Kakono Chiedza, Witika Bwalya A, Makoni Pedzisai A, Walker Roderick B
Division of Pharmaceutics, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa.
Department of Pharmaceutical Sciences, School of Pharmacy, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
Pharm Dev Technol. 2025 Jun;30(5):646-665. doi: 10.1080/10837450.2025.2516237. Epub 2025 Jun 16.
Levodopa (L-dopa) an effective treatment for Parkinson's disease, but it exhibits low oral bioavailability. Intranasal L-dopa nanosuspensions were manufactured to improve bioavailability using the olfactory and trigeminal delivery routes for direct brain delivery. The development of L-dopa nanocrystals and characterization was undertaken. Nanosuspensions were optimized using Design of Experiments. The L-dopa nanosuspension was produced at 50 °C using sonoprecipitation and mechanical stirring. Water and ethanol were solvent and antisolvent, and Tween 80 and cetyltrimethylammonium bromide, stabilizing agents. The critical quality attributes (CQA) monitored were droplet size (PS), polydispersity index (PDI), Zeta potential (ZP), and percent yield (%), pH and osmolarity of the optimized formulation were monitored. SEM, pXRD, DSC, FTIR, and release were used for further characterization. Short-term stability testing at 4 °C and 22 °C was evaluated for 28 days. The mean PS, PDI, ZP, and % yield of the optimized nanosuspension were 161.4 ± 20.152 nm, 0.383 ± 0.090, +15.45 ± 1.664 mV, and 72.106 ± 0.023%, respectively. In vitro test results for the optimized formulation show the target CQA, had been met. The system may enhance the bioavailability of L-dopa when administered intranasally. studies are required to confirm nose-to-brain transport.
左旋多巴(L-多巴)是治疗帕金森病的一种有效药物,但口服生物利用度较低。为提高生物利用度,利用嗅觉和三叉神经递送途径直接向脑内递送,制备了鼻内给药的左旋多巴纳米混悬液。开展了左旋多巴纳米晶体的研制及表征工作。采用实验设计对纳米混悬液进行优化。通过声沉淀法和机械搅拌,在50℃制备了左旋多巴纳米混悬液。水和乙醇分别作为溶剂和反溶剂,吐温80和十六烷基三甲基溴化铵作为稳定剂。监测的关键质量属性(CQA)包括液滴尺寸(PS)、多分散指数(PDI)、zeta电位(ZP)、产率(%),并监测优化制剂的pH值和渗透压。利用扫描电子显微镜(SEM)、粉末X射线衍射(pXRD)、差示扫描量热法(DSC)、傅里叶变换红外光谱(FTIR)和释放度进行进一步表征。评估了在4℃和22℃下28天的短期稳定性测试。优化后的纳米混悬液的平均PS、PDI、ZP和产率分别为161.4±20.152nm、0.383±0.090、+15.45±1.664mV和72.106±0.023%。优化制剂的体外测试结果表明达到了目标CQA。该系统鼻内给药时可能会提高左旋多巴 的生物利用度。需要进一步研究以确认鼻脑转运。