Hollenbeck R Gary, Fahmy Raafat, Martinez Marilyn N, Ibrahim Ahmed, Hoag Stephen W
University of Maryland, School of Pharmacy, Department of Pharmaceutical Sciences, 20 N Pine Street, Baltimore, Maryland, 21201, USA.
Office of Generic Animal Drugs, Center for Veterinary Medicine, US Food and Drug Administration, Rockville, Maryland, 20855, USA.
AAPS PharmSciTech. 2025 Jan 22;26(1):43. doi: 10.1208/s12249-024-03030-2.
Dosage forms containing Ivermectin (IVER) and Praziquantel (PRAZ) are important combination drug products in animal health. Understanding the relationship between products with differing in vitro release characteristics and bioequivalence could facilitate generics. The goal of this study was to create granulations for each active ingredient, with similar release mechanisms, but substantially different in vitro release rates, and then compressing these granulations into tablets with differing release rates. Four granulation formulations were created: fast and modified release for PRAZ and IVER, respectively. The manufacturing process used high shear wet granulation and fluid bed drying, milling and sieving. Solid components, including the granulating agent, were blended in a high shear granulator and then water or a hydroalcoholic solution was added to activate the binder and initiate granule formation. Drying in a fluid bed with inlet air temperature set for 70°C and inlet air volume adjusted as required to maintain fluidization. Milling was performed in a cone mill and classification of final product was done using a vibratory sieve shaker with 18, 20, 40, and 60 mesh sieves. Formulations and processing approaches were successfully developed to produce a collection of PRAZ and IVER granules with differing particle size distributions and in vitro release characteristics. Differences in drug content in the classified granulations were observed and attributed to the low surface energy of PRAZ and the different approaches used to incorporate the active ingredients. The granulations were compressed via compaction simulator and the results show the monolithic tablets had four different release profiles.
含有伊维菌素（IVER）和吡喹酮（PRAZ）的剂型是动物健康领域重要的复方药物产品。了解具有不同体外释放特性的产品之间的关系以及生物等效性有助于仿制药的研发。本研究的目的是为每种活性成分制备具有相似释放机制但体外释放速率有显著差异的颗粒，然后将这些颗粒压制成具有不同释放速率的片剂。制备了四种颗粒制剂：分别为PRAZ和IVER的速释和缓释制剂。制造过程采用高剪切湿法制粒、流化床干燥、研磨和筛分。将包括制粒剂在内的固体成分在高剪切制粒机中混合，然后加入水或水醇溶液以活化粘合剂并引发颗粒形成。在流化床中干燥，设定进风温度为70°C，并根据需要调节进风量以保持流化状态。在锥形磨中进行研磨，使用18目、20目、40目和60目筛网的振动筛对最终产品进行分级。成功开发了制剂和加工方法，以制备一系列具有不同粒度分布和体外释放特性的PRAZ和IVER颗粒。观察到分级颗粒中药物含量的差异，并归因于PRAZ的低表面能以及用于加入活性成分的不同方法。通过压片模拟器对颗粒进行压制，结果表明整体片剂具有四种不同的释放曲线。
