Clonazepam release from bioerodible hydrogels based on semi-interpenetrating polymer networks composed of poly(epsilon-caprolactone) and poly(ethylene glycol) macromer

Int J Pharm. 1999 Apr 30;181(2):235-42. doi: 10.1016/s0378-5173(99)00031-9.

Abstract

Poly(ethylene glycol)(PEG) macromers terminated with acrylate groups and semi-interpenetrating polymer networks (SIPNs) composed of poly(epsilon-caprolactone)(PCL) and PEG macromer were synthesized to obtain a bioerodible hydrogel. Polymerization of PEG macromer resulted in the formation of cross-linked gels due to the multifunctionality of macromer. Glass transition temperature (Tg) and melting temperature (Tm) of PEG networks and PCL in the SIPNs were inner-shifted, indicating an interpenetration of PCL and PEG chains. Water content in the SIPNs increased with increasing PEG weight fraction due to the hydrophilicity of PEG. The amount of clonazepam (CNZ) released from the SIPNs increased with higher content in the SIPNs, lower drug loading, lower concentration of PEG macromer during the SIPNs preparation, and higher molecular weight of PEG. In particular, a combination with low PEG content and low CNZ solubility in water led to long-term constant release from these matrices in vitro and in vivo.

MeSH terms

  • Animals
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacokinetics*
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacokinetics*
  • Biodegradation, Environmental
  • Calorimetry, Differential Scanning
  • Clonazepam / administration & dosage
  • Clonazepam / chemistry
  • Clonazepam / pharmacokinetics*
  • Drug Implants
  • Gels
  • Male
  • Polyesters / administration & dosage
  • Polyesters / chemistry
  • Polyesters / pharmacokinetics*
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics*
  • Rabbits

Substances

  • Anticonvulsants
  • Biocompatible Materials
  • Drug Implants
  • Gels
  • Polyesters
  • polycaprolactone
  • Polyethylene Glycols
  • Clonazepam