Electronic Theses and Dissertations

Date of Award

2019

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Pharmaceutics and Drug Delivery

First Advisor

Michael A. Repka

Second Advisor

Eman Ashour

Third Advisor

Soumyajit Majumdar

Relational Format

dissertation/thesis

Abstract

The objective of the current study was to investigate the feasibility of Theophylline and Nicotinamide pharmaceutical co-crystals by hot melt extrusion technology and to evaluate the processability by using HPMCAS-MG and PEO as polymer carriers. Theophylline, a BCS class I was chosen as a model drug and Nicotinamide, a vitamin B family was selected as a suitable co-former for the co-crystals study. HPMCAS-MG, a synthetic polymer and PEO, water-soluble polymer were chosen as polymer carriers for the study. To optimize the process parameters and formulations, a physical mixture of 1:1 molar ratio of theophylline and nicotinamide were prepared. Physical mixture was extruded through the co-rotating twin-screw extruder (11mm Process 11, Thermo Fisher Scientific) utilizing a modified screw configuration. The extrusion was performed at different temperatures and screw speeds. The temperatures used for the experiment were 140C, 150C, 160C and 170C along with a screw speed of 50 rpm. The presence of mixing and temperature were found to be the critical parameters that influence the formation of co-crystals during extrusion processing. The solid state of the samples was analyzed by Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and X-ray powder diffractometry (PXRD). A Scanning electron microscopy (SEM) was conducted to study the morphology of the extrudates. The in vitro drug release study was performed and the results indicate that the co-crystals exhibited a relatively high drug release in 5mins when compared to the pure theophylline and the co-crystals with PEO as carrier shobetter dissolution profile when compared to the one with HPMCAS-MG as carrier. The co-crystals were stable for three months at accelerated stability conditions of 40 (±2) C and 75 (±5) % RH.

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