changed ( f 2 > 95). All mixtures show double release mechanism, diffusion and erosion from the gel layer, but with higher contribution of the relaxation factor than on HPMC tablets. For the different mixtures HCMMA–HPMC, it is possible to see fronts movement profiles similar to swellable matrices. The results demonstrate that the use of high viscosity differences of HPMC or 50% HCMMA or above was required to produce modifications on theophylline monoaxial release modulation.