Utilization of nanotechnology in enhancing the bioavailability of one of a BCS class II drugs / Eman Abdelrasheed Ghanem ; Supervised Salwa Mohamed Salah , Rania Hassan Fahmy , Manal M. Elashmoony

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

Raloxifene hydrochloride (RLX) belongs to the benzothiophene class of compounds where its biological action is brought about by binding to estrogen receptors (ERs). Such binding leads to the activation of some estrogenic receptors and the blockage of others. This agonist/antagonist action is commonly known as a selective estrogen receptor modulator (SERM). It acts as an agonist on bone and cholesterol metabolism (decrease in total and LDL-cholesterol), but not in the hypothalamus, in the uterine nor the breast tissues.In the premenopausal stage, RLX reduces bone resorption and biochemical markers of bone turnover. Hence, this leads to an increase in bone mineral density (BMD) and a decrease in fractures occurrence. Moreover, in-vitro studies showed that RLX inhibits the estradiol dependent proliferation of human mammary tumor cells.Thus, RLX prevents and treats osteoporosis and reduces invasive breast cancer development in postmenopausal women. It should be noted that the drug indication mandates long term therapy that is why when determining the choice of therapy, menopausal signs, effects on uterine and breast organs, and cardiovascular risks and benefits should all be taken into account.Consequently, RLX is the mainstay therapy for osteoporosis, concurrently with bisphosphonates. A major critical factor is the low absolute bioavailability (2 %) of RLX which is correlated to its poor aqueous solubility (biopharmaceutics classification system-BCS class II) in addition to the extensive first pass metabolism (even though rapidly absorbed after oral administration; approximately 60 %)

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