Studies On Alfuzosin Hydrochloride Osmotic Pump Tablets

Aflzosin Hydrochloride （AH） is a quinazoline derivatives and wildly used in treatment of Benign prostatic hyperplasia （BPH）.In this paper, micro-porous osmotic pumps （MPOP） were prepared, taking AH as the model drug. Based on the comprehensive pre-formulation research, lactoses were used as osmogents. Cellulose acetate （CA）, dibutylphthalate （DBP） and polyethylene glycol 400 （PEG-400） were selected as the coating materials and acetone-water （95:5） co-solvent was employed as the coating medium.Also, the effects of dosage of osmogents, fillers, coating mediums, DBP, PEG-400 and coating level on the drug release character were investigated. The coating formulation and process were optimized by orthogonal design, having the Similar Factor（f₂） as the evaluation standard.After water penetrated into the core and formed a saturated drug solution, the osmotic pressure induced a rapid expansion of the membrane leading to the formation of pores, through which the drug were released. The effects of coating levels and PEG-400 level on tablets swelling behavior were described.The release behavior was not influenced by the pH of dissolution medium, dissolution method and paddle stirring rate. The results indicated that the drug release profiles of the optimal formulation had zero-order release character in vitro from 0 to 12 hours.While preparing AH MPOP, AH elementary osmotic pump （AH EOP） was presented. The osmogents, coating level and PEG-400 amount were selected as the causal factors, and the optimum formulation was screened. The drug release profile of AH EOP conformed to the model of zero order in 16h and the linear correlation coefficient was 0．9962．No significant effect was observed on the drug release by the size of orifice.Compared with AH EOP, AH MPOP showed a lag time in release profile, which was resolved through improving the coating formulation. The release performance of AH EOP was stable and controlled release time was prolonged to 24 hours.The stability test results showed that AH EOP was unstable under high humidity conditions, and was stable when exposed to strong light, high temperature. The accelerating experiment indicated that the drug release character, appearance and content of the packaged preparation do not change.With the commercial prolonged release tablet as the reference ,the pharmacokinetic study of self-prepared AH EOP was performed in six dogs. The AUC of AH MPOP and reference tablets were 1436．27±427．96 ng·h/ml and 1415．44±402．23 ng·h/ml respectively. The C_max and T_max of AH MPOP were 105．79±22．20 ng/ml and 7．0±1．1h. The C_max and T_max of reference tablet were 165．05±34．78ng/ml and 5．5±1．5h. The relative bioavailability was 105．1%. The two formulations were bioequivalent according to the results of analysis of variance. The correlation-ship of drug release behavior was studied according to W-N equation. The results indicated that the correlation-ship between vitro and vivo was good （r=0．9362） .