摘要
目的:制备复方倍他米松混悬注射液,确定其处方工艺。方法:将微晶化法制得的二丙酸倍他米松微粒加于灭菌基质液中均质混悬,然后加入过0.2μm滤膜的倍他米松磷酸钠盐溶液搅拌混匀,制得复方倍他米松混悬注射液;以渗透压、沉降体积比、重分散次数、含量及有关物质为考察指标,采用单因素试验筛选微晶化工艺中溶剂无水乙醇与反溶剂注射用水的比例,用正交设计筛选优化样品处方中羟苯甲酯、聚山梨酯80、氯化钠及羧甲基纤维素钠的用量;并对样品进行稳定性研究。结果:无水乙醇-注射用水比例为1∶10,以0.1%羟苯甲酯为絮凝剂,0.05%聚山梨酯80为润湿剂,0.15%氯化钠为渗透压调节剂,1.0%羧甲基纤维素钠为助悬剂,采用无菌生产工艺制得样品;其渗透压为297 mOsm/kg,沉降体积比为0.13,重分散次数为15次,二丙酸倍他米松含量为99.3%,倍他米松磷酸钠含量为100.0%,有关物质为0.38%;样品为絮状振摇易分散的混悬型无菌注射剂,加速6个月和长期24个月试验的各指标与0 d时比较均未见明显变化。结论:该制剂制备处方合理、方法可行、稳定性良好,避免了终端高温灭菌可能造成的主药降解、微晶聚结成块。
OBJECTIVE： To prepare Compound betamethasone suspension injection, and to determine its formulation and technology. METHODS： The betamethasone dipropionate particles prepared by crystallization method was added into a homogeneous suspension, and mixed with betamethasone sodium phosphate solution filtered by 0.2 μm membrane. Compound betamethasone suspension injection was prepared. Using osmotic pressure, sedimentation volume ratio, the times of redispersion, the drug content and the related substances as index, the amount of absolute ethyl alcohol and antisolvent water for injectione in crystallization technology were screened by single factor test. The amounts of methylparaben, polysorbate 80, sodium chloride and carboxymethyl cellulose in formulation were screened by orthogonal test, and the stability of samples was studied. RESULTS： The ratio of absolute ethyl alcohol and water for injectione was 1 ： 10; the samples were prepared by aseptic production process, using 0.1% methylparaben as flocculant, 0.05% polysorbate 80 as wetting agent, 0.15% sodium chloride as osmotic pressure regulator and 1.0% carboxymethylcellulose sodium as suspending agent; osmotic pressure was 297 mOsm/kg, sedimentation volume ratio was 0.13, the times of redispersion was 15 times, the content of betamethasone dipropionate was 99.3%, that of betamethasone sodium phosphate was 100.0% and that of related substances was 0.38%. The sample was floceulent sterile injection which can be dispersed easily by shaking. The sample was stable in 6 month acceleration test and 24 month long-term test, compared with 0 d tests. CONCLUSIONS： The preparation is reasonable in formulation, feasible in preparation technology and stable so as to avoid main component degradation and microcrystal coalescence due to terminal heat sterilization.
出处
《中国药房》
CAS
CSCD
2014年第25期2346-2348,共3页
China Pharmacy
关键词
复方倍他米松混悬注射液
处方
无菌工艺
制备
Compound betamethasone suspension injection
Formulation
Aseptic technology
Preparation
