PREPARATION AND CHARACTERIZATIONS OF AMBROXOL SR TABLET

• Main Authors: Hsu Tien-Tzu, 許天賜
• Other Authors: Sheu Ming-Thau
• Format: Others
• Language: en_US
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/06714429726771998349

碩士 === 臺北醫學大學 === 藥學系 === 91 === The purpose of this study was to develop a sustained release tablet of ambroxol that to be taken once daily. The optimized ambroxol sustained release tablet, Amsolvon SR tablet as trade name, was prepared via a melt-coating granulation technique and its functionality was characterized based on the following tests: weight variation, content uniformity, hardness, friability and dissolution tests. In vitro dissolution studies show that the drug release rate and amount are not affected by particle size of ambroxol-Compritol 888 melted granules and tabletting speeds. But the hardness of ambroxol SR tablets is influenced by particle sizes and tabletting speeds. Low tabletting speed and large particle size may produce more compact tablets; this can be attributed to the plastic deformation characteristic of the tablet excipients. Finally the particle size of <420 mm of ambroxol-Compritol 888 melted particles were selected in terms of higher production yield. The selected melted particles were mixed thoroughly and tabletted at 20 rpm to obtain Amsolvon SR tablets. The dissolution profile of Amsolvon SR tablets was more similar with PR-ABX capsules than Mucosolvan capsules in all three dissolution media. The drug release mechanism of ambroxol from Amsolvon SR tablets can be described by Higuchi diffusion model. The long-term and accelerated stability tests both showed that Amsolvon SR tablet was stable and its tentative shelf life was 4 years at least. Pharmacokinetic pilot study in four healthy male human subject after oral administration with multiple doses of Amsolvon SR tablets show that the formulation was successful in providing slow release of ambroxol and has mean±SD AUC0-24 of 1559.6±149.4 ng/mL·hr, Cmax of 104.63±6.34 ng/mL, Cmin of 38.83±13.86 ng/mL, Cav of 64.98±6.22 ng/mL, fluctuation of 1.03±0.30, AUMC0-24 of 16246±1784 ng/mL·hr2, MRT0-24 of 10.41±0.46 hr, Tmax of 7.50±1.29 hr, Kel of 0.0673±0.0091 hr-1, T1/2 of 10.46±1.53 hr, CL/F of 48.40±4.33 L/hr, and Vd/F of 735.45±162.44 L. The efficacy and safety of this ambroxol SR tablet (Amsolvon SR tablet) dosage form are currently being evaluated in clinical trials; it may be expected to provide optimum therapeutic efficacy and improve patient’s compliance in the future.