A new engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery

Panita Maturavongsadit; Gayane Paravyan; Martina Kovarova; J Victor Garcia; S Rahima Benhabbour

doi:10.1016/j.ijpx.2020.100068

A new engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery

Int J Pharm X. 2020 Dec 25:3:100068. doi: 10.1016/j.ijpx.2020.100068. eCollection 2021 Dec.

Authors

Panita Maturavongsadit¹, Gayane Paravyan¹, Martina Kovarova^{2

3}, J Victor Garcia^{2

3}, S Rahima Benhabbour^{1

4}

Affiliations

¹ Joint Department of Biomedical Engineering, North Carolina State University and The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² International Center for the Advancement of Translational Science, USA.
³ Division of Infectious Diseases, Center for Aids Research, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Abstract

We present a long-acting (LA) biodegradable polymeric solid implant (PSI) fabricated using a new process combining in-situ phase inversion and compression. This robust process allows fabrication of solid implants that can have different shapes and sizes, accommodate high drug payloads, and provide sustained drug release over several months. Herein the integrase inhibitor dolutegravir (DTG) was used to develop PSIs for HIV prevention. PSIs were fabricated using a three-step process by (a) phase inversion of DTG-loaded polymer solution to form an initial in-situ forming implant in an aqueous solution, (b) micronization of dried DTG-loaded solid implants, and (c) compression of the micronized DTG-loaded solid implants to form the PSI. High drug loading (up to 85 wt%) was achieved in the PSIs. DTG exhibited minimum burst release in the first 24 h (<6%) and sustained release kinetics over 6 months. The release kinetics of DTG can be fine-tuned by varying drug-loading concentration, the ratio of polymer (poly(lactic-co-glycolic acid), PLGA) to solvent (N-methyl-2-pyrrolidone, NMP) and polymer (PLGA) molecular weight in the precursor solution. The physical/chemical properties of DTG were retained post-storage under accelerated storage conditions (40 °C/75% relative humidity) for 6 months. The versatility of this technology makes it an attractive drug delivery platform for HIV prevention applications.

Keywords: Compression; HIV prevention; In-situ; Long-acting drug delivery; Phase inversion; Poly(lactic-co-glycolic acid); Solid implants.

Abstract

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