Ranmal Sejal R, Lavarde Marc, Wallon Elodie, Issa Samar, Taylor Walter R, Nguyen Ngoc Pouplin Julie L A, Tuleu Catherine, Pensé-Lhéritier Anne-Marie
UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Ecole de Biologie Industrielle-EBI, UPR EBInnov®, 49 Avenue des Genottes CS90009, 95895 Cergy, France.
Pharmaceutics. 2023 Jul 4;15(7):1879. doi: 10.3390/pharmaceutics15071879.
Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74-3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.
伯氨喹是一种用于疟疾传播阻断和根治的重要抗疟药物，但目前尚无适合儿童使用的适当剂量剂型。成人剂型的片剂常被碾碎并溶于水中以获取所需剂量，这会暴露药物的苦味。作为开发儿童用伯氨喹（DPP）项目的一部分，本研究采用了一种响应式感官药剂学方法，通过整合实时剂型开发和临床前味觉评估来开发可口的、添加了调味剂的伯氨喹片剂。采用实验设计（DoE）方法，与经过培训的专业感官评估人员一起筛选不同的掩味剂和辅料混合物，以盐酸奎宁作为模型苦味剂。使用15毫克的最高伯氨喹剂量，让未经训练的评估人员对选定的原型制剂混合物的掩味效果进行验证。以离散的11分制衡量，平均苦味强度评分从无味对照品的7.04降至制剂混合物的2.74 - 3.70。三氯蔗糖对苦味抑制和改善适口性的影响最大。已开发出两种不同的调味系统，其在儿科患者中的可接受性将作为即将在非洲进行的验证性现场临床试验的一部分进行评估。
