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Papers by Makbule Asikoglu

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of o... more 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 (99mTc) by direct method. The radiochemical characterization of the 99mTc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of 99mTc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing 99mTc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The 99mTc-labeled ALD suppositories were admin...

The aim of the present study is to evaluate doxycycline hyclate biodistribution by gamma scintigr... more The aim of the present study is to evaluate doxycycline hyclate biodistribution by gamma scintigraphy in inflamed rats. The Technetium-99m ( 99m Tc) eluted was used for labeling of doxycycline hyclate. 99m Tc-doxycycline hyclate was prepared with a radiochemical yield greater than 90%, adding 99m Tc to doxycycline hyclate in the presence of stannous tartarate and ascorbic acid. Scintigraphic studies in rats were carried out using experimentally induced inflammation in the left thigh muscle using turpentine oil. Static images were acquired by a gamma camera in different time intervals for 6 hours. For quantitative evaluation of 99m Tc-doxycycline hyclate uptake, the regions of interest were drawn around and uptakes were calculated as counts per pixel. According to in vivo studies, the accumulation of 99m Tc-doxycycline hyclate in the inflamed muscle was found higher than the control muscle.

Asikoglu et al. have demonstrated rectal absorption of ALD (14).

Die Pharmazie, 2011

The work aims to confirm the complexation of albendazole (ABZ) by beta-cyclodextrin (beta-CD), an... more The work aims to confirm the complexation of albendazole (ABZ) by beta-cyclodextrin (beta-CD), and to compare them with pure ABZ tablets using radioactive and nonradioactive dissolution studies. The complex tablets were prepared by kneading a binary mixture of ABZ and beta-CD and a direct compression method. Nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were examined to prove the formation of complexes in the final products. The radiolabelled tablets were labelled with 99mTc-DTPA. Dissolution studies were performed with radiolabelled and nonradiolabelled tablets in two dissolution media (pH 1.2 and pH 7.4). The tablets were added to an acidic solution (pH = 1.2) to quantify the concentration of the drug inside the beta-CD cavity. The other medium (pH = 7.4) was used to prove the existence of non-complexed drug in each powder, as the drug's solubility increases with pH. It was observed that com...

Drug Development and Industrial Pharmacy, 2014

Abstract The purpose of this work is to prepare a self-microemulsifying drug delivery system (SME... more Abstract The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value. In vitro Caco-2 cell permeability studies were performed for SMEDDS and solution of radioactive ((99 m)Tc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD.

Bisphosphonates can be labeled with Techne

Pharmaceutical Development and Technology, 2008

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of o... more 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.

Journal of Radioanalytical and Nuclear Chemistry, 2013

ABSTRACT Since radiolabeled antibiotics specifically bind to the bacterial components they are pr... more ABSTRACT Since radiolabeled antibiotics specifically bind to the bacterial components they are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline hyclate (DOX) was chosen to investigate as a new radiolabeled antibacterial agent since its bacteriostatic activity against a wide variety of microorganisms. The aim of the present study is to develop simple and easy formulation of DOX with 99mTc ready to use kit. 99mTc-DOX was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose and reducing agent type. Labeling studies were performed by changing the selected parameters one by one and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Radiochemical purity was determined with RTLC and RHPLC which was found more than >95 %. Two different freeze dry kits were formulated with optimum labeling conditions. The improved kits were found stable up to 6 months.

Journal of Pharmacy and Pharmacology, 1995

The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied ... more The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In-vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. In the physicochemical investigations the pH indicators (pH 1-14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37 degrees C for 3 days, then the diameters of inhibition zones were measured. In the dissolution investigations release rates were in the order PEG 6000 > PEG 4000 > PEG 1500 > > Witepsol H15 > Cremao > Novata BD. The diffusion distance of isoconazole nitrate in the physicochemical investigation was in the order polyethylene glycols > Witepsol H15 > Novata BD. In the microbiological studies release rates were found with polyethylene glycols > Witepsol H15 > Novata BD > Cremao. The findings in the in-vitro studies suggested that polyethylene glycols are suitable bases for vaginal suppositories.

Journal of Labelled Compounds and Radiopharmaceuticals, 2014

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detecti... more Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new 99m Tc-labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by 99m Tc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen-free, and stable up to 6 months.

Journal of Radioanalytical and Nuclear Chemistry, 2015

In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy fo... more In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, 99m Tc-MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since 99m Tc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients.

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of o... more 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 (99mTc) by direct method. The radiochemical characterization of the 99mTc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of 99mTc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing 99mTc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The 99mTc-labeled ALD suppositories were admin...

The aim of the present study is to evaluate doxycycline hyclate biodistribution by gamma scintigr... more The aim of the present study is to evaluate doxycycline hyclate biodistribution by gamma scintigraphy in inflamed rats. The Technetium-99m ( 99m Tc) eluted was used for labeling of doxycycline hyclate. 99m Tc-doxycycline hyclate was prepared with a radiochemical yield greater than 90%, adding 99m Tc to doxycycline hyclate in the presence of stannous tartarate and ascorbic acid. Scintigraphic studies in rats were carried out using experimentally induced inflammation in the left thigh muscle using turpentine oil. Static images were acquired by a gamma camera in different time intervals for 6 hours. For quantitative evaluation of 99m Tc-doxycycline hyclate uptake, the regions of interest were drawn around and uptakes were calculated as counts per pixel. According to in vivo studies, the accumulation of 99m Tc-doxycycline hyclate in the inflamed muscle was found higher than the control muscle.

Asikoglu et al. have demonstrated rectal absorption of ALD (14).

Die Pharmazie, 2011

The work aims to confirm the complexation of albendazole (ABZ) by beta-cyclodextrin (beta-CD), an... more The work aims to confirm the complexation of albendazole (ABZ) by beta-cyclodextrin (beta-CD), and to compare them with pure ABZ tablets using radioactive and nonradioactive dissolution studies. The complex tablets were prepared by kneading a binary mixture of ABZ and beta-CD and a direct compression method. Nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were examined to prove the formation of complexes in the final products. The radiolabelled tablets were labelled with 99mTc-DTPA. Dissolution studies were performed with radiolabelled and nonradiolabelled tablets in two dissolution media (pH 1.2 and pH 7.4). The tablets were added to an acidic solution (pH = 1.2) to quantify the concentration of the drug inside the beta-CD cavity. The other medium (pH = 7.4) was used to prove the existence of non-complexed drug in each powder, as the drug's solubility increases with pH. It was observed that com...

Drug Development and Industrial Pharmacy, 2014

Abstract The purpose of this work is to prepare a self-microemulsifying drug delivery system (SME... more Abstract The purpose of this work is to prepare a self-microemulsifying drug delivery system (SMEDDS) for risedronate sodium (RSD) and to compare the permeability with RSD solution. The solubility of RSD was determined in different vehicles. Phase diagrams were constructed to determine the optimum concentration of oil, surfactant, and cosurfactant. RSD SMEDDS was prepared by using a mixture of soybean oil, cremophor EL, span 80, and transcutol (2.02:7.72:23.27:61.74, w/w, respectively). The prepared RSD SMEDDS was characterized by droplet size value. In vitro Caco-2 cell permeability studies were performed for SMEDDS and solution of radioactive ((99 m)Tc-labeled RSD) and nonradioactive RSD. The experimental results indicated that RSD SMEDDS has good stability and its droplet size is between 216.68 ± 3.79 and 225.26 ± 7.65 during stability time. In addition, RSD SMEDDS has higher permeability value than the RSD solution for both radioactive and nonradioactive experiments. The results illustrated the potential use of SMEDDS for delivery of poorly absorbed RSD.

Bisphosphonates can be labeled with Techne

Pharmaceutical Development and Technology, 2008

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of o... more 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.

Journal of Radioanalytical and Nuclear Chemistry, 2013

ABSTRACT Since radiolabeled antibiotics specifically bind to the bacterial components they are pr... more ABSTRACT Since radiolabeled antibiotics specifically bind to the bacterial components they are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline hyclate (DOX) was chosen to investigate as a new radiolabeled antibacterial agent since its bacteriostatic activity against a wide variety of microorganisms. The aim of the present study is to develop simple and easy formulation of DOX with 99mTc ready to use kit. 99mTc-DOX was developed and standardized under varying conditions of reducing and antioxidant agent concentration, pH, radioactivity dose and reducing agent type. Labeling studies were performed by changing the selected parameters one by one and optimum labeling conditions were determined. After observing the conditions for maximum labeling efficiency and stability, lyophilized freeze dry kits were prepared accordingly. Radiochemical purity was determined with RTLC and RHPLC which was found more than >95 %. Two different freeze dry kits were formulated with optimum labeling conditions. The improved kits were found stable up to 6 months.

Journal of Pharmacy and Pharmacology, 1995

The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied ... more The influence of the suppository base on the in-vitro release of isoconazole nitrate was studied by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. Vaginal suppository formulations containing 25 mg isoconazole nitrate for local treatment of vaginitis were prepared by a fusion method, using different hydrophilic and lypophilic suppository bases (PEG 6000, PEG 4000, PEG 1500, Witepsol H15, Novata BD and Cremao). In-vitro release rates were examined by dissolution, physicochemical diffusion and microbiological disk-diffusion methods. In the physicochemical investigations the pH indicators (pH 1-14) erythrosin B, thymol blue, bromocresol green, chlorophenol red, phenol red, and alkali blue were added to agar gels. The discs were placed onto the agar gels and 21 h later, the coloured zone diameters were measured. In the microbiological investigations, the discs were put on the inoculated plates with the suspension of Candida albicans (Institute Pasteur 628). The inoculated plates were incubated at 37 degrees C for 3 days, then the diameters of inhibition zones were measured. In the dissolution investigations release rates were in the order PEG 6000 > PEG 4000 > PEG 1500 > > Witepsol H15 > Cremao > Novata BD. The diffusion distance of isoconazole nitrate in the physicochemical investigation was in the order polyethylene glycols > Witepsol H15 > Novata BD. In the microbiological studies release rates were found with polyethylene glycols > Witepsol H15 > Novata BD > Cremao. The findings in the in-vitro studies suggested that polyethylene glycols are suitable bases for vaginal suppositories.

Journal of Labelled Compounds and Radiopharmaceuticals, 2014

Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detecti... more Radiolabeled antibiotics are promising radiopharmaceuticals for the precise diagnosis and detection of infectious lesions. Doxycycline Hyclate (DOX) was chosen to investigate new 99m Tc-labeled antibacterial agent. Ready to use freeze dry kits were formulated with optimum labeling conditions. Human serum stability, sterility, and pyrogenicity of kits were estimated, and gamma scintigraphy, in vivo biodistribution, and histopathological studies with bacterial infected rats were performed. DOX were successfully labeled by 99m Tc with high radiochemical purity, and the labeled compound was stable in human serum. Kits were sterile, pyrogen-free, and stable up to 6 months.

Journal of Radioanalytical and Nuclear Chemistry, 2015

In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy fo... more In the present study 99m Tc-MTX was prepared with high labeling yield by a new simple and easy formulation method. According to cell culture studies, 99m Tc-MTX incorporated with both MCF-7 and CRL8798 cells, with significant differences in the uptake percentages. Since 99m Tc-MTX highly uptake in cancer cell line, the results demonstrated that radiolabeled MTX may be promising for breast cancer diagnosis of oncological patients.