Preparation And Quality Study Of Ambroxol Hydrochloride Sustained-release Tablets

Ambroxol Hydrochloride is a new generation of antitussive and expectorant medicine. The drug has quite valid curative effect and seldom poisonous effect. In domestic expectorant medicine market, it now possesses the largest share, which will become larger in the future. With so brilliant market prospects, the development of new forms of dosage has significant social and economic benefits.The popular dosage forms of ambroxol hydrochloride listed in the domestic market are oarl solutions, tablets, capsules, sustained-release capsules and so on. Till now, no report of sustained-release tablet has been appeared on the market. This paper will make a systematic research on the production process and quality control of prepare ambroxol hydrochloride hydrophilic gel matrix tablets through experiment.In this paper, different excipients such as hydroxypropyl methylcellulose (HPMC), sodium alginate, lactose, microcrystalline cellulose(MCC), pregelatinized starch, PEG6000, talc powder and magnesium stearate were selected to investigate their impact affect on the quality of ambroxol hydrochloride sustained-release tablets.Based on the result of single-factor tests, the formulation of sustained-release tablets was determined by orthogonal experiment which was designed to optimize the formulation of ambroxol hydrochloride sustained-release tablets. At last, HPMC K4M and HPMC K15M was selected as the basic matrix material, lactose was selected as the filling material, PEG6000 was selected as the pore former, magnesium stearate was selected as the lubricant, aerosol was selected as the glidant and 70% alcohol was choosed as the adhesive. Also, the method of wet granulation tableting was selected for the preparation of hydrophilic gel matrix tablets which could maintain releasing in vitro for over 8 hours.Established quality standards for internal control of ambroxol hydrochloride sustained-release tablets and did research on its stability study. The result of the stress test shows that ambroxol hydrochloride sustained-release tablets, which are prepared according to the optimal formulation and technology, are stable under high temperature, high humidity and intensive light. Both the accelerated test and the long-term test show that the quality of the ambroxol hydrochloride sustained-release tablet is stable, and no obvious changes occurred to the indices.In the bioequivalence study, ambroxol hydrochloride sustained-release capsule that pruducted by Pharma Group Beijing Zizhu Pharmaceutical Co., Ltd was used as the reference formulation, and a HPLC method was established for the determination of ambroxol hydrochloride concentrations of plasma. The method of double two-cycle cross-preparation and specific software was adopted to calculate pharmacokinetic parameters and statistical analysis. Test results show that the self-made formulation is bioequivalent with the reference formulation. Self-made ambroxol hydrochloride sustained-release tablet is a good sustained-release dosage form, and it is good in the effect of in vitro-in vivo release.