A new, simple and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of rosuvastatin (ROS) and metformin (MET) in human plasma was developed. The assay procedure involved simple protein precipitation with acetonitrile. Following precipitation, fraction of supernatant was decanted and evaporated under gentle stream of nitrogen at 40°C. The residue was reconstituted in mobile phase and injected. The chromatographic separation was achieved with Thermo Hypurity C18 column (50 mm × 4.6 mm, 5 μ) using a mobile phase composition containing 0.1% v/v formic acid in water and acetonitrile (30:70, v/v) at a flow rate of 0.4 mL/min. The total run time was 3.5 min. The method showed good linearity in the range 0.5–200 ng/mL for ROS and 2–2000 ng/mL for MET with correlation coefficient (r) >0.9994 for both the analytes. The intra and inter-day precision values for ROS and MET met the acceptance criteria as per regulatory guidelines. The battery of stability studies viz., bench-top, freeze-thaw and long term stability were performed. The developed method was applied to a pharmacokinetic study.
Background:The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 22 factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation.Materials and Methods:Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 22 factorial designs.Results:The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP.Conclusion:Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology.
Background: The influence of losartan on the hypoglycemic effect of glimepiride was studied in normal and diabetic rats. Method: Losartan and glimepiride were studied at a dose of 4.5 and 0.09 mg/kg and in normal and diabetic rats, respectively. The blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 10, 12, and 16 hours and analyzed for glucose levels using a glucometer. Results: Glimepiride exhibited a maximum reduction of blood glucose levels at the 4th hour in normal and diabetic rats. The maximum hypoglycemic effect was observed at the 6th hour in normal rats treated with losartan. In normal rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in either the single-or multiple-dose interaction study. In the case of diabetic rats, losartan did not have any significant effect on the hypoglycemic activity of glimepiride in the single-dose interaction study, but a significant change was observed in the multiple-dose study of diabetic rats. Hence, the interaction was found to be pharmacodynamic.
Conclusions:The study indicates that chronic losartan pretreatment elevates the hypoglycemic effect of glimepiride by a possible rise in insulin sensitivity and improving insulin homeostasis or may be due to the inhibition of CYP2C9. The study also suggests that caution may be recommended concerning combined use of losartan and an oral hypoglycemic agent, glimepiride.
Objective:Diabetes mellitus is a syndrome of multiple etiologies. Both type 1 and type 2 diabetes lead to multiple abnormalities of lipid and lipoprotein metabolism. The aim of this investigation was to study the influence of fenofibrate on the blood glucose lowering effect of glibenclamide.Materials and Methods:Glibenclamide (0.45, 0.23 mg/kg) and fenofibrate (18.1, 9.38 mg/kg) was treated to normal, diabetic rats, and normal rabbits. Blood samples were collected at various time intervals and were analyzed for blood glucose levels using a glucometer.Results:Co-administration of fenofibrate with glibenclamide significantly elevated the blood glucose reduction exhibited by glibenclamide.Conclusion:The results obtained from single and multiple dose treatments clearly demonstrated the existence of drug-drug interaction at the dose tested in animal models. Hence, this investigation would serve as a preclinical evidence for the effect of fenofibrate on the therapeutic efficacy of glibenclamide.
In vitro release studies were performed for three commercial, modified-release brands of the anti-diabetic drug gliclazide at 30-mg strength. Dissolution media such as 0.1 N HCl (pH 1.2), acetate buffer (pH 4.5), distilled water (pH 7.0), and phosphate buffer (pH 7.4) were evaluated to develop a dissolution method for better evaluation of gliclazide formulations, as there was no official method for gliclazide modified-release tablets. Drug release followed zero-order kinetics in all dissolution media except acetate buffer, where it followed first-order kinetics. The statistically treated data show a significant difference in release rates among the brands. The similarity factor and difference factor values also show the adjustment of differences in release profiles. The drug release studies carried out in 0.1 N HCl show that this medium is the most suitable for providing sink conditions and discriminating conditions.
Verapamil‐releasing transdermal delivery systems were designed and developed using different ratios of hydroxypropylmethylcellulose (HPMC) K4M, K15M, K100M. Formulations were selected on the basis of their drug‐release content and release pattern. These were evaluated for in‐vitro dissolution characteristics using a Cygnus' sandwich patch holder.
The release followed Higuchi kinetics as its coefficient of correlation (r = 0.993–0.997; P < 0.001) predominates over first‐order and zero‐order release kinetics. In‐vivo evaluation was carried out on healthy human volunteers (23.12 ± 1.08 y; 63.83 ± 6.54 kg) following the balanced incomplete block design. Dissolution rate constant (K) and data generated from plasma and urine (Cmax, tmax, AUCs, t1/2, K, t1/2a, Ka) were evaluated statistically by two‐way analysis of variance. Statistically excellent correlation was found between percentage of drug absorbed and Cmax, AUC0‐24 and AUC0‐∝. The time at which maximum lowering of blood pressure was found coincided with the plasma tmax. A highly significant difference (P < 0.001) was observed when Cmax and AUC0‐∝ generated from plasma and urine were compared but when K, t1/2, Ka, t1/2a were compared, a non significant (P > 0.1) difference was observed.
Urinary excretion data is suggested as a simpler alternative to blood level data in studying the kinetics of absorption and deriving the absorption parameter.
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