چکیده (انگلیسی):

The aim of the present investigation was to develop a novel
dosage form of rifampicin and isoniazid to minimize degradation
of rifampicin in acidic medium and to modulate
the release of rifampicin in the stomach and isoniazid in the
intestine. Gastroretentive tablets of rifampicin (150 mg) were
prepared by the wet granulation method using hydroxypropyl
methylcellulose, calcium carbonate, and polyethylene glycol
4000. The granules and tablets of rifampicin were characterized.
Hard gelatin capsules (size 4) containing a compacted
mass of isoniazid (150 mg) and dicalcium phosphate (75 mg)
were enteric coated. Two tablets of rifampicin and 1 capsule
(size 4) of isoniazid were put into a hard gelatin capsule
(size 00). The in vitro drug release and in vitro drug degradation
studies were performed. Rifampicin was released over
4 hours by zero-order kinetics from the novel dosage form.
More than 90% of isoniazid was released in alkaline medium
in 30 minutes. The results of dissolution studies with
the US Pharmacopeia XXIII method revealed that a substantial
amount of rifampicin was degraded from the immediate
release capsule containing rifampicin and isoniazid
powder owing to drug accumulation in the dissolution vessel
and also to the presence of isoniazid. The degradation
of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested
(3.6%-4.8% degradation of rifampicin at 4 hours)
because of the minimization of physical contact between
the 2 drugs and controlled release of rifampicin in acidic
medium in the modified Rossett-Rice apparatus. This study
concludes that the problem of rifampicin degradation can be
alleviated to a certain extent by this novel dosage form.