title: Potential of aerosolized rifampicin lipospheres for modulation of pulmonary pharmacokinetics and bio-distribution.
abstract: The aim of the present study was to establish the potential of rifampicin loaded phospholipid lipospheres carrier for pulmonary application. Lipospheres were prepared with rifampicin and phospholipid in the ratio of 1:1 using spray drying method. Further, lipospheres were evaluated for flow properties and surface area measurement. The formulated lipospheres were evaluated in vitro for aerodynamic characterization and in vivo for lung pharmacokinetics and biodistribution studies in Sprague Dawley rats. Powder flow properties finding suggested the free flowing nature of the lipospheres. In-vitro aerosol performance study indicated more than 80±5% of the emitted dose (ED) and 77.61±3% fine particles fraction (FPF). Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were found to be 2.72±0.13 μm and 3.28±0.12, respectively. In-vitro aerosol performance study revealed the higher deposition at 3, 4 and 5 stages which simulates the trachea-primary bronchus, secondary and terminal bronchus of the human lung, respectively. The drug concentration from nebulized lipospheres in the non-targeted tissues was lesser than from rifampicin-aqueous solution. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 8.03 for lipospheres as compared to rifampicin-aqueous solution. Thus, the results of the study demonstrated the potential of rifampicin lipospheres formulation would be of use as an alternative to existing oral therapy.
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: 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: L V Seshu Kumar
authors.initials: LV
authors.lastname: Koduri
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Dhawale
authors.affiliation: Technology Development Center, 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: Central Instrumentation Laboratory, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
authors.forename: Rajdeo
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Central Instrumentation Laboratory, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Grover
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India.
authors.forename: Kulbhushan
authors.initials: K
authors.lastname: Tikoo
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: sarasija_s@hotmail.com.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D008168:Lung / Q000378:metabolism; D008297:Male; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D000904:Antibiotics, Antitubercular; D004337:Drug Carriers; D010743:Phospholipids; D011208:Powders; D012293:Rifampin
keywords: Cascade impactor; Lipospheres; Powder characterization; Pulmonary pharmacokinetic; Rifampicin