Iranian Journal of Pharmaceutical Sciences

Glipizide has been found to form inclusion complexes with β-cyclodextrin (β-CD) in solution and in solid state. The present study was undertaken to determine a suitable method for scaling up glipizide-β-CD inclusion complex formation and to evaluate the effect of some parameters on the efficiency of complexation. The solid inclusion complexes of glipizide and β-CD were prepared at a molar ratio of 1:1 and 1:2 by mixing, kneading, and co-precipitation methods both on small and large scales. The effect of parameters such as kneading time and temperature on complexation was also studied. Characterization was performed using infrared spectroscopy, X-ray diffractometry, and dissolution studies. In vitrorelease studies were carried out in phosphate buffer (pH 7.4). All the methods of preparation of complexes were found to be useful in increasing the solubility of glipizide except mixing method where the rise in solubility was not significant. Both kneading and co-precipitation methods in 1:2 molar ratios were found to be equally effective inimproving the solubility of glipizide. The formation of inclusion complexes was evident in these formulations as shown by IR and XRD studies. But when carried out on a large scale, co-precipitation method was found to be more tedious and time-consuming than kneading method. Moreover percent recovery of complexes in the kneading method was found to be 98.76% as compared to 92.05% in case of co-precipitation method. Drug content studies, IR spectroscopic studies, X-ray diffractometry studies andin vitrodissolution study data indicated that inclusion complexes prepared by kneading method in 1:2 molar ratios were suitable for improving the solubility of glipizide. The same formulation was prepared at large scale and optimum formulation conditions were established.

Cyproterone acetate (CA) has been loaded to liposome by solvent evaporation and thin film formation technique. The effects of some formulation variables such as temperature of organic solvent evaporation, rotary evaporator speed, volume of organic solvent, volume of balloon and temperature of hydrating buffer has been evaluated. The data showed that bigger balloon with higher surface area has better capacity for lipidic film formation; also the best temperature for solvent evaporation and film hydration was 40 °C. According to the data with higher drug/lipid ratio,it is possible to load higher amount of drug into liposome but optimum loading could be obtained at phosphatidylcholine (PC): cholesterol/drug ratio of 1:2:0.5 (with maximum 74±6.11% loading efficiency). Finally percutaneous absorption of CA from simple gel and liposomal formulations was assessed. The results showed that liposomal formulation has better penetration potential than conventional CAformulation (simple gel).

The purpose of this study was to develop a new monolithic matrix tablet to completely deliver glipizide in a zero order manner over a sustained period. Two approaches were examined using drug in a formulation that contain polymer like hydroxylpropyl methyl-cellulose K 100 (HPMCK) and Eudragit L100. The granules were prepared by wet granulation method and thereby formulated as F-1, F-2. F-3 and F-4 by using the above bring up polymers with other ingredients. The granules of different formulations were evaluated for angle of repose, loose bulk density and tapped density, compressibility index, total porosity,and drug content. The angle of repose and compressibility index (%) ranged from 25.0±0.8to 28.0±1.1 and 12.92±0.02 to 13.08±0.03, respectively. The results of angle of repose (<30)indicate good flow properties of the granules. This was further supported by lower com-pressibility index values. The granules showed satisfactory flow properties, compressibility and drug content. All of the formulations showed uniform thickness (C.V< 0.5%), uniform weight with little significance difference were observed with varying formulation composition.In the weight variation test, the pharmacopoeial limit for the percentage of deviation for tablets of more than 130 mg to 324 mg is 7.5 % difference. Technological characterizations (thickness, diameter, weight variation test, drug content, hardness, and friability) were conceded with the formulated matrix tablet and in vitrodrug release was measured by meansof dissolution apparatus. Of the various formulation distinguished, out of which, theformulation (F3) were preferred to be full of 30 mg of HPMCK and 35 mg of Eudragit L100was subjected to stability were accomplished studies for three months at 4 °C. The roomtemperature (25 °C) and (45 °C) with relative humidity 75±5% were maintained and itsstability with respect to release pattern. The kinetic release treatment showed that therelease of drug follows zero order kinetic (r2= 0. 9959), Koresmeyer equation gave valueof r2= 0.9853 which was close to one indicating that the drug was released by zero orderkinetic. According to Koresmeyer equation, the formulation F-1, F-2, and F-4 showed the regression values of 0.9823, 0.9785, and 0.9742, respectively. The identical plot for (logcumulative percentage drug release vs time) for Koresmeyer-Peppas equation indicated agood linearity for the commercially available sustained release tablet and formulation F-3 with regression values of 0.9619 and 0.9959, respectively. Scanning electron microscope confirmed both diffusion and erosion mechanism for the optimized batch of matrix tabletF-3. Results suggest that the formulated tablet F-3 of glipizide could perform therapeuti-cally better than the reachable marketed drug leading to improve better efficacy.

The purpose of this work was to develop once daily sustained release (SR) matrix tablets of naproxen, an anti-inflammatory agent. The tablets were prepared by wet granulation method along with hydrophilic matrix materials like Methocel K 15M CR and Methocel K 100M CR. The granules were evaluated for bulk density, angle of repose, compressibility index, total porosity and drug content. The tablets subjected to thickness, diameter, weight variation test, drug content, hardness,friability, and in vitrorelease studies in buffer medium (pH, 7.4). The granules prepared either by Methocel K 15M CR or Methocel K 100M CR did not show satisfactory flow properties and compressibility, and had difficulty in sieving and individual in drug release. On the other hand, tablet matrix prepared along with Methocel K 15M CR and Mehtocel K 100 LVCR polymers of the proposed formulation F-8 showed desired drug release up to 24 h. All the formulations followed first order release kinetics (except F-2 and F-4), exhibited diffusion dominated drug release when data plotted into Korsmeyer Peppas equation. The matrix tablet of naproxen using hydroxypropyl methylcellulose derivatives controls the drug release effectively for 24 h; hence, the formulation can be considered as once daily sustained release tablet of naproxen in order to improve patient compliance.

A new series of thiazolidinedione derivatives were synthesized. The structures of these compounds were established by means of IR, 1H-NMR and elemental analysis. All of the compounds were screened for antidiabetic activity on albino rats.Most of the compounds showed significant antidiabetic activity when compared with the standard drug glibenclamide.

A sensitive and rapid method is described for determination of clopidogrel carboxylic acid (CCA), the inactive metabolite of the antiplatelet agent clopidogrel in human serum. The analytical procedure involves liquid-liquid extraction of the analyte and an internal standard (phenytoin) with ethyl acetate. Amobile phase consisting of 0.05 M phosphate buffer containing triethylamine (0.5 ml/l; pH 5.7)and acetonitrile (56:44; v/v) was used and chromatographic separation was achieved using a C18analytical column at detector wavelength of 220 nm. The calibration curves were linear over a concentration range of 0.05-10 μg/ml of CCAin human serum. The total run time of analysis was 5.5 min. and the lower limits of detection (LOD) and quantification (LOQ) were 0.02 and 0.05 μg/ml, respectively. The method validation was carried out in terms of specificity, sensitivity, linearity,precision, accuracy and stability. The validated method was applied in a randomized cross-over bioequivalence study of two different clopidogrel preparations in 24 healthy volunteers.

Genistein is a soya isoflavone, which is found naturally in legumes, such as soybeans and chickpeas. The intraperitoneal administration of the optimum dose (200mg/kg) of genistein 24 h and 15 minbefore irradiation (8 Gy at a dose rate of 1.02 Gy/min) recovered the deficit in protein content (28.63±1.44%) and the DNA content (21.61±8.19%) if an average of 5 intervals of autopsies 1st, 3rd, 7th, 15th and 30thdays are taken into consideration as compared to those of control group in Swiss albino mice. The decrease of protein amount after irradiation may be due to its lysis by gamma radiation or may be at the synthesis level or it may be due to the depression of enzymes involved in the activation of amino acids and transferring to tRNAor by the inhibition of release of synthesized polypeptides from polysomes.The decrease in DNAcontent after irradiation is due to an inhibition of replication of this compound in nucleus and accumulation of ribonucleotide in the cytoplasm,which is based on the inability, of irradiated cell to reduce ribonucleotide to DNA in the nucleus. The results indicate that genistein against radiation effect may pave way to the formulation of medicine in radiotherapy for normal tissue.

Adverse drug reaction (ADR) is one of the most life threatening problems, and the economic burden of ADR is considerable. The main objective of this study was to assess the attitude of the Kerman health system staff, to evaluate their knowledge of the spontaneous reporting system and to identify the reasons for low reporting rate. In this descriptive study, a Persian translated questioner was used based on standard European pharmacovigilance research group. Among 800 distributed questionnaires, 78% were filled and returned. Returned questioner (82%) indicated to have already suspected an ADR but only 4% reported it to Iranian ADR centre.The 4 major reasons for not reporting were: a) reporting process was unknown (65%),b) Iranian pharmacovigilance centre was unknown for the staff (45%), c) the yellow cards for reporting ADR were not available (30%), and d) ADR were not important (22%). We concluded that our medical staff's knowledge about ADR is little. Appropriate teaching and acceptable effort is needed to strengthen the current system and to prevent other serious ADRs.