The Influence Of Screw Configuration And Other Mechanistic Approaches On The Morphology And Release Of Drugs From Polymeric Matrices Utilizing Hot-Melt Extrusion Technology
Twin-screw extrusion, often referred to as Hot-Melt Extrusion within the pharmaceutical industry, is an efficient, continuous and solvent-free process that has been investigated extensively for its solubility enhancement applications, and, to a lesser degree, for its potential to replace more conventional “batch” technologies. The research contained herein focuses on the latter of these with attention paid to the effects of screw configuration. In this research, the twin-screw extrusion process was utilized to produce taste masked formulations of a BCS I API, which necessitated the prevention of amorphous phase formation. The resulting granules were subsequently incorporated into an immediate release orally disintegrating tablet (ODT) platform. This processing technology was also evaluated as an alternative platform for the production of dry granulations, henceforth referred to as Twin-Screw Dry Granulation (TSDG). This novel processing approach was investigated using Quality by Design (QbD) principles; however, as the QbD paradigm in product oriented, the process was assessed by the successful production of a drug intermediate and, ultimately, an optimized target formulation. The TSDG process was utilized to produce a high drug loaded sustained release solid oral dosage form in which the crystalline lattice was preserved. Moreover, as a fundamental purpose of granulating technologies is the improvement of the flowability of one or more of the granule constituents, the resulting granules were assessed for enhanced flowability when compared to the very poorly flowing API. Finally, the effects of screw configuration on API morphology was evaluated for the effects of system dependence as the observed existing literature focuses on single systems wherein the effects of screw configuration on API morphology are not assessed for their variations from one carrier system to another. Moreover, the effects of screw configuration were evaluated from the standpoint of the preservation of the API crystalline lattice as the observed existing information on screw configuration within the pharmaceutical literature focuses on solubility enhancement via conversion of the API crystalline lattice into either a molecularly dispersed solid solution or an amorphous solid dispersion
