Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

摘要：个性化医疗在药物治疗领域的重要性日益凸显，因其可实现药物治疗的个体化定制，以获得最佳的患者应答效果。口腔速溶膜（Orodispersible Film，ODF）便于在医院内制备，可灵活调整剂量以适配个体需求，尤其适用于存在吞咽障碍或无法摄入液体的患者。本研究将盐酸舍曲林（Sertraline Hydrochloride，SRT）溶解于多种助溶剂中，随后以五种亲水聚合物——聚乙烯醇（Polyvinyl Alcohol，PVA）、羟乙基纤维素（Hydroxyethyl Cellulose，HEC）、羟丙基甲基纤维素E5 LV（Hydroxypropyl Methylcellulose E5 LV，HPMC E5 LV）、海藻酸钠（Sodium Alginate，NaAlg）以及明胶——为基质，分别以2%和4%的浓度制备了不同的盐酸舍曲林口腔速溶膜，并对其进行了表征。对制备所得的各项结果进行响应面分析，以获取合意性评价结果，从而得到优化后的处方。本研究以4% PVA与2% HEC按不同比例复配制备了复合口腔速溶膜，并向最优处方中加入作为成孔剂的氯化钾（Potassium Chloride，KCl），以探究其对药物溶出的促进作用。编号为F14的处方（含4% PVA与2% HEC以2:1比例复配，且添加5% KCl）展现出最优的理化性质：pH值适宜（5.6）、崩解时限为6秒、耐折性良好，且在15分钟内可释放91%的SRT。盐酸舍曲林口腔速溶膜是一种极具应用前景的给药系统，可应用于个性化医疗框架下的抑郁症治疗。