Stability Study of Isoniazid and Rifampicin Oral Solutions Using Hydroxypropyl-Β-Cyclodextrin to Treat Tuberculosis in Paediatrics
Santoveña-Estévez A, Suárez-González J, Cáceres-Pérez AR, Ruiz-Noda Z, Machado-Rodríguez S, Echezarreta M, Soriano M, Fariña JB.
Pharmaceutics. 2020 Feb;12(2):195.
Publisher: MDPI AG© 2020 by the authors
(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% w/v 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.
Solubility studies of rifampicin and hydroxypropyl-β-cyclodextrin for pediatric formulations
Echezarreta M, Ruiz-Noda Z, Suárez-González J, Soriano M, Santoveña-Estévez A, Fariña JB.
6th European Conference on Cyclodextrins, October 2-4, 2019
Publisher: Reproduced with permission.
© Universidad de La Laguna
In this work the complexation properties of a hydroxypropyl-β-cyclodextrin (HPBCD) with an antituberculous drug of low solubility and low intestinal permeability classified as BCD Class IV, like as is Rifampicin (R), are studied. Changes of the bioavailability of R in at fixed dose combination (FDC) has been widely recognized in numerous scientific publications. Pediatric formulations have big limitations and are being of special interest those liquid oral pharmaceutical preparations of a single dose. Our aim is to analyze the ability of this cyclodextrin derivative to solubilize oral pediatric doses of Rifampicin.
R form inclusion complexes with HPBCD of different solubilities in phosphate buffer solutions at different pHs. By complexation process, the solubility of R increase between two to seven times. The ionization of this drug defines the interaction with this cyclodextrin derivative and also the final solubility of the drug due to self-association effects drug-drug and cyclodextrin.