Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion

Drug Dev Ind Pharm. 2011 Jun;37(6):694-701. doi: 10.3109/03639045.2010.535822. Epub 2011 Jan 13.

Abstract

The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Drug Carriers / chemistry
  • Drug Stability
  • Drug Storage
  • Hot Temperature
  • Male
  • Methacrylates / chemistry*
  • Methylmethacrylates
  • Polyethylene Glycols / chemistry*
  • Povidone / chemistry*
  • Rats
  • Rats, Wistar
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Solubility

Substances

  • Drug Carriers
  • Methacrylates
  • Methylmethacrylates
  • Receptor, Cannabinoid, CB1
  • Eudragit-E
  • Polyethylene Glycols
  • Povidone