Pharmaceutical formulation of a fixed-dose anti-tuberculosis combination.
METHODS
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.
Danckwerts
M P
MP
Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, South Africa. danckwertsmp@therapy.wits.ac.za
Ebrahim
S
S
Pillay
V
V
D000284:Administration, Oral; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004339:Drug Compounding; D004977:Ethambutol / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D005240:Feasibility Studies; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D011718:Pyrazinamide / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D005079:Excipients; D011208:Powders; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin