Study Of Ambroxol Hydrochloride Chewable Tablets

Ambroxol hydrochloride (AbH), the active metabolic product of bromhexine is a commonly used apophlegmatisant with high efficiency and low toxicity. In order to increase patient compliance, its preparation of chewable tablet is investigated in this thesis.In this study, firstly different proportions of EUDRAGIT L100-55 were tested as vehicle to prepare the inclusion complex of AbH by solvent method. And its dispersed state in carrier was also analyzed through differential scanning calorimetry (DSC). As a result, AbH is proved to exist in amorphous form.Secondly, several commonly used disintegrating agents such as L-HPC, CMS-Na, PVPP and CCMC-Na were also screened to attain ideal dissolution. It had been showed that among these selected disintegrating agents, PVPP and CCMC-Na were the better choice than others, whereas PVPP was the best. The optimized formulation was decided through orthogonal experiments in this paper.Thirdly, the quality standards of AbH chewable tablet were formulated in which the examining indexes included property, identification, related substance, content and dissolution. And three batches products of pilot scale were detected according to above-mentioned standards and some positive results available.Then tests of influencing factors, accelerated and long-term stability were also performed to investigate its property, content, related substance and dissolution, etc. No obvious change of these examining indexes was observed in three batches products in marketing package after 6 month accelerated stability test and 24 month long-term stability test. So the period of validity of this product was temporarily determined as 24 month.At last, in a study of dicycle duration, twenty healthy male volunteers were enrolled in a randomized cross-over trial with a single dose of 60mg reference and test preparation. The plasma concentration of ambroxol hydrochloride is detected by HPLC/MS. And relevant pharmacokinetic parameters and bioavailability were assessed using DAS 1.0 software. It has been showed that the Cmax, Tmax, AUC0 and t1/2 of reference and test preparations are 108.81±24 and 117.69±25.27 ng·mL; 1.73±0.50 and 1.58±0.51 h; 849.81±220 and 842.72±164.4040 ng·mL^-1·h; 7.39±0.97 and 7.39±0.97 h respectively.