Biodegradable polymeric microspheres for nalbuphine prodrug controlled delivery

In vitro characterization and in vivo pharmacokinetic studies

Fang I. Liu, J. H. Kuo, K. C. Sung, Oliver Y.P. Hu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The objective of this work was to study the in vitro characteristics as well as in vivo pharmacokinetic performance of a series nalbuphine (NA) prodrug-loaded microspheres. An oil-in-water solvent evaporation method was used to incorporate the various NA prodrugs into poly(D,L-lactide-co-glycolide) (PLGA)-based microspheres. The morphology of microspheres under the scanning electron microscopy (SEM) revealed a spherical shape with smooth surface. Drug release rates for the microspheres were found to be a function of prodrug hydrophilicity, with higher drug release rates for microspheres loaded with more hydrophilic prodrugs. The release profiles fit well to the Baker and Lonsdale's spherical matrix model, suggesting the drug release from microspheres was consistent with a diffusion mechanism. The in vivo pharmacokinetic studies after s.c. injection of microspheres into rabbits showed sustained plasma NA-time profiles, with approximately 104.7, 67.2, and 41.0% relative bioavailability for microspheres loaded with nalbuphine propionate (NAP), nalbuphine pivalate (NPI), and nalbuphine decanoate (NDE), respectively. The in vitro release characteristics correlated well with the in vivo pharmacokinetic profiles. The results indicated that the prodrug hydrophilicity had significant effects on the in vitro as well as in vivo drug release kinetics. The present study demonstrates the feasibility of using biodegradable polymeric microspheres for controlled delivery of NA prodrugs.

Original languageEnglish
Pages (from-to)23-31
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume257
Issue number1-2
DOIs
Publication statusPublished - May 12 2003
Externally publishedYes

Fingerprint

Nalbuphine
Prodrugs
Microspheres
Pharmacokinetics
Hydrophobic and Hydrophilic Interactions
Decanoates
In Vitro Techniques
Propionates
Feasibility Studies
Electron Scanning Microscopy
Biological Availability
Oils
Rabbits

Keywords

  • Controlled release
  • Microsphere
  • Nalbuphine prodrug
  • Poly(D,L-lactide-co-glycolide)

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Biodegradable polymeric microspheres for nalbuphine prodrug controlled delivery : In vitro characterization and in vivo pharmacokinetic studies. / Liu, Fang I.; Kuo, J. H.; Sung, K. C.; Hu, Oliver Y.P.

In: International Journal of Pharmaceutics, Vol. 257, No. 1-2, 12.05.2003, p. 23-31.

Research output: Contribution to journalArticle

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