218 Evaluation bone uptake of alendronate sodium via vaginal route by gamma scintigraphy, Vaginal uptake of alendronate sodium D. Ilem-Ozdemir 1 *, M. Asikoglu 1 , T. Guneri 2 , K. Koseoglu 3 , H. Ozkilic 3 1 Department of Radiopharmacy, Faculty of Pharmacy, Ege University, 35100, Bornova, İzmir, Turkey 2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir, Turkey 3 Department of Nuclear Medicine, Faculty of Medicine, Ege University, 35100 Bornova, Izmir, Turkey *Correspondence: deryailem@gmail.com Alendronate sodium (ALD) is a second generation amino bisphosphonate that use for treatment of bone diseases. Since ALD is poorly absorbed from the gastrointestinal tract and its absorption is markedly reduced by food, the aim of this study is to evaluate the bone uptake of ALD through vaginal route. To evaluate the bone uptake of ALD by gamma scintigraphy, ALD was radiolabeled with Technetium-99m ( 99m Tc). Vaginal supposi- tories and injectable solution of 99m Tc-ALD was prepared and gamma scintigraphy studies were performed with intravaginally and intravenously 99m Tc-ALD applied rabbits. The results were revealed that ALD was successfully labeled with 99m Tc. After intravaginal and intravenous application, 99m Tc-ALD showed a high uptake in bone. Despite accumulation times and uptake ratios showed differences between administration routes, our preliminary observations suggest that the intravaginal route appears to be a viable alternative for ALD application and should be evaluated in future clinical studies. Key words: Alendronate sodium – Bone uptake – Gamma scintigraphy – Intravaginal application – Technetium-99m. J. DRUG DEL. SCI. TECH., 24 (2) 218-221 2014 Bisphosphonates (BPs) are stable analogs of pyrophosphates (P- O-P) and therapeutic agents for the treatment of bone diseases. They are strongly attracted to the bone where they inluence the calcium metabolism, mainly by inhibition of the osteoclast-mediated bone resorption [1, 2]. Bisphosphonates have been extensively applied in medicine, particularly in the ields of osteology, orthopedics and surgery. Over the past 12 years bisphosphonates have played a major role in the treatment of postmenopausal osteoporosis [1, 3]. The basic structure of bisphosphonates allows many possible variations, by changing the two lateral chains (R1-R2) on the carbon atom [4]. The various bisphosphonates are distinguished one from another by the ligands R1 and R2. Bisphosphonates are including ALD, etidronate, pamidronate, ibandronate, risedronate, clodronate, tiludronate, and zoledronate, which are variously used as the free acid or as the sodium salt [1]. ALD is a second generation amino bisphosphonates that selec- tively inhibits osteoclast-mediated bone resorption, increases bone mineral density and reduces the incidence of vertebral, hip and other fractures [5-7]. Like all bisphosphonates, ALD is poorly absorbed from the gastrointestinal tract, with an oral bioavailability of around 0.9-1.8 % [8]. Its absorption is markedly reduced by food [9]. The oral bioavailability of 10 mg ALD tablet, taken with plain water af- ter an overnight fast and 2 h before ingestion of the irst food of the day, is 0.8 % in woman. When the drug is taken 30 or 60 min before breakfast, its oral bioavailability is reduced to approximately 0.5 %. The drug’s bioavailability is reduced to approximately 0.3 % when ALD is taken with coffee or orange juice instead of plain water and negligible when taken up to 2 h after a standardized breakfast [10]. ALD is generally well tolerated. The most common adverse effect is upper gastrointestinal irritation, resulting in nausea, vomiting, abdominal pain, dyspepsia, esophagitis, and esophageal relux. Esophageal ulcers, stricture and erosion have also been reported [7, 11, 12]. It appears that a once weekly dosage with a large dose (70 mg) produces fewer gastrointestinal adverse effects than daily administration of a low dose [13]. To minimize adverse gastrointestinal effects, the tablets should be swallowed with a large glass of water; the patient should remain standing or seated upright and should not lie down for at least 30 min after eating [14, 15]. In recent years, there is a challenge for novel drug delivery sys- tems to achieve improved bioavailability and safety. Various methods have been used to improve the bioavailability of bisphosphonates are described. Because of the poor gastrointestinal (GI) absorption several administration routes have been attempted to enhance the bioavailability of bisphosphonates like intravenous, subcutaneous and intramuscular injections [16-19]. The vagina is an important area of the reproductive tract and serves as a potential route for drug administration. The anatomical position, the rich blood supply and the large surface area of the vagina predestines it as an application site for systemic drug delivery. Despite the fact that vaginal delivery is only available for females there are numbers of advantages like: the avoidance of hepatic irst-pass metabolism, decreasing of gastrointestinal and hepatic side effects. It overcomes the inconvenience caused by pain, tissue damage and probable infection by parenteral routes. Another advantage is the possible self-insertion and removal of the dosage form [20]. Gamma scintigraphy is one of the most popular methods to in- vestigate the GI performance of pharmaceutical dosage forms. This non-invasive technique gives information about integrity, dispersion or release characteristics of the radiolabeled delivery system. Choice of a suitable radionuclide for scintigraphic studies can be ascertained by considering factors such as the radiation energy, half-life, extent of particulate radiation, cost and availability. Technetium-99m ( 99m Tc) is the most popular radionuclide with its versatile chemistry, near-ideal energy (140 keV), low radiation dose and short half-life (6 h) [21, 22]. The purpose of the present study was to radiolabeled of ALD with 99m Tc, evaluate radiochemical purity and compare bone uptake of ALD which applied via vaginal and intravenous route in rabbits. Vaginal application potential of ALD was evaluated. I. MATERIALS AND METHODS 1. Materials ALD was obtained as a gift from Arylsa Company. 99m Tc-sodium pertechnetate was obtained from Department of Nuclear Medicine of Ege University. Stannous chloride (Sigma) was used as reducing agent and ascorbic acid (Roche) was used as an antioxidant in labe-