title: In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery.
abstract: The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 ± 23 versus 105.1 ± 12 μg/ml and SDRPL (1:1) 306.4 ± 20 versus 105.1 ± 12 μg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 ± 25 versus 54.31 ± 18 μg/ml), faster Tmax(two versus four hours), and enhanced area under the curve (AUC0-∞) (406.92 ± 18 versus 147.72 ± 15 μg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin.
authors.affiliation: Department of Pharmaceutical Technology (Formulation), Mohali, India.
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Technology (Formulation), Mohali, India.
authors.forename: L V Seshu Kumar
authors.initials: LV
authors.lastname: Koduri
authors.affiliation: Technology Development Center, Mohali, India.
authors.forename: Tara Datt
authors.initials: TD
authors.lastname: Bhatt
authors.affiliation: Common Biological Testing Laboratory, Mohali, India.
authors.forename: Sarbjit Singh
authors.initials: SS
authors.lastname: Jhamb
authors.affiliation: Common Biological Testing Laboratory, Mohali, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Technology Development Center, Mohali, India.
authors.forename: Manjinder Singh
authors.initials: MS
authors.lastname: Gill
authors.affiliation: Department of Pharmaceutical Technology (Formulation), Mohali, India. sarasija_s@hotmail.com.|National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India. sarasija_s@hotmail.com.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D008297:Male; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D000904:Antibiotics, Antitubercular; D010743:Phospholipids; D012293:Rifampin
keywords: Mycobacterium tuberculosis; antimycobacterial activity; bioavailability; carrier system; lipospheres; pharmacokinetic; rifampicin; solid state; solubility