Drug Discov Ther. 2021;15(1):20-27. (DOI: 10.5582/ddt.2021.01004)

Dry fabrication of poly(dl-lactide-co-glycolide) microspheres incorporating a medium molecular drug by a ball mill method

Matsumoto A, Murakami M


Poly(dl-lactide-co-glycolide) acid (PLGA) microspheres is a useful carrier for controlled drug release. However, the organic solvents used in their conventional manufacturing process may affect the chemical structure of a macromolecular drug. Thus, we investigated the applicability of a dry fabrication method for PLGA microspheres. Cyanocobalamin (MW = 1,355) (VB12) was used as a model drug, and it formed agglomerates under mild conditions with powdered PLGA in a generic ball milling system. Light and scanning electron microscopy showed the formation of PLGA microspheres and few agglomerates. The obtained microspheres had the particle size injectable as suspensions, namely smaller than 150 μm specified for subcutaneous and intramuscular injections by the Japanese Pharmacopoeia. The observed and theoretical drug contents were consistent. PLGA microspheres fabricated using a combination of small (ϕ3 mm) and large (ϕ10 mm) balls showed low initial burst of cyanocobalamin release in vitro. The in vitro drug release profile was equivalent with that of the microspheres fabricated by a conventional oil-in-water emulsion solvent evaporation method, while the drug release profile was influenced by the brand of the PLGA used. To prevent drug loss during fabrication, the dry fabrication method using a ball mill should be applied to prepare PLGA microspheres containing a medium macromolecular drug.

KEYWORDS: biodegradable polymer, microspheres, solvent-free, long-acting injectable formulation, mechanical alloying

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