Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
Drug Dev Ind Pharm. 2010 Nov;36(11):1259-70. doi: 10.3109/03639041003718030.
Ocular bioadhesive minitablets containing gentamicin and vancomycin were developed using different powder mixtures of pregelatinized starch and Carbopol (physical or cospray-dried mixtures).
Drug content, antimicrobial activity, and radical formation of the powders used for tablet preparation were evaluated immediately and 30 days after gamma sterilization. Tablet properties and in vitro drug release from the sterilized minitablets were determined. Storage stability of vancomycin and gentamicin in sterilized bioadhesive mixtures was examined by LC-UV/MS and a microbiological assay, respectively. A bioadhesive powder mixture containing only vancomycin was irradiated by X electron-magnetic radiation to evaluate vancomycin stability following sterilization through irradiation.
The antimicrobial activity of gentamicin against Staphylococcus epidermidis was not altered in comparison to nonsterilized formulations. Only after an overkill dose of 50 kGy, the concentration of vancomycin decreases to an extent that was pharmaceutically significant. No significant difference in radiation stability between drug substance and product (i.e., powder mixture) was observed. A shift in stability profile was not observed at 6 weeks after irradiation. All other degradation products were present only in small quantities not exceeding 1.0%. The in vitro drug release from the minitablets prepared with physical powder mixtures of pregelatinized starch and Carbopol® 974P NF (96 : 4) was faster compared to the cospray-dried mixtures of starch with Carbopol® 974P NF (ratio: 95:5 and 85:15). The electron paramagnetic resonance signals of the radicals formed during sterilization were still visible after storage for 30 days. The slug mucosal irritation test indicated mild irritation properties of the bioadhesive powder mixtures although no tissue damage was observed.
采用不同预胶化淀粉和卡波姆（物理或共喷雾干燥混合物）的粉末混合物，开发含有庆大霉素和万古霉素的眼部生物黏附迷你片剂。
立即和伽马射线灭菌后 30 天评估用于片剂制备的粉末的药物含量、抗菌活性和自由基形成。测定经灭菌的迷你片剂的片剂性质和体外药物释放。分别通过 LC-UV/MS 和微生物测定法研究了灭菌生物黏附混合物中万古霉素和庆大霉素的储存稳定性。用 X 电子-磁辐射照射仅含有万古霉素的生物黏附粉末混合物，以评估通过辐照灭菌后万古霉素的稳定性。
与非灭菌制剂相比，庆大霉素对表皮葡萄球菌的抗菌活性没有改变。仅在超过 50 kGy 的致死剂量下，万古霉素的浓度才会降低到具有药学意义的程度。药物物质和产品（即粉末混合物）之间没有观察到辐射稳定性的显著差异。辐照后 6 周未观察到稳定性曲线的偏移。所有其他降解产物仅以小量存在，不超过 1.0%。用预胶化淀粉和 Carbopol®974P NF（96:4）的物理粉末混合物制备的迷你片剂的体外药物释放速度比淀粉与 Carbopol®974P NF（比例：95:5 和 85:15）的共喷雾干燥混合物更快。灭菌过程中形成的自由基的电子顺磁共振信号在储存 30 天后仍然可见。贴剂黏膜刺激试验表明生物黏附性粉末混合物具有轻度刺激性质，尽管没有观察到组织损伤。
