Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol

Abstract

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188)on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength andbioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study ofibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility ofibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above theratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutionswith the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5-and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamergel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml.Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, mentholdid the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen(15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2 mg/ml was administered easily to the anus and to remain at the administeredsite without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations,Cmaxand AUC of ibuprofen thandid solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquidsuppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhancethe rectal bioavailability of ibuprofen.© 2004 Elsevier B.V. All rights reserved.