Sajatovic Martha, Patel Amita, Hebert Mello, Mar Alexander, Moore Richard, Bristow Ali, Farahmand Khody, Siegert Scott
Case Western Reserve University School of Medicine, Cleveland, Ohio; Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
Institute for Psychiatric Education, Dayton, Ohio.
Clin Ther. 2023 Dec;45(12):1222-1227. doi: 10.1016/j.clinthera.2023.09.024. Epub 2023 Nov 10.
One-capsule, once-daily valbenazine is approved for tardive dyskinesia and under evaluation for chorea associated with Huntington's disease, conditions in which patients often experience dysphagia. In vitro studies were conducted to assess the suitability of crushing the contents of valbenazine capsules (40 and 80 mg) for mixing with soft foods or liquids or administration via a gastrostomy tube (G-tube).
In study 1, the dissolution of whole valbenazine capsules and crushed capsule contents were measured serially for 1 hour. In study 2, valbenazine recovery was evaluated after crushed contents were mixed with soft foods, buffer solutions (pH range, 1.2-6.8), and fed-state simulated gastric fluid. In study 3, valbenazine recovery was evaluated after crushed contents were dispersed in water and delivered via a G-tube. In studies 2 and 3, acceptable valbenazine recovery was 90% to 110%.
Study 1 indicated rapid and complete drug release for whole valbenazine capsules and crushed capsule contents, with similar release at 10 minutes (whole, 94%-99%; crushed, 98%-100%) and 60 minutes (whole, 101%-103%; crushed, 101%-102%). Study 2 found acceptable valbenazine recovery within 2 hours of adding crushed capsule contents to tested foods, buffers, or fed-state simulated gastric fluid (recovery, 92%-102%). Study 3 found acceptable valbenazine recovery when crushed contents were added to cold or hot water and delivered via G-tube, with a water cup rinse to capture residual contents (recovery, 91%-97%).
These studies indicate the potential viability of valbenazine formulation(s) that can be added to soft foods or liquids or delivered via G-tube. Such formulations will be important for individuals who require treatment with a vesicular monoamine transporter 2 inhibitor but cannot swallow whole pills.
每日一次服用一粒的缬苯那嗪已被批准用于治疗迟发性运动障碍，目前正在评估其对亨廷顿舞蹈症相关舞蹈症的疗效，这些病症的患者常伴有吞咽困难。进行体外研究以评估碾碎缬苯那嗪胶囊（40毫克和80毫克）内容物与软食或液体混合或通过胃造瘘管（G管）给药的适用性。
在研究1中，连续1小时测量完整缬苯那嗪胶囊和碾碎胶囊内容物的溶出度。在研究2中，将碾碎的内容物与软食、缓冲溶液（pH范围为1.2 - 6.8）和进食状态模拟胃液混合后，评估缬苯那嗪的回收率。在研究3中，将碾碎的内容物分散在水中并通过G管给药后，评估缬苯那嗪的回收率。在研究2和3中，缬苯那嗪的可接受回收率为90%至110%。
研究1表明，完整缬苯那嗪胶囊和碾碎的胶囊内容物药物释放迅速且完全，在10分钟时释放相似（完整胶囊，94% - 99%；碾碎，98% - 100%），在60分钟时也相似（完整胶囊，101% - 103%；碾碎，101% - 102%）。研究2发现，将碾碎的胶囊内容物添加到受试食物、缓冲液或进食状态模拟胃液中2小时内，缬苯那嗪回收率可接受（回收率，92% - 102%）。研究3发现，将碾碎的内容物添加到冷水或热水中并通过G管给药，用水杯冲洗以收集残留内容物时，缬苯那嗪回收率可接受（回收率，91% - 97%）。
这些研究表明了缬苯那嗪制剂添加到软食或液体中或通过G管给药的潜在可行性。这种制剂对于需要用囊泡单胺转运体2抑制剂治疗但无法吞咽整片药物的个体很重要。
