Text

theses

Wet granulation is the process of particle size enlargement by inducing agglomeration of individual particles by addition of a liquid binding agent. Granulation is an integral step during pharmaceutical manufacturing for solid doses, which is usually followed by unit operations such as drying, milling and finally tableting and coating. This process can be performed in both batch and continuous forms. Granulation process is typically known to alleviate problems of powder handling, non-uniform distribution of active pharmaceutical ingredients (API), segregation and poor flow properties of powders/blends. However, as pharmaceutical manufacturing is evolving to include Quality by Design (QbD), numerous opportunities of research in the areas of continuous manufacturing and Process Analytical Technology (PAT) are now being explored, allowing for improvement in existing batch manufacturing and in continuous manufacturing. The objective of the thesis is to study the effect of process conditions employed during granulation on the final quality attributes of tablets prepared. For this study tablets were prepared by granules produced in a high-shear batch granulator (HSG) and a continuous twin screw granulator (TSG) with the aim of comparing the robustness of the two processes and quality attributes of tablets for a broad range of operating conditions. A four component low-dose formulation with Caffeine as API was selected for the purpose of the study. The formulation consisting of 44% (w/w) MCC Avicel PH101, 44% (w/w) monohydrate a-lactose, 8% (w/w) Caffeine as the API and 4% (w/w) Polyvinylpyrrolidone was pre-blended and used for granulation experiments. In this dissertation, parameters such as liquid-solid (L/S) ratio, wet-massing time and chopper speed were varied to produce granules in a face-centered DoE augmented with 3 center points. Granules produced were analyzed for granule size distribution, porosity, aspect ratio and Hausner ratio. Characterization of the twin-screw granulator was carried out by setting up a d-optimal DoE with operational parameters; namely, (L/S) ratio, feeder throughput, screw RPM, granulator barrel temperature, and screw configuration variations. The design space was optimized by the size distribution of the granules and torque to determine the most significant parameters. Granules produced from both equipment were used to make flat-faced tablets. The robustness of the two granulation processes were compared by critical attributes such as granule size distribution, porosity, tablet hardness, tablet dissolution profiles, content uniformity of the active ingredient and the optimum operation design spaces of the processes.

ETD_8002

M.S.

Includes bibliographical references

by Kallakuri Suparna Rao

doi:10.7282/T3319ZSP

ETD graduate

The author owns the copyright to this work.