Khizer Zara, Akram Muhammad R, Tahir Muhammad Azam, Liu Weidong, Lou Shan, Conway Barbara R, Ghori Muhammad Usman
Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.
College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
Pharmaceuticals (Basel). 2023 Feb 28;16(3):372. doi: 10.3390/ph16030372.
Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the upper small intestine, resulting in poor bioavailability. We aimed to develop an extended release, intragastric floating system to overcome this drawback. For this purpose, plasticiser-free filaments of PEO (polyethylene oxide) and the drug (gabapentin) were developed using hot melt extrusion. The filaments were extruded successfully with 98% drug loading, possessed good mechanical properties, and successfully produced printed tablets using fused deposition modelling (FDM). Tablets were printed with varying shell numbers and infill density to investigate their floating capacity. Among the seven matrix tablet formulations, F2 (2 shells, 0% infill) showed the highest floating time, i.e., more than 10 h. The drug release rates fell as the infill density and shell number increased. However, F2 was the best performing formulation in terms of floating and release and was chosen for in vivo (pharmacokinetic) studies. The pharmacokinetic findings exhibit improved gabapentin absorption compared to the control (oral solution). Overall, it can be concluded that 3D printing technology is an easy-to-use approach which demonstrated its benefits in developing medicines based on a mucoadhesive gastroretentive strategy, improving the absorption of gabapentin with potential for the improved management of OAB.
膀胱过度活动症（OAB）是一种有症状的复杂病症，其特征为尿频、夜尿，以及伴有或不伴有尿急的尿失禁。加巴喷丁是治疗OAB的有效药物，但其吸收窗口狭窄令人担忧，因为它优先从小肠上段吸收，导致生物利用度较差。我们旨在开发一种缓释胃内漂浮系统来克服这一缺点。为此，采用热熔挤出法制备了不含增塑剂的聚环氧乙烷（PEO）长丝和药物（加巴喷丁）。成功挤出了载药量为98%的长丝，其具有良好的机械性能，并使用熔融沉积建模（FDM）成功制备了打印片剂。通过打印不同壳层数和填充密度的片剂来研究其漂浮能力。在七种基质片剂配方中，F2（2层壳，0%填充）显示出最长的漂浮时间，即超过10小时。药物释放速率随着填充密度和壳层数的增加而降低。然而，就漂浮和释放而言，F2是性能最佳的配方，并被选用于体内（药代动力学）研究。药代动力学研究结果显示，与对照组（口服溶液）相比，加巴喷丁的吸收有所改善。总体而言，可以得出结论，3D打印技术是一种易于使用的方法，在基于粘膜粘附性胃滞留策略开发药物方面显示出其优势，可改善加巴喷丁的吸收，有望改善OAB的治疗效果。
