Electronic Theses and Dissertations

Date of Award

8-1-2022

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Michael A. Repka

Second Advisor

Michael A. Repka

Third Advisor

Eman A. Ashour

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Drug delivery systems are evolving as pharmaceutical excipients and the manufacturing technologies evolve. Recently, 3D printing was introduced as a promising and versatile manufacturing technology of solid dosage forms from liquid, semi-solid, and solid intermediates. This work presents two examples of employing hot melt extrusion and fused deposition 3D printing technology to fabricate bioadhesive delivery systems loaded with miconazole. The first project shows a successful fabrication of four intraoral mucoadhesive film formulations, the formulations consist of different ratios of Eudragit RS, Hydroxypropyl cellulose EF (HPC EF), and Hypromellose HME 15LV. After the HME and 3DP fabrication of the films, the API’s solid state was characterized in all 3DP films using DSC, where it has been indicated that miconazole had transformed from crystalline to amorphous. Additionally, the drug content analysis via HPLC revealed that the miconazole content was within the acceptance limits, ranging from 93% in F1 to 102% in F3. The drug release profile indicates an extended release was realized over 12 hrs period. Furthermore, the 3DP films showed a superior adhesion properties as well as mechanical endurance. In the second project, the goal was to fabricate modified release bioadhesive vaginal film loaded with miconazole to treat vulvovaginal candidiasis. Four formulations were developed, where HPC EF was used as filler and bioadhesive agent in combination with three different release retardants to alter the release profile, the release retarding agents are Polycaprolactone 45,000 (PCL 45K), Eudragit RLPO, and HPMC HME. All formulations were fabricated successfully as cylindrical films. Using HPLC the drug content was observed to be close to 100% of the theoretical content except in the formulation containing PCL 45K the content was 89%. The drug release studies revealed that all formulations were capable to extend the miconazole release over 24 hrs in the vaginal simulating fluid. The physical state of miconazole in the formulations was investigated using DSC and confirmed by the scanning electron microscope (SEM), it was evident that miconazole has transformed from crystalline to amorphous, forming a solid dispersion. Furthermore, it was proven via an ex vivo mucoadhesion study that the fabricated films possess sufficient mucoadhesive properties.

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