Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Bronchial asthma is a widespread chronic respiratory inflammatory disease characterized by coughing, shortness of breath, chest tightness and wheezing. Inhaled corticosteroids (ICSs) are still the brilliant treatment that can successfully stifle the characteristic aggravation in asthmatic airways. Despite their advantageous clinical impacts, their long-term treatment is associated with some notable complications that motivate developing a novel inhaled glucocorticoid with high local potency and negligible systemic absorption to improve safety profile.Ciclesonide (CIC) has been approved for the treatment of asthma. It is a is non-halogenated glucocorticosteroid of new generation with high local anti- inflammatory properties and no oral bioavailability. CIC is an inactive prodrug that is converted in lung tissue to its active metabolite, desisobutyryl-ciclesonide (des- CIC) by esterase enzyme found in airways. Des-CIC has a 100-fold relatively higher glucocorticoid receptor binding affinity than CIC which has practically no affinity for this receptor.CIC is currently accessible as metered dose inhaler (MDI) which has a major challenge in the management of the elderly, critically ill patients and children. The use of ethanol as co-solvent to improve the poor solubility of CIC in hydrofluroalkane (HFA) propellant used in the commercial product is another critical concern where, reduction in the formulation vapors pressure required for automation upon ethanol addition was reported with consequent increase in mass median aerodynamic diameter (MMAD) with a decrease in fine particle fraction (FPF) that inevitably impair system performance and decrease delivered CIC to the lung

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