Santoveña-Estévez Ana, Suárez-González Javier, Cáceres-Pérez Amor R, Ruiz-Noda Zuleima, Machado-Rodríguez Sara, Echezarreta Magdalena, Soriano Mabel, Fariña José B
Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna (Tenerife), Spain.
Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna, 38200 La Laguna (Tenerife), Spain.
Pharmaceutics. 2020 Feb 24;12(2):195. doi: 10.3390/pharmaceutics12020195.
(1) Background: First-line antituberculosis treatment in paediatrics entails the administration of Isoniazid, Pyrazinamide, and Rifampicin. This study examines the possibility of developing a combined dose liquid formulation for oral use that would facilitate dose adjustment and adherence to treatment for younger children. (2) Methods: The active pharmaceutical ingredients stability under in vitro paediatric digestive pH conditions have been checked. The samples were studied as individual or fixed combined paediatric dosages to determine the pH of maximum stability. The use of hydroxypropyl-β-cyclodextrin to improve Rifampicin solubility and the use of ascorbic acid to increase the stability of the formulation have been studied. (3) Results: Maximum stability of combined doses was determined at pH 7.4, and maximum complexation at pH 8.0. Taking this into account, formulations presented the minimum dose of two active pharmaceutical ingredients dissolved. The addition of ascorbic acid at 0.1% / enables the detection of a higher remaining quantity of both drugs after three days of storage at 5 °C. (4) Conclusions: a formulation which combines the minimum paediatric dosages dissolved recommended by WHO for Isoniazid and Rifampicin has been developed. Future assays are needed to prolong the stability of the formulation with the aim of incorporating Pyrazinamide to the solution.
(1) 背景：儿科一线抗结核治疗需要使用异烟肼、吡嗪酰胺和利福平。本研究探讨开发一种口服联合剂量液体制剂的可能性，该制剂将有助于年幼儿童调整剂量并坚持治疗。(2) 方法：已检查活性药物成分在体外儿科消化pH条件下的稳定性。将样品作为单独或固定的儿科联合剂量进行研究，以确定最大稳定性的pH值。研究了使用羟丙基-β-环糊精提高利福平溶解度以及使用抗坏血酸提高制剂稳定性的情况。(3) 结果：联合剂量在pH 7.4时具有最大稳定性，在pH 8.0时具有最大络合度。考虑到这一点，制剂呈现出两种活性药物成分溶解的最小剂量。添加0.1%的抗坏血酸可使两种药物在5℃储存三天后检测到更高的剩余量。(4) 结论：已开发出一种将世界卫生组织推荐的异烟肼和利福平溶解的最小儿科剂量联合起来的制剂。需要进行进一步的试验以延长制剂的稳定性，目的是将吡嗪酰胺加入溶液中。
