Effects of manufacturing process variables on in vitro dissolution characteristics of extended-release tablets...

The purpose of this study was to investigate the effect of three process variables: distribution of hydroxypropyl methylcellulose (HPMC) within the tablet matrix, amount of water for granulation, and tablet hardness on drug release from the hydrophilic matrix tablets. Tablets were made both by direct compression as well as wet granulation method. Three formulations were made by wet granulation, all three having the exact same composition but differing in intragranular:intergranular HPMC distribution in the matrix. Further, each formulation was made using two different amounts of water for granulation. All tablets were then compressed at two hardness levels. Dissolution studies were performed on all tablets using USP dissolution apparatus I (basket). The dissolution parameters obtained were statistically analyzed using a multilevel factorial-design approach to study the influence of the various process variables on drug release from the tablets. Results indicated that a change in the manufacturing process could yield significantly dissimilar dissolution profiles for the same formulation, especially at low-hardness level. Overgranulation could lead to tablets showing hardness-dependent drug-release characteristics. Studies showed that intergranular addition of a partial amount of HPMC (i.e., HPMC addition outside of granules) provided a significant advantage in making the formulation more robust over intragranular addition (i.e., that in which the entire amount of HPMC was added to the granules). Dissolution profiles obtained for these tablets were relatively less dependent on tablet hardness irrespective of the amount of water added during granulation.