Formulation of nanocarriers for improvement of bioavailability of an antihypertensive drug : A pharmaceutical study / Maha Mohamed Abdullah Mahmoud ; Supervised Emad Basalious Besheir , Abeer Moustafa Khattab

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

Aliskiren- hemifumarate (AF) is non-peptide direct renin inhibitor used as antihypertensive drug. Renin is secreted by kidney and cleaves its substrate, angiotensinogen, forming the inactive decapeptide (Ang I) that is converted to an active octapeptide (Ang II) by angiotensin converting enzyme (ACE). Ang II is a powerful vasoconstrictor, enhances catecholamine release from adrenal medulla, and promotes aldosterone secretion and sodium reabsorption. All the currently available agents that inhibit the renin system stimulate compensatory renin release from the kidney, which results in an increase in plasma renin activity (PRA) that may ultimately lead to increased levels of Ang II, So targeting the renin system at its point of activation by directly inhibiting renin activity has therefore long been proposed as the optimal means of suppressing the renin system. Despite its potency as antihypertensive drug, its bioavailability is very poor (about 2.5%) which explained by its high solubility and poor permeability. Aliskiren is administered in market in a dose 150-300 mg but for high drug cost, the amount of drug in the prepared formulations ranged from 25-50 mg. The goal of this thesis is to enhance oral bioavailability of aliskiren.The work is divided into three chapters as follows: Chapter I: Preparation and Characterization of Aliskiren- loaded Transferosomal Vesicles Chapter II: Preparation and Characterization of Aliskiren- loaded Self Nanoemulsifying System (SNES) Chapter III: Preparation and Characterization of a SNENVS Formulation and Bioequivalence Study of the SNENVS Formulation and the Marketed Tablet

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