Development of a Carrier Free Dry Powder Inhalation Formulation of Ketotifen for Pulmonary Drug Delivery.

BACKGROUND: Pulmonary drug delivery route is gaining much attention because it enables to target the active ingredients directly to lung both for local and systemic treatments, which maximize the therapeutic effect and minimize unwanted systemic toxicity. Dry powder inhaler (DPI) systems for asthma therapy have shown several merits to the other pulmonary delivery systems such as nebulizers and metered dose inhalers. PURPOSE: The present study aims to develop and optimize a DPI formulation for Ketotifen fumarate through spray drying technique. METHODS: Particles size and morphology, crystallinity, and drug-excipient interaction of fabricated DPI formulations were evaluated by scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier Transform Infrared Spectroscopy methods, respectively. The aerosolization indexes and aerodynamic properties of dry powders were determined by next generation impactor. The powder flowability was assessed by measuring the Hausner ratio and compressibility index. RESULTS: Among solvent systems, ethanol-water mixture produced the most desirable powder property for inhalation after spray drying. Although co-spray dried formulations with ammonium bicarbonate resulted in the porous structure, it was not beneficial for DPI formulations due to the interaction with Ketotifen. DSC and XRD experiments proved the amorphous structure of prepared powders, which were stable for 12 months. CONCLUSION: The results of this study demonstrate the potential of Ketotifen DPI formulation and pave a way to use it easily in an industrial scale.

Formulation of Menthol-Loaded Nanostructured Lipid Carriers to Enhance Its Antimicrobial Activity for Food Preservation.

Purpose: Due to the antimicrobial property, menthol have significant potential for food preservation and foodstuff shelf life improvement. Nevertheless, menthol instability, insolubility, and rapid crystallization in aqueous media make it unsuitable for used in food products. This work was aimed to prepare menthol-loaded nanostructured lipid carriers (NLCs) to enhance its antimicrobial activity. Methods: Morphology, particle size and size distribution, encapsulation efficiency percent (EE%), and physical stability of the optimized formulation, prepared by hot melt homogenization method, were characterized by scanning electron microscopy, particle size analyzing, gas chromatography, and X-ray diffraction (XRD) methods. Minimum inhibitory concentration and minimum bactericidal concentration of menthol-loaded NLCs were evaluated and compared with conventional menthol emulsion against various Gram-positive (Staphylococcus aureus, Bacillus cereus) and Gram-negative bacteria (Escherichia coli), as well as one fungus (Candida albicans). Results: Menthol-loaded NLCs were spherically shaped nanosized (115.6 nm) particles with narrow size distribution (PDI = 0.2), suitable menthol EE% (98.73%), and appropriate physical stability after 90 days of storage period. XRD results indicated that menthol was in the amorphous form in the nanoparticles matrix. Antibacterial assay results revealed that the menthol-loaded NLCs exhibited significantly higher in vitro antimicrobial property than conventional menthol emulsion. The results also indicated that menthol-loaded NLCs had better effect on fungi than bacteria, and furthermore, antibacterial efficiency on Gram-positive bacteria was higher than Gram-negative bacteria. Conclusion: In conclusion, NLCs could be a promising carrier for improvement of antimicrobial activity and preservation efficacy of essential oils in foodstuffs.