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Öğe Application of HPLC to Investigate the Physicochemical Properties and Intestinal Permeability of Ketoprofen(Bentham Science Publ Ltd, 2017) Kaynak, Mustafa Sinan; Celebier, Mustafa; Akgeyik, Emrah; Sahin, Selma; Altinoz, SacideThe main objective of this study was to investigate the effect of pH on the solubility and intestinal permeability of ketoprofen by using HPLC. Ketoprofen is a slightly soluble acidic drug, and its solubility in aqueous phase is affected by pH changes dramatically. However, there is no data in the literature to support whether this pH dependent water solubility of ketoprofen will influence its absorption/bioavailability. In this study, the distribution-coefficient (log D) of ketoprofen at various pH values between 4.5 and 7.5 were investigated using HPLC, and then it was made an attempt to correlate the log D values with the intestinal permeability values. For this reason, in vivo intestinal permeability studies were performed at pH 4.5 and pH 7.5. The concentrations of model and reference compounds and also the blank buffers passed though the rat intestine were analyzed by means of a validated HPLC method. A nonlinear relationship was found between the results of in vitro and in vivo studies indicating that the diffusion of ketoprofen was not only related with passive diffusion, but also could be related with active transport.Öğe Determination of in vitro Dissolution Profiles of Amlodipine Besylate and Olmesartan Medoxomil Using a New HPLC Method(Chiminform Data S A, 2013) Kaynak, Mustafa Sinan; Celebier, Mustafa; Sahin, Selma; Altinoz, SpodeThe aim of this study was to develop an HPLC method for simultaneous determination of these active compounds and to apply this method to determine the dissolution of AML and OLM from a commercially available tablet. Valsartan (VAL) was used as an internal standard (IS). Separation of AML, OLM and VAL was performed using Phenomenex C-18 column (Luna 5 mu, 100A, 250x4.6 mm; California, USA) protected with a Phenomenex C-18 guard column (4.0x3.0 mm; California, USA). The chromatographic separation operated isocratically at room temperature using a mobile phase consisted of phosphate buffer (pH 4.0, 0.04 mol/L):methanol:acetonitrile (40:45:15, v/v/v) delivered at a flow rate of 0.8 mL/min and injection volume was 10 mu L. The diode array detector was set at 234 nm and 205 nm wavelengths for the quantification of AML and OLM respectively. In vitro dissolution studies revealed that 85% of the labeled amounts of AML and OLM were released within 25 min from their fixed combination tablet dosage form. The developed HPLC method was validated according to the ICH guidelines and it is proposed for dissolution studies of the combination dosage forms of these compounds.Öğe Determination of the Physicochemical Properties of Piroxicam(Turkish Pharmacists Assoc, 2020) Celebier, Mustafa; Nenni, Merve; Kaplan, Ozan; Akgeyik, Emrah; Kaynak, Mustafa Sinan; Sahin, SelmaObjectives: The aim of this study was to determine the acid dissociation constant (pKa) of piroxicam using high performance liquid chromatography (HPLC) and ultraviolet-visible (UV-Vis) spectrophotometry, and to determine the partition coefficient (Log P), distribution coefficient (Log D), and Log kw values of piroxicam using HPLC. Materials and Methods: The HPLC studies were performed on a reversed-phase ACE C18 (150x4.6 mm ID, 5 mu m) column at a flow rate of 1.0 mL min-1. The detector was set to 360 nm. Log D at different pH values (3.0-6.5) was examined with a phosphate buffer (20 mM) and acetonitrile (30:70 v/v) mixture as the mobile phase. For pKa determination, HPLC studies were performed with a mixture of phosphate buffer (20 mM) and methanol within the pH range of 3.50-6.00. Log kw measurements were performed with phosphate buffer (20 mM) and MeOH (from 20:80 v/v to 10:90 v/v) mixtures within the pH range of 3.50-6.00. UV-Vis spectrophotometric pKa measurements were performed at 285 nm wavelength. Results: The pKa value of piroxicam was found to be 5.3 by HPLC and 5.7 by UV-Vis spectrophotometry. Log P of piroxicam was determined as 1.58 in our experimental conditions. Log D values were 1.57, 1.57, 1.44, 1.13, and 0.46 for pH values of 3.17, 3.79, 4.44, 5.42, and 6.56, respectively. Conclusion: In the literature, different Log P (3.1, 2.2, and 0.6) and pKa (6.3 and 4.8) values were reported for piroxicam. The Log P (1.58) and pKa (5.3 and 5.7) values obtained for piroxicam in our study were within the range of the literature values. All these results indicate that different experimental approaches used for the determination of physicochemical properties could provide different values. Although UV spectrophotometry is easy to apply, HPLC is a unique technique for simultaneous determination of pKa, Log D, and Log P values of compounds.Öğe Development of HPLC Methods for Individual Determination of 20 Active Pharmaceutical Ingredients for Ussing-Chamber Studies(Bentham Science Publ Ltd, 2017) Kaynak, Mustafa Sinan; Akgeyik, Emrah; Ates, Muge; Celebier, Mustafa; Sahin, SelmaBackground: The aim of this study was to develop HPLC methods for individual determination of 20 active pharmaceutical ingredients (amoxicillin sodium, antipyrine, atenolol, caffeine, carbamazepine, cimetidine, enalapril, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, metoprolol tartrate, methyldopa, naproxen sodium, pindolol, piroxicam, propranolol HCl, ranitidine, theophylline, and verapamil HCl) to be used for determination of their intestinal permeabilities across Ussing-Chamber. Method: Two different stationary phases (Waters X-Bridge C18-150 x 4.6 mm, 5 mu m; and ACE 5 C18- 150 x 4.6 mm, 5 mu m) were used for the separation of the compounds. Three different aqueous phases (20 mM phosphate buffers pH 3.0, pH 6.0 and water) and two different organic phases (methanol and acetonitrile) were used to prepare the mobile phases. Total analysis time was shorter than 7 minutes for all applications. Result: The developed methods were validated according to the ICII guideline and found to be linear, sensitive, selective, precise and accurate. The developed methods could be applied for analyses of these compounds not only for Ussing-Chamber studies but also for other permeability studies.Öğe Evaluation of Pharmaceutical Quality of Conventional Dosage Forms Containing Paracetamol and Caffeine Available in the Turkish Drug Market(Dissolution Technologies, Inc, 2016) Akgeyik, Emrah; Kaynak, Mustafa Sinan; Celebier, Mustafa; Altinoz, Sacide; Sahin, SelmaThe aim of this study was to evaluate the quality of conventional paracetamol- (PA) and caffeine- (CA) containing combined dosage forms in the Turkish drug market. For this purpose, weight variation, content uniformity, diameter and thickness, hardness, friability, disintegration, and dissolution tests were carried out. Content uniformity and dissolution tests were performed by a validated high-performance liquid chromatography (HPLC) method. Separations were carried on an ACE 5-C-18, 5-mu m LC column (250 x 4.6 mm) using isocratic elution with a methanol/water (40:60 v/v) mobile phase. The injection volume was 20 mu L, and UV detection was performed at 270 nm. The weight variation results were in accordance with content uniformity results. All dosage forms fulfilled the USP requirement of not less than 75% of active ingredients of the labeled claim dissolved within 60 min. Also, all tablets met the rapidly dissolving criterion (more than 85% of the labeled amount of the drug substance dissolved within 30 min). The results of this study indicate that PA- and CA-containing conventional dosage forms available in the Turkish drug market pass all the established quality control tests successfully, and they can be used interchangeably.Öğe HPLC method development for the simultaneous analysis of amlodipine and valsartan in combined dosage forms and in vitro dissolution studies(Univ Sao Paulo, Conjunto Quimicas, 2010) Celebier, Mustafa; Kaynak, Mustafa Sinan; Altinoz, Sacide; Sahin, SelmaA simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C 18 column (ODS 2, 10 mu m, 200 x 4.6 mm) and a mobile phase of phosphate buffer (pH 3.6, 0.01 mol L-1): acetonitrile: methanol (46: 44: 10 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min(-1) and at ambient temperature. The injection volume was 20 mu L and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 -50 mu g mL(-1) for amlodipine, and 0.05 - 50 mu g mL(-1) for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.Öğe UV Spectrophotometric Method for Determination of the Dissolution Profile of Rivaroxaban(Dissolution Technologies, Inc, 2014) Celebier, Mustafa; Kaynak, Mustafa Sinan; Altinoz, Sacide; Sahin, SelmaRivaroxaban is an oral anticoagulant that is the first available orally active direct Factor Xa inhibitor. In this study, a UV spectrophotometric method was developed for the determination of rivaroxaban content in pharmaceutical formulations and the amount of rivaroxaban released in tablet dissolution studies. The dissolution profile of rivaroxaban was successfully determined with the validated method.