Modulation of in-vitro drug-release from a HPMC matrix system: Potential role of a disintegrant

Sanjay Wagh, Jayanthi Suryakumar


The objective of the current study was to investigate the role of disintegrants in modulation of drug release from HPMC-based hydrophilic matrices.  The polymer matrices of a water-soluble drug, Propranolol hydrochloride, were prepared in combination with different disintegrants by wet-granulation approach. The widely used superdisintegrants like crospovidone (CP), croscarmellose sodium (CCS), calcium carboxymethyl cellulose (CaCMC) and sodium starch glycolate (SSG) were investigated for their potential role as release modifiers. The polymer-disintegrant combinations were evaluated for in-vitro drug-release behaviour at various pH conditions coupled with determination of swelling behaviour and gel properties of matrices through texture analysis. The polymer-disintegrant combinations provided control over initial release rate and also exhibited complete drug release over 24 h. The work of penetration of hydrogels after 24 h dissolution study revealed that formulation with croscarmellose sodium showed complete relaxation of gel which fostered the complete drug release. Drug-release from the developed combination matrices was observed to be primarily Fickian diffusion based, except for combination of HPMC- sodium starch glycolate based matrices, where non-Fickian behaviour was observed. Barring sodium starch glycolate, all other polymer-disintegrant combinations provided pH-independent drug release. The accelerated stability studies of optimized HPMC-disintegrant matrix system were also satisfactory.  The results of this study suggest that a suitable disintegrant when used in combination with HPMC, could modulate the drug-release and also synergize the release-controlling properties of hydrogel matrix systems. These findings can certainly be applied to develop controlled-release hydrogel matrix system of other highly water-soluble drug candidates, and hold a great potential in development of cost-effective and stable HPMC-matrix systems with customized drug-release behaviour.  


Propranolol hydrochloride, hydrophilic matrices, swelling, disintegrant, release kinetics.

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