Desai, Stuti M
(2019)
Development of Biorelevant In Vitro Release Testing Methods for Periodontal Microparticles.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Dissolution testing is one of the primary methods employed not only as a quality control tool but also to evaluate bioequivalence and assess the effect of process and formulation parameters on drug release. Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. Therefore, the goal of this work is to develop and demonstrate the utility of dissolution methods for microparticles applied in the periodontal pocket. Arestin®, a clinically used extended release periodontal system was used as the reference product. It is composed of poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with an antibacterial drug, minocycline hydrochloride (MIN). Two methods were evaluated in this study. The first method utilized a standard USP IV apparatus modified to include a dialysis tube with dispersed microparticles, which was developed as a rapid screening method. In the second method, a novel apparatus was designed by our group to simulate the in vivo environment of the periodontal pocket. The applicability of these methods was evaluated by rigorously testing for reproducibility and discriminatory ability. To test the discriminatory ability of the developed methods, a panel of MIN-loaded PLGA microparticles that differed in composition and process conditions were utilized. The method utilizing the USP IV apparatus was equipped with online UV-analysis and was carried out at a flow rate of 10mL/min for 3 days. Microparticles that showed different dissolution profiles in this method were tested in the novel, more biorelevant small volume apparatus, which was designed to hold 250µL of gingival crevicular fluid simulant (sGCF), where the particles are dispersed. sGCF was continuously delivered to the device at a biorelevant flow rate and collected daily for dug content analysis using a stability-indicating UPLC method. Both the developed methods could discriminate between Arestin® and the comparators. Release of MIN was largely dependent on molecular weight of PLGA used, with higher molecular weight showing higher release. The methods evaluated in this work can be used in routine quality control analysis to detect batch-to-batch variability. Future studies can evaluate the applicability of the developed methods to assess bioequivalence of MIN-loaded periodontal systems.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
9 April 2019 |
| Date Type: |
Publication |
| Defense Date: |
21 March 2019 |
| Approval Date: |
9 April 2019 |
| Submission Date: |
9 April 2019 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
126 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Dissolution testing, microparticles, biorelevant, small volume, minocycline, PLGA, USP IV |
| Date Deposited: |
09 Apr 2019 15:54 |
| Last Modified: |
09 Apr 2021 05:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/36408 |
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