Stability Study of Isoniazid and Rifampicin Oral Solutions Using Hydroxypropyl-Β-Cyclodextrin to Treat Tuberculosis in Paediatrics

Abstract

(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.

Design of functionalized luminescent MOF sensor for the precise monitoring of tuberculosis drug and neonicotinoid pesticide from human body-fluids and food samples to protect health and environment

“…Farina et al discovered that adding ascorbic acid to a rifampicin solution could boost its stability for up to 3 days in ambient conditions. 31 As a result, we prepared a mixture of ascorbic acid and rifampicin in human blood serum and urine separately. Rifampicin was quantified in both the mixtures using the PL titration technique.…”

Quantification of rifampicin loaded into inhaled polymeric nanoparticles by reversed phase high-performance liquid chromatography in pulmonary nonphagocytic cellular uptake

“…Concerning the concentration of ASC used, the lowest concentration (50 μg mL −1 ) was selected because at the highest ASC concentration tested (500 μg mL −1 ) the pH of the RIF solution decreased to a value between 3 and 3.5, at which RIF is unstable. 11 The optimum ratio of MeOH and phosphate buffer for the composition of the mobile phase was 60 : 40 (MeOH: buffer pH 7.0), at a flow rate of 0.8 mL min −1 , at which the running pressure was lower than 25 MPa.…”

The Structural Basis of Mycobacterium tuberculosis RpoB Drug-Resistant Clinical Mutations on Rifampicin Drug Binding

“…MD simulations have been applied in various studies to exhaustively highlight structural mechanisms for differences in ligand bindings between the native protein and mutated targets [ 19 , 26 , 27 , 28 , 30 , 31 ]. Despite experimental evidence showing that RIF effectively binds to the WT rpoB protein at a pH of 7.4 based on physiological conditions [ 41 , 42 ], it remains unclear what the binding state of the drug and its associated conditions are there with the RIF-resistant mutants. Mutations are known to stimulate resistance by associating with the drugs at distinct pH levels [ 43 , 44 , 45 , 46 ].…”