Showing papers by "Kadi Sarva Vishwavidyalaya published in 2013"

Innovation of novel 'Tab in Tab' system for release modulation of milnacipran HCl: optimization, formulation and in vitro investigations.

Abstract: The study was aimed toward development of modified release oral drug delivery system for highly water soluble drug, Milnacipran HCl (MH). Novel Tablet in Tablet system (TITs) comprising immediate and extended release dose of MH in different parts was fabricated. The outer shell was composed of admixture of MH, lactose and novel herbal disintegrant obtained from seeds of Lepidium sativum. In the inner core, MH was matrixed with blend of hydrophilic (Benecel®) and hydrophobic (Compritol®) polymers. 32 full factorial design and an artificial neuron network (ANN) were employed for correlating effect of independent variables on dependent variables. The TITs were characterized for pharmacopoeial specifications, in vitro drug release, SEM, drug release kinetics and FTIR study. The release pattern of MH from batch A10 containing 25.17% w/w Benecel® and 8.21% w/w of Compritol® exhibited drug release pattern close proximal to the ideal theoretical profile (t50% = 5.92 h, t75% = 11.9 h, t90% = 18.11 h). The phenomen...

Development of carbamazepine transnasal microemulsion for treatment of epilepsy

Abstract: Carbamazepine is widely preferred therapy for the treatment of epilepsy. However, oral therapy results in slower brain uptake and systemic side effects. Intranasal route can achieve faster brain uptake, but poor aqueous solubility of carbamazepine is the main obstacle for administration by nasal route. The purpose of this study was to prepare and evaluate intranasal oil in water microemulsion of carbamazepine to improve its solubility and enhance the brain uptake. Intranasal microemulsion of carbamazepine was prepared by water titration method using oleic acid as oil, Tween 80 as surfactant and Transcutol® as cosurfactant. Microemulsions were evaluated for various physical parameters including globule size, viscosity, pH and conductivity. Toxicity study of microemulsion was carried out by employing sheep nasal mucosa. The microemulsion was also evaluated by maximal electric shock, and the brain uptake study was done using HPLC method. The microemulsion was stable and transparent with average globule size of 21.03 nm and did not show any toxic symptoms. It showed reduction in the hind limb extension phase and faster recovery from seizures in comparison to oral microemulsion and nasal solution. Higher brain/plasma ratio was obtained with nasal microemulsion in comparison to ratio obtained after intraperitoneal injection of carbamazepine solution.

Stable-isotope dilution LC-MS/MS assay for determination of iloperidone and its two major metabolites, P 88 and P 95, in human plasma: application to a bioequivalence study.

Abstract: Background: Iloperidone is a novel antipsychotic drug with high affinity for serotonin and D2 dopamine receptors. A sensitive and rapid isotope dilution LC–MS/MS method has been developed for the simultaneous determination of iloperidone and its two major metabolites in human plasma. Results: The analytes and their deuterated analogs as internal standards were quantitatively extracted from 100-µl human plasma by SPE. The method was validated over the concentration range of 0.01–6 ng/ml for all the analytes. Baseline separation of analytes was possible within 3 min on ACE 5 C8 column. The accuracy and precision (%CV) of the method varied from 96.2 to 105%, and 1.17 to 4.75%, respectively. The extraction recovery was >84%, while the internal standard-normalized matrix factors ranged from 0.97–1.03 for all three analytes. Conclusion: The developed method was successfully applied to support a bioequivalence study in healthy volunteers.

Rapid and sensitive simultaneous estimation of metformin hydrochloride and pioglitazone hydrochloride in tablet formulation by hptlc method

Abstract: A rapid, simple, and sensitive HPTLC method for simultaneous estimation of two antidiabetic drugs, metformin hydrochloride and pioglitazone hydrochloride, in pharmaceutical tablet was developed and validated. Separation was achieved on aluminum sheets of silica gel 60 F254 using butanol:1, 4-dioxane:glacial acetic acid (5:3:2, v/v/v) as the mobile phase. This system gave a good resolution for metformin hydrochloride (R f value of 0.36 ± 0.01) and pioglitazone hydrochloride (R f value of 0.73 ± 0.01). Detection and quantification was carried out at 226 nm. Calibration plot was constructed in the range of 2000 to 20000 ng/band for metformin hydrochloride and 60 to 600 ng/band for pioglitazone hydrochloride. The linear regression data for the calibration plot showed a good relationship with r = 0.9960 and 0.9968 for metformin hydrochloride and pioglitazone hydrochloride, respectively. Assays for metformin hydrochloride and pioglitazone hydrochloride were 99.6% (RSD 0.618%) and 99.7% (RSD 0.511%), respectivel...

Quantitative determination of milnacipran HCl in rabbit plasma by HPLC and its application to pharmacokinetics study.

Abstract: A simple, sensitive, and specific reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for the quantification of Milnacipran HCl in rabbit plasma. Milnacipran HCl and internal standard (IS, Venlafaxine HCl) were extracted by protein precipitation method with chloroform. The separation was performed on a HiQ sil C18 column (250 mm × 4.6 mm i.d., 5 µm). The wavelength was set at 220 nm. The mobile phase was a mixture of potassium dihydrogen phosphate buffer (0.0125 M) and acetonitrile (72:28%, v/v) with 0.20% triethylamine at a flow rate of 1.0 mL/min. The pH of the solution was adjusted to 3.65 with 0.1 M orthophosphoric acid. The calibration curve was linear over the concentration range 0.1-25 µg/mL. The intra-day and inter-day precision was ranged from 3.9 to 7.3% and 5.2 to 10.8%, respectively. Finally, this proposed method was successfully applied to rabbit pharmacokinetics study and yielded the most comprehensive data on systemic exposure of Milnacipran HCl to date.

Ex vivo conversion of prodrug prothionamide to its metabolite prothionamide sulfoxide with different extraction techniques and their estimation in human plasma by LC-MS/MS.

Abstract: Background: The present work reports an ex vivo conversion study of prothionamide to its active metabolite prothionamide sulfoxide in human plasma during sample preparation by three conventional extraction techniques. Results: The chromatography was done on a Hypersil™ Gold C18 (50 × 2.1 mm, 3.0 µm) column using 0.1% acetic acid and acetonitrile (20:80, v/v) as the mobile phase. Quantitation of the analytes was done by MS/MS in the positive ionization mode. The method was validated over a wide concentration range of 30 to 6000 ng/ml for prothionamide and 50 to 10,000 ng/ml for prothionamide sulfoxide. The recovery for both the analytes was greater than 89%. Stability was extensively validated under different storage conditions. Conclusion: The extraction protocol was optimized using acetonitrile as protein precipitant for their simultaneous determination in human plasma by LC–MS/MS. The method was applied to a bioequivalence study of 250 mg prothionamide tablet formulation in 14 healthy Indian subjects.

Rapid and sensitive simultaneous estimation of metformin hydrochloride and pioglitazone hydrochloride in tablet formulation by HPTLC method.

Abstract: A rapid, simple, and sensitive HPTLC method for simultaneous estimation of two antidiabetic drugs, metformin hydrochloride and pioglitazone hydrochloride, in pharmaceutical tablet was developed and validated. Separation was achieved on aluminum sheets of silica gel 60 F254 using butanol:1, 4-dioxane:glacial acetic acid (5:3:2, v/v/v) as the mobile phase. This system gave a good resolution for metformin hydrochloride (Rf value of 0.36 ± 0.01) and pioglitazone hydrochloride (Rf value of 0.73 ± 0.01). Detection and quantification was carried out at 226 nm. Calibration plot was constructed in the range of 2000 to 20000 ng/band for metformin hydrochloride and 60 to 600 ng/band for pioglitazone hydrochloride. The linear regression data for the calibration plot showed a good relationship with r = 0.9960 and 0.9968 for metformin hydrochloride and pioglitazone hydrochloride, respectively. Assays for metformin hydrochloride and pioglitazone hydrochloride were 99.6% (RSD 0.618%) and 99.7% (RSD 0.511%), respectively, for the brand analyzed. The method was validated for precision and recovery. The limits of detection and quantification were 629.89 and 1908.76 ng/band for metformin hydrochloride and 8.51 and 25.77 ng/band for pioglitazone hydrochloride, respectively.