title: Novel rifampicin-phospholipid complex for tubercular therapy: synthesis, physicochemical characterization and in-vivo evaluation.
abstract: 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. 48.5 μg/mL), increased AUC0-∞ (472.4 vs. 147.71 5.812 ± 0.49 μg h/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.
authors.affiliation: Department of Pharmaceutical Technology (Formulation), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab 160062, India.
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.affiliation: Technology Development Centre, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab 160062, India.
authors.forename: Tara Datt
authors.initials: TD
authors.lastname: Bhatt
authors.affiliation: Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab 160062, India.
authors.forename: Manjinder Singh
authors.initials: MS
authors.lastname: Gill
authors.affiliation: Department of Pharmaceutical Technology (Formulation), National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), Punjab 160062, India. Electronic address: ssuresh@niper.ac.in.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D000904:Antibiotics, Antitubercular / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D008297:Male; D008855:Microscopy, Electron, Scanning; D010743:Phospholipids / Q000737:chemistry* / Q000493:pharmacokinetics*; D033362:Powder Diffraction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D000904:Antibiotics, Antitubercular; D010743:Phospholipids; D012293:Rifampin
keywords: Oral bioavailability; Pharmacokinetic; Rifampicin; Rifampicin–phospholipid complex