Agomelatine Transdermal System Product Cycle: Development, Material/Process Screening, Optimization, Characterization, Delivery Mechanics and Irritation study on Rat.

Punitkumar Rathod, Anita Lalwani
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Abstract

Introduction/objective: Agomelatine (AGT) is used for the treatment of major depressive disorder in adults. Agomelatine is highly susceptible to first-pass metabolism, and it has less than 5% oral bioavailability. Therapy for major depressive disorder extends for a long period and every time, additional caregivers are required to remind and manage the timely dosing of oral medicine to patients. In such cases, once a week, administration of agomelatine via transdermal patch dosage form provides major patient benefits and lowers overall therapy costs.

Methods: An agomelatine transdermal patch was prepared using the solvent evaporation method using the LTE-S Werner Mathis AG coater and dryer. A patch was prepared using silicon adhesive after screening different pressure-sensitive adhesives like acrylate, polyisobutylene, and silicon. To make a crystal-free patch, the concentration of povidone k-29/32 was optimized in preliminary trials. To deliver the drug over a 7-day period, propylene glycol monolaurate (PGML) was identified from different penetration enhancers. Three factors optimization was carried out, like the concentration of povidone k-29/32, the concentration of PGML, and the mixing time of the blend using the Box Behnken design. 3D surface response curves and contour plots were derived using Design Expert and Minitab software. From overlay plots, design spaces were identified.

Result: The optimized AGT patch has good adhesion properties along with a desirable flux of 4.63 μg/cm2/h on human cadaver skin along with a lower residual drug. There was no impact of heat flux studies on normal conditions, hence justifying the in-use condition of the patient population during hot showers, baths, and saunas. AGT Patch was also non-irritating in skin irritation studies performed on Wistar albino rats.

Conclusion: It was concluded that agomelatine transdermal patches can be manufactured using silicon adhesive, povidone k-29/32, and propylene glycol monolaurate for the treatment of major depressive disorder and will be the most convenient and cost-effective therapy for the patient.

阿戈美拉汀透皮系统产品周期:开发,材料/工艺筛选,优化,表征,给药机制和大鼠刺激研究。
简介/目的:阿戈美拉汀(AGT)用于治疗成人重度抑郁症。阿戈美拉汀对首过代谢非常敏感,口服生物利用度低于5%。重度抑郁症的治疗需要很长一段时间,每次都需要额外的护理人员提醒和管理及时给患者口服药物的剂量。在这种情况下,每周一次,通过透皮贴剂给药阿戈美拉汀为患者提供了主要的益处,并降低了总体治疗成本。方法:采用溶剂蒸发法制备阿戈美拉汀透皮贴剂,采用LTE-S Werner Mathis AG涂布干燥机。对丙烯酸酯、聚异丁烯、硅等不同的压敏胶进行筛选,制备了硅胶贴片。为了制备无晶贴片,在初步试验中优化了聚维酮k-29/32的浓度。为了在7天的时间内给药,从不同的渗透促进剂中鉴定出了单月桂酸丙二醇(PGML)。采用Box - Behnken设计对聚维酮k-29/32的浓度、PGML的浓度、共混时间3个因素进行优化。利用Design Expert和Minitab软件绘制三维曲面响应曲线和等高线图。从覆盖的地块中,确定了设计空间。结果:优化后的AGT贴片在人体皮肤上具有良好的粘附性能,药量为4.63 μg/cm2/h,残留药物量较小。热通量研究在正常条件下没有影响,因此证明了患者在热淋浴、泡澡和桑拿期间的使用条件。在对Wistar白化大鼠进行的皮肤刺激研究中,AGT贴片也无刺激性。结论:用硅胶、聚维酮k-29/32、单月月酸丙二醇制备阿戈美拉汀透皮贴剂治疗重度抑郁症是最方便、最经济的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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