Electronic Theses and Dissertations

Date of Award

1-1-2021

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Michael A. Repka

Second Advisor

Soumyajit Majumdar

Third Advisor

Samir Ross

Relational Format

dissertation/thesis

Abstract

Hot-melt extrusion (HME), an adaptable technology, has established its position in manufacturing operations like amorphous solid dispersions, immediate and controlled oral formulations, implants and taste masked products. In recent years the industrial focus has shifted towards continuous manufacturing, thus HME is being explored for new applications. The aim of this research was to investigate the novel applications of HME by carrying out an in-depth study to understand the interaction between the process and product and to investigate a screening tool for its small-scale formulation and development.As HME consumes large amount of samples during the developmental phase, we investigated a screening tool by using minimum quantity of active pharmaceutical ingredient. Vacuum Compression Molding (VCM) is a fusion based method to form solid specimens starting from powders. Mixtures of indomethacin with drug carriers were processed using VCM and HME. Thermal characterization such as differential scanning calorimetry and powder x-ray diffraction along with dissolution studies were performed to prove the effectiveness of VCM as a screening tool for HME based formulations at small scale.

The conventional techniques used for the preparation of nanostructured lipid carriers (NLC) are multi-step and time-consuming batch processes with low productivity. Hence, the continuous manufacturing advantage of HME was investigated for the preparation of NLC along with its process variation impact on the formulation composition. After optimization of screw configuration and process parameters, these formulations were successfully prepared using HME in a continuous manner. In addition, the itraconazole NLCs were explored for the pulmonary drug delivery by characterizing its aerodynamic properties thereby showing promising results for pulmonary aspergillosis treatment.

To overcome the disadvantages associated with conventional liquid self-micro emulsifying drug delivery systems (SMEDDS), solid SMEDDS were formulated using HME. Solid surfactants were used to emulsify the lipids in the formulation. The prepared solid SMEDDS were characterized for globule size, PDI, zeta potential, dissolution test and differential scanning calorimetry. HME has gained attention in the pharmaceutical industry but its potential in preparing solid SMEDDS is still unexplored. Hence, solid SMEDDS were manufactured using HME for the first time.

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