Design and Process Considerations for Preparation of Modified Release Ivermectin and Praziquantel Tablets by Wet Granulation

Abstract

Dosage forms containing Ivermectin (IVER) and Praziquantel (PRAZ) are important combination drug products in animal health. Understanding the relationship between products with differing in vitro release characteristics and bioequivalence could facilitate generics. The goal of this study was to create granulations for each active ingredient, with similar release mechanisms, but substantially different in vitro release rates, and then compressing these granulations into tablets with differing release rates. Four granulation formulations were created: fast and modified release for PRAZ and IVER, respectively. The manufacturing process used high shear wet granulation and fluid bed drying, milling and sieving. Solid components, including the granulating agent, were blended in a high shear granulator and then water or a hydroalcoholic solution was added to activate the binder and initiate granule formation. Drying in a fluid bed with inlet air temperature set for 70°C and inlet air volume adjusted as required to maintain fluidization. Milling was performed in a cone mill and classification of final product was done using a vibratory sieve shaker with 18, 20, 40, and 60 mesh sieves. Formulations and processing approaches were successfully developed to produce a collection of PRAZ and IVER granules with differing particle size distributions and in vitro release characteristics. Differences in drug content in the classified granulations were observed and attributed to the low surface energy of PRAZ and the different approaches used to incorporate the active ingredients. The granulations were compressed via compaction simulator and the results show the monolithic tablets had four different release profiles.

Graphical Abstract