S. M. Ashraful Islam

Preparation and evaluation of SEDDS of simvastatin by in vivo, in vitro and ex vivo technique.

Abstract The objective of this work was to formulate a Self Emulsifying Drug Delivery System (SEDDS) of simvastatin, a poorly soluble drug and to evaluate by in vivo, in vitro and ex vivo techniques. Oils and surfactants were screened out depending upon their solubilizing capacity. Among all of the solvents, Capryol 90 showed good solubilizing capacity. It dissolved 105 mg/ml of simvastatin. Tween-80 also showed good solubilizing capacity which was 117 mg/ml. The two excipients were used to prepare simvastatin SEDDS. Formulations were initially checked for the color, clarity and sedimentation. The SEDDS formulations were transparent and clear. Formulation F2 containing 7:3 (m/m) mixture of Capryol 90/Tween-80 produced smallest micro-emulsion with particles size of 0.074 µm and drug release was higher than other formulation (102% within 20 min). Ex vivo study of the SEDDS formulation was evaluated using guinea pig intestinal sac. Drug diffused from F2 formulation was significantly higher than pure drug (p < 0.001). In vivo study of SEDDS was performed in albino mice using plasma cholesterol level as a pharmacodynamic marker parameter. The test formulation (F2) appeared remarkable reduction in plasma cholesterol level, after oral administration which showed that SEDDS may be an effective technique for the oral administration of simvastatin.

Formulation and Evaluation of Bi-layered Sustained Release Matrix Tablets of Tramadol Hydrochloride

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique incorporating an immediate release layer and a sustained release layer. An immediate release layer was successfully designed to release the bolus dose instantaneously. Water soluble Xanthan gum, water insoluble Kollidon SR and Eudragit L 100 were used as carriers in the sustained release layer of the matrix tablet. All the tablets were evaluated for thickness, diameter, weight variation, hardness and friability. The in vitro drug release was studied for eight hour, first two hours dissolution in acidic medium followed by six hour dissolution in buffer medium. Matrix tablet showed a sustained release rate with a controlled fashion as a function of the quantity of polymer used. The in vitro drug release data were fitted with several mathematical models and mean dissolution time along with fractional dissolution time values (T25%, T50% and T80%) were calculated. Xanthan gum was found to be the most effective rate retarding agent compared to Kollidon SR and Eudragit L 100, when used at same ratio in the formulations.

Evaluation of In Vitro Equivalence for Tablets Containing the Poorly WaterSoluble Compound Atorvastatin

This paper describes the evaluation of the in vitro equivalence of tablets containing a poorly water-soluble compound, atorvastatin, marketed in Bangladesh under biowaiver conditions. Drug release was compared with that of a reference product. The in vitro equivalence test was carried out in three different media (pH 1.2, pH 4.5, and pH 6.8). Test results were subjected to statistical analysis to compare the dissolution profiles. Model-independent approaches of difference factor (f1), similarity factor (f2), and dissolution efficiency (%DE) were employed. Dissolution profiles of test and reference (innovator) atorvastatin are equivalent at pH 6.8 without statistical treatment. The test products are equivalent at pH 4.5 (f1 50) and not equivalent at pH 1.2 (f1 > 15 and f2 < 50). Other general quality parameters of these tablets (e.g., weight variation, crushing strength, friability, and disintegration time) were also determined according to established protocols, and test results were within limit. INTRODUCTION Some drugs that have a good clinical therapeutic effect often show low systemic availability because of poor water solubility. Up to 40 percent of new chemical entities discovered by the pharmaceutical industry today are poorly soluble or lipophilic compounds. The solubility issues complicate the delivery of these new drugs and many existing drugs (1). Poorly water-soluble drugs show unpredictable absorption and high intrasubject and intersubject variability (2–4). Therefore, constant surveillance of marketed, poorly water-soluble drugs by the government, manufacturers, and independent research groups is essential to ensure availability of quality medicines. Atorvastatin, a synthetic lipid-lowering agent, is an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis (5). The calcium salt of atorvastatin is currently used for the treatment of hypercholesterolemia (6). The intestinal permeability of atorvastatin is high at the physiologically relevant intestinal pH (7, 8). However, it has been reported that the absolute bioavailability of atorvastatin is only 12% after a 40-mg oral dose (9). The low systemic availability is attributed to low dissolution, presystemic clearance in gastrointestinal mucosa, and hepatic first-pass metabolism (10). Atorvastatin calcium is a crystalline powder and is insoluble in aqueous solution at pH 4 and below. It is very slightly soluble in water. The solubility in aqueous solution at pH 2.1 is about 0.0204 mg /mL, while the solubility in pH 6.0 aqueous solution is about 1.23mg/mL (11). The dose/ solubility (D/S) ratio for atorvastatin is greater than 250 mL for the 10-mg dose at pH 1.2, although the drug dissolves in 250 mL of buffer solution at pH 6.8. Therefore, atorvastatin is a low solubility drug according to WHO Guidance (12). Atorvastatin is not listed in the WHO Model list and is not classified according to BCS by WHO (13). Because of its solubility (low) and permeability (high), atorvastatin is assigned to BCS Class 2 according to WHO guidance. We selected atorvastatin tablets to evaluate the quality of locally available, lipid-lowering drugs with special emphasis on the study of disintegration and dissolution properties of the test samples due to their immense importance in predicting drug bioavailability as well as product quality. We used USP buffer solutions of pH 1.2 (hydrochloric acid solution), pH 4.5 (acetate buffer solution), and pH 6.8 (phosphate buffer solution). Six units were tested for dissolution. Other general quality parameters of these tablets like weight variation, crushing strength, friability, disintegration time were also determined according to established protocols. The test results were subjected to statistical analysis to compare the dissolution profile. Model independent approaches of difference factor (f1), similarity factor (f2), and dissolution efficiency (%DE) were employed. MATERIALS AND METHODS Chemicals Standard atorvastatin calcium was a kind gift from Incepta Pharmaceuticals Ltd., Bangladesh. Three brands *Corresponding author. e-mail: ashraf@uap-bd.edu dx.doi.org/10.14227/DT190412P30

Pattern and treatment of Gout in Bangladesh: a hospital based survey at Dhaka city, Bangladesh

Gout is a common metabolic disorder which occurs due to excessive deposition of uric acid in different bone joints. Increasing life expectancy, life style change, changes in diet are causing an increased incidence of the disease nowadays. The present study was aimed to understand the pattern and treatment of gout in Bangladesh. 150 patients at four tertiary care hospitals in Dhaka city were surveyed. The findings of the present study suggests that both male and female are suffering from the disease and age seems to be related to the disease as 62% of gout patients were found over 50 years of age. Body weight may be a contributing factor of the disease. Most of the gout patients under the survey were suffering from high blood pressure (65.33%). Primary gout was found more prevalent in this investigation (70.66%) and viral hepatitis was found to be the most common cause of the disease (50%). The patients presented common sign and symptoms of gout.