In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery.

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 T max (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.

Potential of aerosolized rifampicin lipospheres for modulation of pulmonary pharmacokinetics and bio-distribution.

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.