INHALED TASTE MASKED SPRAY DRIED KETOTIFEN MICROPARTICLES: FORMULATION, CHARACTERIZATION AND IN VITRO PULMONARY DEPOSITION
Objective: Preparation and characterization of inhalable taste masked microparticles (MPs) loaded with the anti-asthmatic bitter drug, ketotifen (KT).
Methods: MPs were prepared by a spray-drying technique. The effects of addition of different excipients namely: mannitol, leucine and hyaluronic acid (HA) on the physicochemical properties of KT spray dried powders were determined. Powder taste was evaluated on volunteers. DSC and x-ray diffraction were done to investigate thermal and crystallographic properties of the powders. The surface morphology and shape of KT-loaded hyaluronic acid MPs were examined using scanning electron microscope, in vitro pulmonary deposition and inhalation indices were determined using a twin stage glass impinger (TSI).
Results: Leucine improved the powder flow properties. Mannitol, at all tested ratios, produced brownish discoloration in spray dried powders (SDP) upon storage even in dessicator. At a drug to HA ratio of 1:2, the bitter taste of KT had significantly improved besides obtaining a high respirable particle fraction. This selected ratio showed good physicochemical stability for up to 9 mo.
Conclusion: The developed KT spray dried particles may offer a good platform for the targeted pulmonary delivery of the drug overcoming the major biological barriers.
Keywords: Ketotifen, Microparticles, Pulmonary delivery, Hyaluronic acid, Taste masking, Spray drying
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