Shah Kiramat Ali, Gao Binbin, Kamal Robia, Razzaq Anam, Qi Sun, Zhu Qiu-Ning, Lina Song, Huang Linyu, Cremin Grainne, Iqbal Haroon, Menaa Farid, Cui Jing-Hao
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), D02YN77 Dublin, Ireland.
Materials (Basel). 2022 May 18;15(10):3591. doi: 10.3390/ma15103591.
Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box-Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF's was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0-t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.
偏头痛是一种神经系统疾病，其特征为严重头痛、视觉厌恶、听觉和嗅觉障碍，并伴有恶心和呕吐。佐米曲普坦（ZMT）是一种强效的5HT1B/1D血清素受体激动剂，常用于治疗偏头痛。它从胃肠道（GIT）的吸收不稳定，但由于肝脏代谢，其口服生物利用度较低（40-45%）。这使其成为口服速溶制剂的理想候选药物。因此，本研究旨在设计和开发含ZMT的口服速溶膜（OFDFs）用于偏头痛治疗。OFDFs采用溶剂浇铸法（SCM）制备，使用普鲁兰多糖（PU）和麦芽糊精（MDX）作为成膜剂，丙二醇（PG）作为增塑剂。该策略采用Box-Behnken实验设计，将PU:MDX的比例和PG的百分比作为自变量。OFDFs的有效性基于以下响应进行测量：5分钟时的药物释放、崩解时间（D-time）和拉伸强度（TS）。还研究了配方因素对ZMT-OFDFs的影响，包括伸长率（%E）、厚度、含水量、吸湿率和耐折性。结果表明成功制备了稳定的ZMT-OFDFs，制备的薄膜中ZMT具有表面均匀性和无定形形状。优化后的配方显示出显著的快速溶解，在前5分钟内超过90%，快速崩解时间为18秒，以及优异的机械性能。与用ZMT胃内（i-g）混悬液治疗的动物（大鼠）相比，用ZMT-OFDFs治疗的动物还观察到最大血浆浓度（C max）和曲线下面积（AUC 0-t）有所改善。含ZMT的共聚物OFDFs是治疗偏头痛的一个令人兴奋的方案，具有很大的潜力。本研究为使用SCM开发ZMT-OFDFs提供了一个有前景的策略。ZMT-OFDFs显示出显著的快速溶解和快速崩解时间，这可能使ZMT-OFDFs成为一种改善患者依从性并缩短偏头痛治疗中ZMT起效时间的吉祥替代方法。
