1: J Control Release. 2005 Feb 16;102(3):657-68. 

Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly
water-soluble drugs: a case study with risperidone.

Ould-Ouali L, Noppe M, Langlois X, Willems B, Te Riele P, Timmerman P, Brewster
ME, Arien A, Preat V.

Universite Catholique de Louvain, Department of Pharmaceutical Technology,
Avenue Mounier, 73 UCL 7320, 1200 Brussels, Belgium.

Diblock PEG-p(CL-co-TMC) [methoxypoly(ethylene
glycol)-poly(caprolactone/trimethylene carbonate)] copolymers form micelles
spontaneously and significantly increase the solubility of poorly water-soluble
drugs. The aim of this work was to assess these diblock copolymers as oral drug
delivery systems in both in vitro and in vivo experiments using risperidone as a
model drug. The permeation of risperidone through Caco-2 cell monolayers showed
that the apparent permeation coefficient (Papp) was slightly reduced when
risperidone was formulated with the copolymer. Based on the higher apparent drug
solubility, the copolymer increased drug flux or the total amount of drug which
crossed the Caco-2 monolayers. The Papp of the micelle formulation was higher at
37 degrees C than at 4 degrees C. After oral administration to rats, the
pharmacokinetic parameters and the pharmacological effect were evaluated. Time
courses of receptor occupancy by risperidone after oral administration were
similar when risperidone was encapsulated in PEG-p(CL-co-TMC) micelles or
solubilized in an aqueous tartaric acid vehicle. The areas under the curve (AUC)
were not significantly different although the maximal concentration (Cmax) was
twofold lower with the copolymer. The polymeric micelles of PEG-p(CL-co-TMC)
seem to be a good candidate for oral drug delivery of poorly soluble drugs.

PMID: 15681087 [PubMed - in process]