Evaluation of antitubercular drug‐loaded surfactants as inhalable drug‐delivery systems for pulmonary tuberculosis

Abstract Pulmonary tuberculosis is associated with a year‐long chemotherapy, poor alveolar drug levels, drug‐related systemic toxicity, and patient noncompliance. In this study, exogenous pulmonary surfactant is proposed as a drug carrier for antitubercular drugs. Dipalmitoylphosphatidylcholine (DPPC), the major lung‐surfactant lipid, has been combined with antitubercular drugs isoniazid (INH), rifampicin (RFM), and ethambutol (ETH) in 1:1 ratio by weight, in which drugs had a ratio of 1:2:3 by weight. At 37°C, the formulation had better surfactant function with quicker reduction of surface tension on adsorption (32.71 ± 0.65 mN/m) than DPPC liposomes (44.67 ± 0.57 mN/m) and maintained 100% airway patency in a capillary surfactometer. Drug‐loaded surfactant liposomes were about 2 μm and had entrapment efficiency of 30.04% ± 2.05%, 18.85% ± 2.92%, and 61.47% ± 3.32% for INH, RFM, and ETH, respectively. Sustained release of the drugs from surfactants was observed over 24 h. In vitro alveolar deposition efficiency using the twin impinger showed 12.06% ± 1.87% of INH, 43.30% ± 0.87% of RFM, and 22.07% ± 2.02% of ETH deposited in the alveolar chamber upon nebulization for a minute using a jet nebulizer. The formulation was biocompatible and stable with physicochemical properties being retained even after storage for a month at 4°C. Antitubercular drug‐loaded surfactants developed could serve dual purposes of alveolar stabilization due to surfactant action and better reach of these drugs to the alveoli due to antiatelectatic effect of the surfactant. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009