Novel rifampicin–phospholipid complex for tubercular therapy: Synthesis, physicochemical characterization and in-vivo evaluation

• Published in: International journal of pharmaceutics Vol. 460; no. 1-2; pp. 220 - 227
• Main Authors: Singh, Charan, Bhatt, Tara Datt, Gill, Manjinder Singh, Suresh, Sarasija
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 02-01-2014
• Subjects: Animals; Antibiotics, Antitubercular - blood; Antibiotics, Antitubercular - chemistry; Antibiotics, Antitubercular - pharmacokinetics; Biological Availability; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Drug Stability; Male; Microscopy, Electron, Scanning; Oral bioavailability; Pharmacokinetic; Phospholipids - chemistry; Phospholipids - pharmacokinetics; Powder Diffraction; Rats; Rats, Sprague-Dawley; Rifampicin; Rifampicin–phospholipid complex; Rifampin - blood; Rifampin - chemistry; Rifampin - pharmacokinetics; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; Rifampicin–phospholipid complex; Oral bioavailability; Rifampicin; Pharmacokinetic
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.10.043

To enhance the oral bioavailability of rifampicin (RMP), the newly emerging phospholipid complexation technique was employed. Rifampicin–phospholipid complex (RMP-PC) was prepared by solvent-evaporation method. Infrared spectroscopy (IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and hot stage microscopy (HSM) analysis were employed to confirm the formation of phospholipid complex. The results reveal hydrogen bond formation and electrostatic interaction between RMP and phospholipid molecule play an important role in the formation of RMP-PC without the formation of a new compound. In comparison with the physical mixture and RMP, solubility studies indicated an enhancement in the aqueous solubility of RMP-PC. Stability studies of RMP-PC in presence of isoniazid showed a remarkable improvement of the stability of the phospholipid complex in comparison to free RMP. Oral bioavailability of RMP-PC was evaluated in Sprague-Dawley (SD) rats and plasma rifampicin estimated by LCMS. RMP-PC exhibited higher peak plasma concentration (54.3 vs. 48.5μg/mL), increased AUC0–∞ (472.4 vs. 147.71 5.812±0.49μgh/mL), increased T1/2 (8.3 vs. 1.5h) when compared to free RMP implying improved bioavailability of the drug. This enhancement can be attributed to the improvement of the aqueous solubility of rifampicin–phospholipid complex. Hence, phospholipid complexation holds a promising potential for increasing oral bioavailability of poorly water soluble drugs.