Arumugam Karthik

Enhanced oral absorption of saquinavir with Methyl-Beta-Cyclodextrin-Preparation and in vitro and in vivo evaluation.

Saquinavir (SQV) is a weak base compound, whose solubility is strongly influenced by pH variations. Thus, in the present work, we thought it worthy of interest to investigate in-depth the combined effect of pH control and cyclodextrin (CyD) complexation on SQV solubilization. Phase-solubility studies were performed by adding excess drug to buffered (pH from 1.1 to 7.4) aqueous solutions containing increasing concentrations of Methyl-Beta-CyD (M-β-CyD) in order to evaluate the role of the unionized species of SQV in improving solubility by CyD complexation and to be able to select the most suitable conditions for optimizing drug solubilization. Our study reveals that the integrated approach of pH adjustment and CyD complexation can be successfully used for improving the CyD solubilizing power towards an ionizable drug such as SQV, thus allowing a smaller quantity of CyD to solubilize a given amount of drug, offering clear economic and technologic advantages as well. When biopharmaceutics of the optimized cyclodextrin-based formulation of SQV was studied in Wistar rats after intravenous and oral administrations, we found that inclusion of SQV into M-β-CyD could dramatically improve its oral bioavailability and decrease the variation of its oral pharmacokinetics. Compared to the control, the presence of M-β-CyD significantly increased the area under the plasma concentration-time curve (439.7±161.35 to 2312.03±159.53, p<0.01) and the peak plasma concentration (117.24±35.77 to 1347.88±276.76, p<0.01) of orally administered SQV. The modulating effect of M-β-CyD on the bidirectional transport of SQV was also investigated using a modified Ussing chamber system. The results demonstrated that the enhancing effect of M-β-CyD on the oral bioavailability of SQV is due not only to its solubilizing effect on SQV but also, at least in part, to the inhibitory effect of M-β-CyD on the P-glycoprotein (P-gp) mediated efflux of SQV in the gastrointestinal tract. The present results suggest that M-β-CyD is particularly useful in designing oral preparations of SQV with an enhanced bioavailability and a reduced variability in absorption.

Simultaneous estimation of paracetamol and domperidone in tablets by reverse phase HPLC method

A simple, fast, precise and accurate liquid chromatographic method was developed for the simultaneous estimation of paracetamol and domperidone in combined dosage forms. This combination is used for antiemetic and pain associated with gastrointestinal disorders. Drugs are chromatographed on a reverse phase Kromasil C18 column using a mobile phase, 20 mM phosphate buffer (pH 7.0±0.1) and acetonitrile in the ratio of 60:40%v/v. Diclofenac potassium was used as an internal standard. The retention time of paracetamol, domperidone, and diclofenac potassium was 2.94, 8.30, 5.67 min, respectively. The validation of the proposed method was also carried out. The method was found to be linear (r>0.99), precise (%RSD: 0.49% for paracetamol and 0.89% for domperidone), accurate (overall average recovery yields: paracetamol 99.1% and domperidone 98.36%) and selective. Due to its simplicity and accuracy the proposed method can be used for routine quality control analysis of these drugs in combined dosage form.

Determination of telmisartan by HPTLC — A stability indicating assay

Hypertension is the most prevalent disease worldwide and requires constant monitoring. The trend in cardiovascular drug research has been to develop new compounds acting on very specific targets, for example cell-surface receptors. Angiotensin II receptors are long-acting and well tolerated. Telmisartan (Figure 1) is a new benzimidazole derivative antagonist of the subtype angiotensin II (AT-II) receptor intended for treatment of essential arterial hypertension. It is highly safe with excellent efficacy and few side-effects [1, 2].

Stability-Indicating HPTLC Determination of Rivastigmine in the Bulk Drug and in Pharmaceutical Dosage Forms

A. simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic method for analysis of rivastigmine in the bulk drug and in a capsule formulation has been established and validated. Chromatographic separation was achieved on aluminum-backed silica gel 60F254 HPTLC plates with chloroform-methanol 4:6 (v/v) as mobile phase. Densitometric analysis of rivastigmine was performed in absorbance mode at 210 nm. The method gave a compact spot for rivastigmine (RF 0.53 ± 0.02) and was shown to enable excellent separation of a degradation product of rivastigmine (RF 0.32 ± 0.02). The method was validated for accuracy, precision, linearity, recovery, limits of detection and quantitation, and robustness. Good linearity was observed in the concentration range 200-1600 ng per spot; the correlation coefficient was 0.9916 ± 0.008. The limits of detection and quantitation were 30 and 100 ng per spot, respectively. Rivastigmine was subjected to alkaline hydrolysis and high humidity and found to degrade under these conditions. Statistical analysis proved the method was reproducible, specific, and accurate. The method is stability indicating; because it is economical it can be used for routine analysis of the bulk drug and pharmaceutical formulations.

High-performance thin-layer chromatographic analysis of bicalutamide in bulk drug and liposomes

A sensitive, accurate, precise, and specific high-performance thinlayer chromatographic (HPTLC) method for analysis of bicalutamide in the bulk drug and in a liposomal formulation containing cholesterol and lecithin and other surfactants has been established and validated in accordance with ICH guidelines. HPTLC on aluminum foil-backed silica gel 60F-254 plates with toluene-ethyl acetate 4.5:5.5 (v/v) as mobile phase gave compact bands for bicalutamide (RF 0.45). Leflunomide (RF 0.85) was used as internal standard. Densitometric analysis of bicalutamide was performed in absorbance mode at 273 nm. The method was validated for accuracy, precision, linearity, robustness, and limits of detection and quantitation. The method is specific, selective, and free from matrix interferences at the RF of bicalutamide and the internal standard. Regression data for the calibration plots were indicative of a good linear relationship (correlation coefficient 0.9994 ± 0.002) between response and amount of bicalutamide in the concentration range 200–1600 ng per band. The limits of detection and quantitation were 50 and 200 ng per band, respectively.

High-Performance Thin-Layer Chromatographic Determination of Etoricoxib in the Bulk Drug and in Pharmaceutical Dosage Form

A sensitive, accurate, precise, and stability-indicating high-performance thin-layer chromatographic method has been established and validated for analysis of etoricoxib in both bulk drug and formulations. Chromatography is performed on aluminum-backed silica gel 60F254 plates with toluene-1,4-dioxane-methanol 8.5:1.0:0.5 (v/v) as mobile phase. This system furnished compact bands for etoricoxib (RF 0.24). Rofecoxib (RF 0.38) was used as internal standard. Densitometric analysis of etoricoxib was performed in absorbance mode at 235 nm. Linear regression data for the calibration plots showed there was a good linear relationship between response and amount of etoricoxib in the range 100-1500 ng per spot; the correlation coefficient was 0.9922 ± 0.001. The mean values of the slope and intercept of the plot were 280.14 ± 0.26 and 320.01 ± 0.22, respectively. The method was validated for precision, accuracy, robustness, and recovery. The limits of detection and quantitation were 30 and 100 ng per spot, respectively. The drug undergoes degradation when subjected to neutral, acidic, or basic hydrolysis, oxidation, or dry heat treatment, but the degradation products were well separated from the drug (different RF values). Because the method could effectively separate the drug from its degradation products it can be regarded as stability-indicating.

Fluorimetric Determination of Rivastigmine in Rat Plasma by a Reverse Phase — High Performance Liquid Chromatographic Method

A sensitive and selective high performance liquid chromatographic (HPLC) method was developed and validated for the rapid quantification of rivastigmine (CAS 123441-03-2) in micro quantity in rat plasma samples. The chromatographic separation was achieved with a reverse phase monomeric column C18 (4.6 x 250 mm, 5 microm) and the mobile phase consisted of acetonitrile and 20 mmol/L phosphate buffer pH 3.0 (25:75) with a flow rate of 1 mL/min. The effluents were measured by fluorimetric detection with excitation and emission wavelengths at 220 nm and 293 nm, respectively. The calibration curve was linear (r2 > 0.99) ranging from 25-3000 ng/mL and the lower limit of quantification was 25 ng/mL. The method was validated with excellent sensitivity, selectivity, accuracy, precision, recovery and stability. The method has been successfully applied in a pharmacokinetic study of rivastigmine in rats.

Novel liquid chromatographic method for simultaneous estimation of pioglitazone and glimepiride in rat plasma by solid phase extraction: application to preclinical pharmacokinetic studies.

The need for a reliable bioanalytical method is of primary importance during preclinical studies. The aim of the present study was simultaneous determination of pioglitazone (CAS 111025-46-8) (PIO) and glimepiride (CAS 93479-97-1) (GLM) in plasma of rats. A high-performance liquid chromatographic method has been developed and validated using C18 column and UV detector. A mobile phase composed of acetonitrile and ammonium acetate buffer pH 4.5 in the ratio of 55:45%. The plasma samples clean-up was carried out using solid phase cartridges. The method was in the linear range of 50-8000 ng/mL for PIO and 50-2000 ng/mL for GLM. The coefficient of regression was found to be > or = 0.99. Precision and accuracy were within the acceptable limits, as indicated by relative standard deviation varying from 1.5 to 6.1% for PIO and 3.1 to 7.0% for GLM whereas the accuracy ranged from 97.0 to 106.4% for PIO and 96.5 to 106.4% for GLM. The mean extraction recovery was found to be 90.2 +/- 4.5, 76.8 +/- 2.8 and 85.2 +/- 5.2% for PIO, GLM and internal standard, respectively. Moreover, PIO and GLM were stable in plasma, up to 30 days of storage at -70 degrees C and after being subjected to bench top, auto-sampler, and three freeze-thaw cycles. The developed method was applied for preclinical pharmacokinetic studies.

Dissolution development of valdecoxib tablets

Valdecoxib is a nonsteroidal antiinflammatory drug, and it is listed in class 2 of biopharmaceutic classification of drugs. Valdecoxib is a poorly water-soluble and highly permeable drug. In the present study a new dissolution medium was developed, as there is no official dissolution medium available in the literature. The composition of the dissolution medium was selected on the basis of solubility data at 37°. Solubility data revealed that addition of surfactant may be suitable as dissolution medium. The concentration of 0.6% w/v sodium lauryl sulphate in water could be a suitable dissolution medium. The discriminating power of the selected dissolution medium (0.6% sodium lauryl sulphate in water) relative to the other dissolution mediums was evaluated. The selected dissolution medium was used for the evaluation of valdecoxib tablets.

Stability-Indicating HPTLC Determination of Capsaicin in the Bulk Drug

A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for analysis of capsaicin in the bulk drug has been developed and validated. The method employs aluminum TLC plates precoated with silica gel 60F254 as stationary phase. The mobile phase was toluene-ethyl acetate 6:4 (v/v). A compact spot was obtained for capsaicin (RF 0.38 ± 0.02). Densitometric analysis of capsaicin was performed in absorbance mode at 280 nm. Regression analysis of calibration data revealed a good linear relationship (r2 > 0.9936) for peak-area data in the concentration range 100-1000 ng per band. The method was validated for accuracy, precision, linearity, limit of detection, limit of quantitation, and robustness. The limits of detection and quantitation were 20 and 60 ng per band, respectively. Capsaicin was subjected to acidic and alkaline hydrolysis, oxidation, and thermal degradation. The drug undergoes degradation under acidic, basic, and oxidizing conditions and at elevated temperatures. Statistical analysis proved the method enables precise, selective, and accurate analysis of capsaicin. The method can be used for identification and quantitative analysis of capsaicin in the bulk drug.