Impact of microparticle formulation approaches on drug burst release: a level A IVIVC

J Microencapsul. 2014;31(7):674-84. doi: 10.3109/02652048.2014.913724. Epub 2014 Jun 25.

Abstract

Aim: To study the effect of poly(d,l-lactic-co-glycolic acid) (PLGA) microparticles (MPs) preparation techniques on particle physical characterization with special emphasis on burst drug release.

Methods: A basic drug clozapine was used in combination with acid-terminated PLGA. Two approaches for MP preparation were compared; the in situ forming microparticle (ISM) and the emulsion-solvent evaporation (ESE) methods using an experimental design. The MPs obtained were compared according to their physical characterization, burst release and T80%. An in vivo pharmacokinetic study with in vitro-in vivo correlation (IVIVC) was also performed for the selected formula.

Results: Both methods were able to sustain drug release for three weeks. ISM produced more porous particles and was not effective as ESE for controlling burst release. A good IVIVC (R(2) = 0.9755) was attained when injecting the selected formula into rats.

Conclusion: MPs prepared with ESE showed a minimum burst release and a level A IVIVC was obtained when administered to rats.

Keywords: Burst release; IVIVC; factorial design; in situ forming microparticles; polymer Tg; uncapped PLGA.

MeSH terms

  • Animals
  • Antipsychotic Agents* / chemistry
  • Antipsychotic Agents* / pharmacokinetics
  • Antipsychotic Agents* / pharmacology
  • Clozapine* / chemistry
  • Clozapine* / pharmacokinetics
  • Clozapine* / pharmacology
  • Delayed-Action Preparations
  • Lactic Acid* / chemistry
  • Lactic Acid* / pharmacokinetics
  • Lactic Acid* / pharmacology
  • Male
  • Polyglycolic Acid* / chemistry
  • Polyglycolic Acid* / pharmacokinetics
  • Polyglycolic Acid* / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats

Substances

  • Antipsychotic Agents
  • Delayed-Action Preparations
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Clozapine