The performance of HPMC matrix tablets using various agglomeration manufacturing processes

Abstract

Context: The flow and compaction properties of a compaction mixture or powder and the drug-release profile of final tablets are important critical quality attributes (CQAs) that have an impact on the overall performance of hydrophilic matrix tablets. The selection of granulation method can importantly affect these CQAs.Objective: This study investigates various agglomeration methods of sustained-release formulation using HPMC K4M as a release polymer with various wet- and dry-granulation techniques.Materials and methods: Flow properties were determined using flow time, angle of response, and the Carr index. Compaction properties were evaluated using “out of die” Heckel model. Release of carvedilol was tested as 12-h drug-dissolution profile.Results and conclusion: Compression mixtures made using the wet-granulation method exhibit better flow and compression properties than compression mixtures made using the dry-granulation method. The direct compression method proved to be the least appropriate manufacturing method because the compression mixture has very poor flow and the lowest compressibility/compactibility index. The choice of granulation technique significantly influences the swelling behavior and drug-dissolution profile of the final matrix tablets, also resulting in dissimilar release profiles. The choice of granulation method has the greatest influence on the drug-release profile. The direct compression method provides tablets with the fastest drug-release profile, followed by the dry-granulation and wet-granulation methods. The particle size of granules and porosity of tablets play an important role, contributing to differences in drug-release profiles.