PLGAs from PolySciTech used in development of periodontal-simulating test chamber for drug release assays

PLGA microparticles are routinely used for delivery of long-acting injectable drugs. For these formulations, the drug is encapsulated in the biodegradable PLGA and elutes out slowly due to drug diffusion and polymer degradation. A rather critical question is at what rate the drug elutes out and this depends on the formulation parameters and polymer type used. In order to test this, however, a system must be designed which replicates the important components of the human body and allows for the drug elution to be measured using HPLC or other analytical techniques. Arestin is a unique formulation in that it is designed to go into the periodontal pocket (gumline) around teeth and slowly release antibacterial agents for localized activity. Due to the location of this formulation (as opposed to typical intra-muscular injection sites in the shoulder or buttocks used for conventional LAR formulations) it has a rather unique local environment in the gumline which is difficult to replicate. Recently, researchers at University of Pittsburgh, Magee-Women’s Research Institute, Qrono Inc, and Food and Drug Administration used multiple PLGAs (AP125, AP037, AP081, AP030, AP150) purchased from PolySciTech (www.polyscitech.com) to develop a variety of PLGA-minocycline formulations and test these out on a novel flow-release chamber used to represent the periodontal pocket release. This research holds promise to improve analytical techniques applied for testing long-acting injectable formulations. Read more: Patel, Sravan Kumar, Ashlee C. Greene, Stuti M. Desai, Sam Rothstein, Iman Taj Basha, James Scott MacPherson, Yan Wang et al. "Biorelevant and screening dissolution methods for minocycline hydrochloride microspheres intended for periodontal administration." International Journal of Pharmaceutics 596 (2021): 120261. https://www.sciencedirect.com/science/article/pii/S037851732100065X

“Abstract: Currently, there is no compendial-level method to assess dissolution of particulate systems administered in the periodontal pocket. This work seeks to develop dissolution methods for extended release poly(lactic-co-glycolic acid) (PLGA) microspheres applied in the periodontal pocket. Arestin®, PLGA microspheres containing minocycline hydrochloride (MIN), is indicated for reduction of pocket depth in adult periodontitis. Utilizing Arestin® as a model product, two dissolution methods were developed: a dialysis set-up using USP apparatus 4 and a novel apparatus fabricated to simulate in vivo environment of the periodontal pocket. In the biorelevant method, the microspheres were dispersed in 250 μL of simulated gingival crevicular fluid (sGCF) which was enclosed in a custom-made dialysis enclosure. sGCF was continuously delivered to the device at a biorelevant flow rate and was collected daily for drug content analysis using UPLC. Both methods could discriminate release characteristics of a panel of MIN-loaded PLGA microspheres that differed in composition and process conditions. A mechanistic model was developed, which satisfactorily explained the release profiles observed using both dissolution methods. The developed methods may have the potential to be used as routine quality control tools to ensure batch-to-batch consistency and to support evaluation of bioequivalence for periodontal microspheres. Keywords: Dissolution PLGA Minocycline Biorelevant Microspheres Periodontal Modeling”