Chiclana-Rodríguez Blanca, Garcia-Montoya Encarnacion, Romero-Obon Miquel, Rouaz-El-Hajoui Khadija, Nardi-Ricart Anna, Suñé-Pou Marc, Suñé-Negre Josep M, Pérez-Lozano Pilar
Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain.
Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology Research Group, Bellvitge Biomedical Research Institute (IDIBELL), Av. Gran Via de l'Hospitalet, 199-203, 08090 Barcelona, Spain.
Pharmaceutics. 2023 Dec 25;16(1):30. doi: 10.3390/pharmaceutics16010030.
Carvedilol (CARV) is a blocker of α- and β- adrenergic receptors, used as an "off-label" treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.
卡维地洛（CARV）是一种α和β肾上腺素能受体阻滞剂，在儿科用作心血管疾病的“非标签”治疗药物。目前，尚无市售的适合儿科使用的卡维地洛液体制剂，因此有必要进行开发。适口性（对气味、味道和余味的感受）是儿科制剂开发过程中需要考虑的一个关键方面，因为只有适口性好的制剂在该人群中才具有足够的可接受性。因此，本研究的目的是通过体内味觉评估（ID编号PR103/22）来评估不同卡维地洛制剂的适口性和可接受性，以便选择适口性评分最高的卡维地洛制剂。卡维地洛制剂的制备基于参考的1mg/mL卡维地洛溶液，该溶液含有苹果酸作为增溶剂。随后，加入三氯蔗糖和调味剂并混合，直至完全溶解到相应制剂中。成年志愿者参与了本研究，并通过问卷和感官测试评估了各种卡维地洛制剂的味道和气味。以10分制衡量的平均适口性评分从未调味对照的1.60分提高到评分最高的调味制剂的7.65分。此外，优化后的卡维地洛制剂的苦味从66.67%降至17.86%，味道愉悦度从25/100提高到73/100。这种优化后的卡维地洛制剂除了含有两种适合儿科的适当浓度的调味剂外，还含有甜味剂三氯蔗糖。此外，对优化后的卡维地洛制剂在25、30和40°C下进行了6个月的物理化学和微生物稳定性评估，以及在25°C下15天的使用稳定性评估，其结果得到了证实。因此，我们成功开发了一种适口的卡维地洛液体溶液，该溶液含有适合儿科的辅料，并且在所研究的条件下是稳定的。
