Background: Rifampicin is known to degrade at the acidic pH of the stomach, especially in
the presence of isoniazid. Although isoniazid also degrades partially, its degradation is reversible.
Objective: Presently, we provide a proof of the fact that the simultaneous oral administration of rifampicin
(RIF), upon incorporation into solid lipid nanoparticles (RIF-SLNs), with isoniazid (INH) overcomes
its INH-induced degradation and improves its oral bioavailability in rats.
Methods: Solid lipid nanoparticles of RIF (RIF-SLNs) were prepared using a novel and patented
method. The effect of INH was investigated on in vivo bioavailability of RIF both in its free and encapsulated
(RIF-SLNs) form, after oral administration to rats.
Results: Cmax and AUC0-∞ of RIF increased 158 % and 125 %, respectively, upon incorporation into
SLNs versus free RIF when combined with INH. The Tmax decreased from 5.67 h to 3.3 h, and the
plasma concentration of RIF remained above its MIC (8 μg/ml) at all the tested time points starting with
15 min, when administered as RIF-SLNs in combination with INH.
Conclusion: The results confirm the scope of combining RIF-SLNs with INH to overcome the bioavailability
of free RIF when combined with INH, especially in fixed dose combinations.