ABSTRACT
The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.
Subject(s)
Animals , Dogs , Female , Male , Area Under Curve , Delayed-Action Preparations , Drug Compounding , Methods , Drug Delivery Systems , Drug Design , Expert Systems , Glipizide , Chemistry , Pharmacokinetics , Hypoglycemic Agents , Chemistry , Pharmacokinetics , Neural Networks, Computer , Osmosis , Polyethylene Glycols , Chemistry , Random Allocation , Sodium Chloride , Chemistry , Solubility , TabletsABSTRACT
To compare the molecular characteristics of the Capsid gene and 3' untranslation region (3'UTR) of Getah viruses (GETV) isolated in Hainan Province and Hebei Province of China,the viral RNAs were extracted from M1(Hainan), HB0215-3 and HB0234(Hebei) virus stocks. Capsid gene segments and 3' UTR segments from three strains of Chinese GETV were obtained by RT-PCR and then sequenced. The obtained nucleotide sequences were analyzed using the Clustal X(1.8), DNASTAR, MAGA3.1 programs. The full-length Capsid gene of the 3 strains of Chinese GETV were comprised of 801, 804 and 804 nucleotides each, encoding the protein of 267,268 and 268 amino acids each. Sequencing of Capsid gene fragments showed that two strains of Hebei isolates were identical and had homology of 97.6% at nucleotide level and 97.8% at amino acids level with M1. Their homologies when compared with strains isolated from other countries were also high at nucleotide levels (95.4%-99.6%). The 3'UTR from the three strains were comprised of 411, 401 and 401 nucleotides each, and had found specific deletion of 10 nt at position 44-54 and two specific nucleotide sites that was T at position 64 and C at position 148. GETV isolated in China presented relation of the year of virus isolation with the phylogenesis distance when compared with the other GETV strains and comprised a genetically highly conserved group.