Ogbonna John Dike N, Cunha Edite, Attama Anthony A, Ofokansi Kenneth C, Ferreira Helena, Pinto Susana, Gomes Joana, Marx Ítala M G, Peres António M, Lobo José Manuel Sousa, Almeida Isabel F
Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, University of Nigeria, Nsukka 410001, Nigeria.
Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
Pharmaceuticals (Basel). 2022 Oct 27;15(11):1331. doi: 10.3390/ph15111331.
Designing oral formulations for children is very challenging, especially considering their peculiarities and preferences. The choice of excipients, dosing volume and palatability are key issues of pediatric oral liquid medicines. The purpose of the present study is to develop an oral pediatric solution of a model bitter drug (ranitidine) following a patient centric design process which includes the definition of a target product profile (TPP). To conclude on the matching of the developed solution to TPP, its chemical and microbiological stability was analyzed over 30 days (stored at 4 °C and room temperature). Simulation of use was accomplished by removing a sample with a syringe every day. Taste masking was assessed by an electronic tongue. The developed formulation relied on a simple taste masking strategy consisting in a mixture of sweeteners (sodium saccharine and aspartame) and 0.1% sodium chloride, which allowed a higher bitterness masking effectiveness in comparison with simple syrup. The ranitidine solution was stable for 30 days stored at 4 °C. However, differences were noted between the stability protocols (unopened recipient and in-use stability) showing the contribution of the simulation of use to the formation of degradation products. Stock solution was subjected to acid and alkali hydrolysis, chemical oxidation, heat degradation and a photo degradation stability assessment. The developed pediatric solution matched the TPP in all dimensions, namely composition suitable for children, preparation and handling adapted to hospital pharmaceutical compounding and adequate stability and quality. According to the results, in-use stability protocols should be preferred in the stability evaluation of pediatric formulations.
设计儿童口服制剂极具挑战性，尤其是考虑到他们的特点和偏好。辅料的选择、给药体积和适口性是儿科口服液体制剂的关键问题。本研究的目的是遵循以患者为中心的设计流程，开发一种模型苦味药物（雷尼替丁）的儿科口服溶液，该流程包括定义目标产品概况（TPP）。为了确定所开发的溶液与TPP的匹配情况，在30天内（储存于4℃和室温）分析了其化学和微生物稳定性。通过每天用注射器取出样品来完成使用模拟。用电子舌评估掩味效果。所开发的制剂依靠一种简单的掩味策略，即甜味剂（糖精钠和阿斯巴甜）与0.1%氯化钠的混合物，与单纯糖浆相比，其掩苦效果更高。雷尼替丁溶液在4℃储存30天稳定。然而，在稳定性方案（未开封容器和使用中的稳定性）之间发现了差异，表明使用模拟对降解产物形成的影响。对储备溶液进行了酸碱水解、化学氧化、热降解和光降解稳定性评估。所开发的儿科溶液在所有方面均符合TPP，即适合儿童的成分、适应医院药物配制的制备和处理以及足够的稳定性和质量。根据结果，在儿科制剂的稳定性评估中应优先采用使用中的稳定性方案。
