In the search for a novel water-soluble general anesthetic agent the activity of an alpha-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice, good in vitro activity at GABA(A) receptors was also conferred. Within the series of compounds good enantioselectivity for both in vitro and in vivo activity was found, supporting a protein-mediated mechanism of action for anesthesia involving allosteric modulation of GABA(A) receptors. alpha-Amino acid phenolic ester 19, as the hydrobromide salt Org 25435, was selected for clinical evaluation since it retained the best overall anesthetic profile coupled with improved stability and water solubility. In the clinic it proved to be an effective intravenous anesthetic in man with rapid onset of and recovery from anesthesia at doses of 3 and 4 mg/kg.

No abstract

Floating tablets of Cefuroxime Axetil were prepared using Albizia gum, Dammar gum and Moi gum as polymers for controlling the drug release. Cefuroxime Axetil is a poorly water-soluble drug (second-generation cephalosporin) and its bioavailability is very low. The rate of absorption and the extent of bioavailability for such insoluble drug are controlled by the rate of dissolution in the gastrointestinal fluids. Two types of diluents were used and the drug release was compared. Pure drug and optimized formulation were subjected to the drug excipient compatibility studies using FTIR and DSC. The studies revealed that there was no interaction between the drug and excipients. In order to increase the drug release, channeling agents were introduced namely Lactose and DCP. Lactose is water soluble diluent and DCP is water insoluble diluent. All the formulations were taken and studied for the precompression parameters and found that they were within the limits. Precompression parameters were performed to all the formulations and were found to be in the acceptable limit which ensures the good flow properties. Formulation F4CADL containing gum dammar and lactose as channeling agent showed good results when compared with other formulations. The floating lag time of the optimized formulation was very short and the percentage of drug release at the end of 12 hours was found to be high. The drug release kinetics revealed that F4CADL follows Korsmeyer-Peppas and the mechanism was non-fickian diffusion. Optimized formulation was selected for in vivo studies by using albino rabbits. It was found that the tmax was extended for prolonged period of time.

No abstract

No abstract