The absorption of (99m)Tc-alendronate given by rectal route in rabbits.

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%-1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m ((99m)Tc) by direct method. The radiochemical characterization of the (99m)Tc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of (99m)Tc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing (99m)Tc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The (99m)Tc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of (99m)Tc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

W/O/W multiple emulsions containing nitroimidazole derivates for vaginal delivery.

The aim of our study was to formulate a stable multiple emulsions containing two nitroimidazole derivates, metronidazole (MT) and ornidazole (OR), for vaginal therapy. MT and OR were located internal and external phases of multiple emulsion, respectively, and the in vitro release studies were realized in phosphate (pH 7) and lactate buffer (pH 4.5) solutions to investigate better the effect of pH and location of active substance on the release. The imaging studies were realized in rabbits following labeling MT and OR with Technethium-99m ((99m)Tc) to evaluate the in vivo absorption characteristics. The percentage of MT and OR released from the multiple emulsions in alkaline media were 3.2- and 2.8-fold greater than that observed in acidic media, respectively, when they were introduced in the internal phase of the multiple emulsions. The absorption rate of MT from vaginal epithelium was faster than OR. We observed that especially in alkaline medium a high release was found that was convenient for the vaginal infections seen in the alkaline pH. We concluded that W/O/W multiple emulsions were locally effective in vagina and they could be introduced as a new drug carrier system for vaginal delivery.

In-vitro evaluation and vaginal absorption of metronidazole suppositories in rabbits.

Vaginal suppository formulations of metronidazole were prepared using six different bases as Witepsol H15, Cremao, Ovucire WL2944, Ovucire WL3264, PEG 1500, PEG 6000. Three different dissolution methods were used to evaluate the in vitro drug release from the suppositories. The diffusion studies were performed through synthetic (cellophane) and natural membrane (rabbit vagina), but the drug did not show good permeation characteristics from natural membrane. Ovucire WL3264 suppositories of metronidazole labeled with 99mTc (Tecnetium-99m) were used for the vaginal absorption and biodistribution studies in the rabbits. Scintigraphic images were collected after vaginal administration of the labeled suppositories using SPECT gamma fitted with a low energy, high-resolution parallel hole collimator. The labeled drug showed high biodistribution in urine beside vaginal site. The results of this study suggested that the Ovucire WL3264 suppository of metronidazole prepared for vaginal infections could also be effective in the urinary infections.