PLGA nanoparticles prepared by nanoprecipitation: drug loading and releasestudies of a water soluble drug

The nanoprecipitation technique for preparation of nanoparticles suffers th e drawback of poor incorporation of water soluble drugs. The aim of this st udy was therefore to assess various formulation parameters to enhance the i ncorporation of a water soluble drug (procaine hydrochloride) into poly(DL- lactide-co-glycolide) (PLGA) nanoparticles prepared by this technique. Appr oaches investigated for drug incorporation efficiency enhancement included the influence of aqueous phase pH, replacement of procaine hydrochloride wi th procaine dihydrate and the inclusion of excipients: poly(DL-lactide) (PL A) oligomers, poly(methyl methacrylate-co-methacrylic acid) (PMMA-MA) or fa tty acids into the formulation. The nanoparticles produced were submicron s ize (<210 nm) and of low polydispersity. It was found that an aqueous phase pH of 9.3, replacement of procaine hydrochloride with procaine dihydrate a nd the incorporation of PMMA-MA, lauric and caprylic acid into the formulat ion could enhance drug incorporation efficiency without the size, morpholog y and nanoparticle recovery being adversely influenced. For instance changi ng the aqueous phase pH from 5.8 to 9.3 increased nanoparticle recovery fro m 65.1 to 93.4%, drug content from 0.3 to 1.3% w/w and drug entrapment from 11.0 to 58.2%. However, the presence of high ratios of lauric acid and pro caine dihydrate in the formulation adversely affected the morphology and si ze of the nanoparticles. Also, PLA oligomers were not considered a feasible approach since it decreased drug entrapment from 11.0 to 8.4% and nanopart icle recovery from 65.1 to 19.6%. Drug release from nanoparticles appears t o consist of two components with an initial rapid release followed by a slo wer exponential stage. This study has demonstrated that formulation variabl es can be exploited in order to enhance the incorporation of a water solubl e drug into PLGA nanoparticles by the nanoprecipitation technique. (C) 1999 Elsevier Science B.V. Al rights reserved.