Pharmaceutical formulation of a fixed-dose anti-tuberculosis combination.

SETTING: Department of Pharmacy and Pharmacology, University of the Witwatersrand. Despite the availability of highly effective treatment regimens for tuberculosis (TB), the cure rate still remains relatively low. This may be attributed to the high incidence of patient non-compliance, which subsequently leads to the emergence of multidrug-resistant TB (MDR-TB). To avoid the problem of further creation and propagation of MDR-TB, it may be proposed that patients should be given fixed-dose combinations of anti-tuberculosis drugs whenever self-administration is permitted. OBJECTIVE: To optimise an anti-tuberculosis extemporaneous powder formulation for suspension in order to develop a fixed combination of rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride as a powder to be reconstituted with water by the patient prior to administration. METHODS: Different suspending agents were evaluated for their influence on powder flow properties, and sediment volume on the powder blends. Sodium starch glycolate was selected as the suspending agent because of its favourable powder flow properties and sediment volume produced. The dissolution characteristics of the extemporaneous powder for suspension were also compared to the dissolution profiles of commercially available anti-tuberculosis tablet dosage forms. RESULTS: The powder for suspension for rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride all compared favourably to the dissolution rate from the commercially available tablet dosage forms.