Dry powder inhalation of liposomal Ketotifen fumarate: formulation and characterization

The purpose of the experiment was to formulate and characterize the dry pow der inhalation (DPI) formulation of liposomally entrapped anti-asthmatic dr ug, Ketotifen. fumarate (KF). Liposomes composed of saturated egg phosphati dyl choline (EPC) and cholesterol (CHOL) were prepared by lipid film hydrat ion and sonicated to have the desired size ( < 5 <mu>m). Process variable s uch as vacuum, presonication hydration, postsonication hydration, purificat ion and lamellae composition, were optimized for encapsulation efficiency o f KF. Liposomal dispersion was blended with cryoprotectant (sugar) in varyi ng bulk and mass ratios and assessed for its influence on retention of enca psulated drug on lyophilization. Characterization of liposomal dispersion w as done for size, lamellarity, entrapped volume and oxidation index. DPI fo rmulation was characterized for angle of repose, compressibility index, dis persibility and respirable fraction (British Pharmacopoeia, apparatus A). P rocess optimization revealed that a vacuum, 20 in.; presonication hydration , 60 min; postsonication hydration, 2 h and purification by dialysis gave m aximum encapsulation efficiency. Sucrose was found to be the most suitable cryoprotectant at bulk strength of 500 mM and mass ratio of lipid/sugar, 1/ 12. Blending of sorbolac before lyophilization showed better retention of e ncapsulated KF (97.92 +/-0.54%). In the preparation of sonicated MLVs, the presence of nitrogen atmosphere, alpha -tocopherol and EDTA could not total ly eliminate EPC oxidation, expressed as the change in oxidation index from 0.427 +/-0.01 to 1.510 +/-0.01. The respirable fraction of the developed f ormulation (21.59 +/-1.53%) is comparable with the control (26.49 +/-1.52%) . From studies, it may be concluded that an optimal bulk and mass ratio of sucrose, relative to the size of liposomes is necessary for effective cryop rotection. In this investigation, DPI of liposomal KF was successfully prep ared and delivered to the required site in the lungs. (C) 2001 Elsevier Sci ence B.V. All rights reserved.