PREPERATION AND IN VITRO EVALUATION OF SOLID DISPERSIONS OF NIMODIPINE USING PEG 4000 AND PVP K3

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. The aim of the present study was to improve the solubility and dissolution rate of a poorly water-soluble drug, nimodipine, by a solid dispersion technique. Solid dispersions were prepared by using polyethylene glycol 4000 (PEG- 4000) and polyvinylpyrrolidone K30 (PVPK30) in different drug-to-carrier ratios. The solid dispersions were prepared by melting method. Morphology of solid dispersions was characterised by scanning electron microscope. The pure drug, physical mixtures and solid dispersions were characterized by in vitro dissolution study. Dissolution characteristics were determined by using pH 4.5 acetate buffer containing 0.3% SDS. The very slow dissolution rate was observed for pure nimodipine and the dispersion of the drug in the polymers considerably enhanced the dissolution rate. This can be attributed to improved wettability and dispersibility, as well as decrease of the crystalline and increase of the amorphous fraction of the drug. Solid dispersions prepared with PEG-4000 and PVPK30 showed the highest improvement in wettability and dissolution rate of nimodipine. Even physical mixtures of nimodipine prepared with both polymers also showed better dissolution profile than that of pure nimodipine. In conclusion, dissolution of nimodipine can be enhanced by the use of hydrophilic carriers PEG-4000 and PVPK30

CONTROLLED RELEASE LAYERED MATRIX TABLETS OF ITOPRIDE HYDROCHLORIDE: IN VITRO AND IN VIVO EVALUATION

Objectives: The tablets were prepared by wet granulation method using polyethylene oxide, which was used to prepare both the matrix core andbarrier layers. In vitro dissolution studies were carried out on the developed formulations. Based on the dissolution data, the best formulation waschosen, and evaluated for its controlled release in healthy human volunteers.Results: When the dissolution data was analyzed, IMP3L2 has shown the highest R value (0.9866) with at least 80% of the drug released in 12 hrsamong all the formulations. Hence, the formulation IMP3L2 was chosen as an ideal formulation and selected for in vivo studies in human volunteers.Eight healthy volunteers participated in the study, and a two-way crossover design was followed. The serum concentration of itopride hydrochloridewas estimated by reverse-phase high-performance liquid chromatography. The pharmacokinetic parameters were calculated from the serumconcentration of itopride hydrochloride versus time data. The delayed Tmax2, decreased Ka, unaltered bioavailability, and prolonged t, indicated a slowand prolonged release of itopride hydrochloride from polyethylene oxide layered matrix tablets in comparison with the plain matrix tablet.Conclusion: Based on the results of in vitro and in vivo studies, it was concluded that polyethylene oxide based layered matrix tablets provided oralcontrolled release of itopride hydrochloride.Objective: In this study, layered matrix tablets of itopride hydrochloride were formulated using polyethylene oxide as release retardant to achievea zero order drug release. The objective of the study was to develop a formulation which will release at least 80% of the drug in 12 hrs and show acorrelation coefficient (R2) value of at least 0.95.Keywords: Layered matrix tablets, Itopride hydrochloride, Polyethylene oxide, High-performance liquid chromatography, Serum

DETERMINATION AND VALIDATION OF A HPLC METHOD WITH UV DETECTIONOF ITOPRIDE HYDROCHLORIDE IN HUMAN SERUM

Objective: Determination and validation of a simple, sensitive and rapid reversed phase high-performance liquid chromatography method for the determination of itopride hydrochloride in human serum using nimesulide as an internal standard.Methods: A liquid-liquid extraction method was employed to extract itopride hydrochloride from serum matrix with diethyl ether. Chromatographic separation was obtained within 10 min using a reverse phase C18 column (250 mm×4.6 mm, 5 µm) with an isocratic elution. The mobile phase consisting of a mixture acetonitrile and 0.05M phosphate buffer with a flow rate of 1.0 ml/min was used and the eluents were monitored at 258 nm.Results: Calibration curves were linear (r2= 0.9987) in the range of 10ng/ml to 1000 ng/ml. The limit of quantitation was 14ng/ml. The mean recovery of itopride hydrochloride and the nimesulide from the biological matrix was more than 66.04 and 64.57%, respectively. The inter-day accuracy of the drug containing serum samples was more than 97.81% with a precision of 2.31–3.68%. The intra-day accuracy was 96.91% or more with a precision of 5.17–9.50%.Conclusion: The developed method was validated and successfully applied to a bioequivalence study in healthy human volunteers.Â

DESIGN, OPTIMIZATION AND IN VITRO CHARACTERIZATION OF SELF NANO EMULSIFYING DRUG DELIVERY SYSTEM OF OLMESARTAN MEDOXOMIL

Objective: The objective of the present study was to design, optimise and characterise self nano emulsifying drug delivery systems (SNEDDS) for a poorly water soluble drug, olmesartan medoxomil (OLM) by Formulation by Design (FbD) approach with an aim to improve its solubility and dissolution.Methods: The SNEDDS were systematically optimised using three factor Box-Behnken design. Concentration of formulation variables, namely, the oil phaseX1 (Capryol 90), the surfactant X2 (Cremophor EL), and the co-surfactant X3 (Transcutol P), was optimized for its impact on mean globule size (Y1), percentage drug release in 20 min (Y2) and turbidity (Y3) of the formulation. Ternary phase diagrams were constructed to select the areas of nanoemulsion and the amounts of oil, surfactant and cosurfactants as critical formulation variables. The prepared SNEDDS were characterised for globule size, dissolution studies, turbidity, and transmission electron microscopy (TEM).Results: Following optimisation, the values of formulation variables were found to be 142.276 mg (Capryol P), 399.999 mg (Cremophor EL) and 598.871 mg (Transcutol P) which produced a globule size of 12.64 nm, percentage drug release of 93.34% and a turbidity of 0.02 FNU. TEM studies demonstrated spherical droplet morphology.Conclusion: Thus, the present studies reveal that the SNEDDS is a promising drug delivery system approach for the enhancement of solubility and dissolution rate of OLM

OPTIMIZATION OF COCONUT OIL BASED SELF MICRO EMULSIFYING DRUG DELIVERY SYSTEMS OF OLMESARTAN MEDOXOMIL BY SIMPLEX CENTROID DESIGN

Objective: To develop and optimize self-micro emulsifying drug delivery systems of Olmesartan Medoxomil using formulation by design approach for improvement of solubility and dissolution rate. Methods: A simplex centroid design was employed as statistical tools to optimize the formulation variables, X1 (Coconut oil), X2 (Kolliphor RH) and X3 (PEG 400). The high and low levels of these factors were selected according the micro-emulsion region obtained from the pseudo-ternary phase diagram. The response variables studied were mean globule size (Y1) and average absorbance (Y2). Results: The optimized formulation consisted of 21.54% of coconut oil, 36.04% of Kolliphor RH and 42.42% of PEG 400 which could provide a globule size of 125.94 nm and an average absorbance of 0.85. Dissolution studies revealed a marked increase in dissolution of the optimized formulation when compared with the pure drug. Conclusion: Thus, it was concluded that self-micro emulsifying drug delivery systems (SMEDDS) provided a promising formulation approach for the solubility and dissolution enhancement of the poorly soluble drug, Olmesartan Medoxomil

Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BACKGROUND: Terminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats. METHODS: The blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test. RESULTS: The chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated. CONCLUSION: The present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects

Anti-Hyperglycemic and Renal Protective Activities of Andrographis paniculata Roots Chloroform Extract

The chloroform extract of Andrographis paniculata roots was tested for its antihyperglycemic activity in alloxan induced diabetic rats using chronic and acute studies. The blood glucose lowering activity was determined after oral administration at doses of 50, 100 and 150 mg/kg body weight in acute study. Where as in case of chronic study blood glucose, protein, albumin and creatinine levels were estimated after 4 weeks of treatment at the dose of 300 mg/kg. Significant reductions in blood glucose levels were observed in both acute and chronic studies. The extract significanly inhibited the induction of albuminuria, proteinemia and uremia. The present study clearly indicated a significant antidiabetic activity with the chloroform extract of A. paniculata roots and supports the traditional usage of the plant by Ayurvedic physicians for the control of diabetes. Also the extract is useful in preventing the incidence of long-term complication, diabetic nephropathy

In vitro Lipase Inhibitory Effect of Thirty Two Selected Plants in Malaysia

Background: Obesity is a metabolic disorder that results from imbalance between energy intake and expenditure. Among many approaches in the treatment of obesity, lipase inhibitory potential in natural products is the most sought after, due to its effects in decreasing fat absorption without altering any central mechanisms. Objective: The objective of this study was to evaluate anti-obesity lipase inhibitory activities from thirty two medicinal and food plants in Malaysia. Materials and Methods: In the present study, methanolic extracts of thirty two selected plants which are known to have ethnomedicinal values or food plants, were investigated for lipase inhibition properties using porcine pancreatic lipase assay (PPL: triacylglycerol lipase, EC 3.1.1.3) in vitro. Results: Among the thirty two local plant species examined, four plants exhibited inhibition activities of more than 15 %. Eleusine indica showed the highest pancreatic lipase inhibitory activity of 31.36 %, followed by ripe female mace of Myristica fragrans (20.23 %), Melastoma candidum (19.67 %), Phyla nodiflora (18.26 %), ripe male mace of Myristica fragrans (17.99 %), respectively. There is no significant difference between activity produced by Eleusine indica methanolic extract and the standard drug Orlistat. Conclusion: Crude methanolic extracts of Eleusine indica, Myristica fragrans, Melastoma candidum and Phyla nodiflora were found to be possible candidates for further studies to isolate potential pancreatic lipase inhibitor among the thirty two different plants screened. Keywords: Eleusine indica, in vitro lipase inhibitory activity, Melastoma candidum, Myristica fragrans, Phyla nodiflor

ANTIDIABETIC ACTIVITY OF ORTHOSIPHON STAMINEUS BENTH ROOTS IN STREPTOZOTOCIN INDUCED TYPE 2 DIABETIC RATS

Objective: The objective of the study is to evaluate ethanolic extract of Roots of Orhtosiphon stamineus for antidiabetic activity in streptozotocin (STZ) induced type 2 diabetic rats. Methods: In short-term study, STZ induced type 2 diabetic rats were administered with single administration of various doses of methanolic extract (200mg/kg, 400mg/kg and 800mg/kg) and changes in blood glucose levels is evaluated. In long-term study, STZ induced type-2 diabetic rats were treated for four weeks with various doses of methanolic extract (200 mg/kg, 400 mg/kg and 800 mg/kg). Blood glucose levels reduction was monitored at weekly intervals. At the end of the experiment, changes in insulin levels, Glucose-6-phosphatase, Glucose-6-phosphate dehydrogenase and glycogen were evaluated. For both the studies glibenclamide (600 μg/kg) is used as standard drug for comparison. Results: Significant reduction in blood glucose levels (p<0.01) was observed with all the doses after 2 h of single dose administration and the effect was dose dependent. Significant reduction in blood glucose levels and dose dependent effect was observed in long-term study. Significant changes in insulin levels were not observed after four weeks of treatment with extract. O. stamineus has shown significant reduction in glucose-6-phosphatase and significant increase in glucose-6-phosphate dehydrogenase and glycogen levels.  Conclusion: Results showed that O. stamineus extract possessed significant antidiabetic activity in type 2 diabetic rats which is due to attenuation of glucose-6-phosphate dehydrogenase, glycogen storage and reduced glucose-6-phosphatase which rationalizes its promising use for treatment of diabetes in future. Keywords: O. stamineus roots, type-2 diabetes, glucose levels, glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, glycogen