Electronic Theses and Dissertations

Date of Award

5-1-2026

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

First Advisor

Mohammed Maniruzzaman

Second Advisor

Walter Chambliss

Third Advisor

Eman Ashour

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and motor fluctuations requiring rapid-acting rescue therapy. Apomorphine hydrochloride is an effective on-demand treatment for “OFF” episodes; however, currently available dosage forms have limitations including invasiveness or lack of dose flexibility. This study aimed to design and optimize personalized sublingual films of apomorphine hydrochloride using semisolid extrusion (SSE)-based three-dimensional (3D) printing to achieve rapid drug release and improved patient compliance.

Initially, various polymers were screened for printability, and then based on these findings, formulations loaded with apomorphine hydrochloride were further tested with blends of HPMC K4M and sodium alginate polymers. Drug-loaded formulations (F1–F3) were printed using 15% and 100% infill densities to evaluate the effect of internal structure on drug release and mechanical properties. The films were characterized for dimensional accuracy, weight variation, drug content, disintegration time, in vitro dissolution, tensile strength, folding endurance, and physicochemical compatibility using DSC, FTIR, and SEM analysis.

All printed films (30 × 30 mm²) demonstrated uniform dimensions, minimal weight variation, and drug content ranging from approximately 97% to 99%, indicating consistent drug distribution. The unit dose varied with infill density, where films printed with 15% infill were designed to deliver 10 mg of drug, while those with 100% infill delivered 20 mg, enabling dose modulation within the same film dimensions. These doses are comparable to commercially available sublingual film strengths (10-30 mg), supporting their potential clinical applicability. Thermal and spectroscopic studies confirmed compatibility between the drug and excipients, while SEM images revealed uniform drug dispersion within the polymer matrix. Films printed with 15% infill density showed faster disintegration and drug release due to their porous structure. Among all formulations, F3 with 15% infill exhibited the fastest disintegration (60 sec) and achieved approximately 86% drug release within 10 minutes, whereas F1 with 100% infill showed slower release. Folding endurance values above 200 indicated adequate flexibility for handling.

Overall, SSE-based 3D printing successfully produced personalized sublingual films with tunable drug release by adjusting polymer concentration and infill density. The lead formulation (F3-15% infill) demonstrated rapid disintegration, immediate drug release, and suitable mechanical properties, highlighting the potential of 3D-printed sublingual films as a personalized therapeutic approach for managing Parkinson’s disease “OFF” episodes. Further Ex vivo permeation studies will assess the permeability profile of 3D printed sublingual films.

Available for download on Wednesday, August 02, 2028

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