Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Optimized drug administration allows the delivery of the drug to the correct location and provides an effective concentration for the required length of time, thereby achieving the therapeutic objective with minimal side effects. The challenge lies in manipulating the formulation to produce a release rate which is appropriate for the pharmacokinetic properties of the drug; resulting in a concentration-time profile at the site of action that will meet the pharmacological requirements. This must be fulfilled in a product that will be readily accepted by the patient, otherwise non-compliance will result in drug delivery failure. Bosentan is a drug belonging to endothelin receptor antagonist (ERA) that can be used for pulmonary arterial hypertension. It is available in two concentrations 62.5 mg and 125 mg twice daily. Bosentan is a poorly water soluble drug. The oral delivery of bosentan suffers from several drawbacks such as low bioavailability (absolute bioavailability 50%), short duration of action necessitating frequent administration and systemic hypotension. The main side effects include headache, flushing and increased liver enzymes. Pulmonary administration would circumvent the pre-systemic hepatic metabolism thus improving the bioavailability of bosentan. Moreover, the direct delivery to the lung avoids the systemic adverse effects of oral ERA. However, the short duration of action and the frequent administration are the major drawbacks of inhalation therapy

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