| Lacking of efficient medication, cerebritis caused by herpes simplex virus infection - accounting for 10-20% cases of the overall cerbritis - still has been a vital investigation subject in the CNS virus-infected diseases. Though having been proved an efficient drug for herpes simplex virus, penciclovir (PCV) showed less antivirus effect in the CNS owing to its low concentration in the CNS. As polyoxyethylene castor oil was proved increasing the permeability of blood brain barrier, microemulsions comprised of polyoxyethylene castor oil (Cremophor EL) were designed as carrier to discuss the feasibility of enhancing PCV distribution in the brain. In this paper, formulation and preparation, microemulsion structure, physicochemical, diluted characters, solubilizing mechanisms, in vitro release, acute toxicity, tissue distribution and pharmacyokinetics of Cremophor EL microemulsions were investigated.Solubilities of PCV in different solvents including surfactant, cosurfactant, oils and aqueous phases were determined in order to obtain optimized components of microemulsions. All surfactants showed medium solubilizing abilities and cosolvents such as PEG 400-water (1:1), propylene glycol-water(1:1), markedly increased solubility of PCV. The partition coefficient of PCV in PBS (pH 7.4) and octanol (log P) was -2.015.Surfactant systems were optimized by pseudoternary phase diagram via valuing microemulsion region area (AMR) and Maxmum oil concentration solubilized by 30% of the total surfactants(MAO30). Combined use of lecithin and hydrophilic surfactants for mixed surfactants markedly enlarged AMR. Thereinto, AMR was manifested maximum for combining lecithin with...
|
PDF Full Text Request