Electronic Theses and Dissertations

Date of Award

1-1-2023

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

First Advisor

Michael A. Repka

Second Advisor

Dr. Walter Chambliss

Third Advisor

Eman Ashour

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Estrogen Hormonal Replacement Therapy is the most common and most effective means for post-menopausal women to get relief from vasomotor symptoms. Oral films are feasible approaches to designing a dosage form that can include the benefits of oral delivery but circumvent the side effects and risks associated with first-pass metabolism and transdermal delivery. The film releases the drug when it comes in contact with water leaving behind a gel.

In this study, different grades of Hydroxy propyl cellulose (HPC-M, HPC-SL, HPC-SSL) were used as film-forming polymers; propylene glycol was used as a plasticizer, Citric Acid as saliva stimulating agent, Mannitol as a sweetener. Estradiol was dissolved in Ethanol containing propylene glycol, mixed with an aqueous solution of HPC polymer and other excipients, cast and dried, and cut into the desired size of 1cm x 1cm containing a target dose of 1 mg per square centimeter of film. The films were then screened based on their physical-chemical characteristics, weight uniformity, and in-vitro disintegration times; and then further characterized by their surface pH, thickness, content uniformity, folding endurance, in-vitro dissolution, DSC, and FTIR.

The DSC thermograms showed an endothermic melting peak for Estradiol at 178.5 °C. The height of the endothermic peak was reduced in the film formulations. The reduced peak height indicates the partial conversion from crystalline to amorphous state of Estradiol in the polymeric carrier. Two formulations, F4 and F5, were selected for characterization studies based on their disintegration times and physical appearance. In vitro dissolution profiles showed that both formulations had similar release profiles. At the 20-minute mark, F4 (25%w/v polymer) released approximately 77% of the drug, while F5 (30% w/v polymer) had a release of 74%.

The results demonstrated that an oral thin film of Estradiol could be a promising platform for delivering Estradiol through the buccal mucosa to treat menopausal symptoms.

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