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ABSTRACT: A sensitive high performance liquid chromatographic (HPLC) method involving fluorescence detection was developed for the determination of fexofenadine (FEX), known to have low oral bioavailability, in rat plasma. In order to understand the effect of various chromatographic factors on the separation of analytes and to simultaneously optimize the resolution and analysis run time, a response surface method was used. The chromatographic separation was achieved using a Supelco C(18)-DB (250 mm x 4.6mm I.D./5 microm particle size) column with mobile phase comprising of ammonium acetate buffer and acetonitrile (63:37, v/v), delivered isocratically at a flow rate of 1.0 mL min(-1). Diphenhydramine was used as an internal standard (I.S.). The statistical evaluation of the method was examined and the method was found to be precise and accurate with a linearity range of 1-500 ng mL(-1) (r>0.9980). The intra- and inter-day precision studies showed good reproducibility with coefficients of variation (C.V.) less than 12.26%. The advantages of our method are small sample volume (100 microL), short time of analysis (13 min) and a simple sample extraction and clean-up as compared to the previously published methods. The established method provides a reliable bioanalytical methodology to carry out FEX pharmacokinetics in rat plasma.
Talanta 07/2008; 76(2):338-46. · 3.79 Impact Factor
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ABSTRACT: The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.
Archives of Pharmacal Research 03/2007; 30(2):222-34. · 1.59 Impact Factor
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ABSTRACT: A simple, selective, precise and stability-indicating high-performance thin-layer chromatographic method of analysis of imatinib mesylate both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of chloroform:methanol (6:4, v/v). The system was found to give compact spot for imatinib mesylate (R(f) value of 0.53+/-0.02). Densitometric analysis of imatinib mesylate was carried out in the absorbance mode at 276 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2)=0.9966+/-0.0013 with respect to peak area in the concentration range 100-1000 ng per spot. The mean value+/-S.D. of slope and intercept were 164.85+/-0.72 and 1168.3+/-8.26 with respect to peak area. The method was validated for precision, recovery and robustness. The limits of detection and quantitation were 10 and 30 ng per spot, respectively. Imatinib mesylate was subjected to acid and alkali hydrolysis, oxidation and thermal degradation. The drug undergoes degradation under acidic, basic, oxidation and heat conditions. This indicates that the drug is susceptible to acid, base hydrolysis, oxidation and heat. Statistical analysis proves that the method is repeatable, selective and accurate for the estimation of said drug. The proposed developed HPTLC method can be applied for identification and quantitative determination of imatinib mesylate in bulk drug and dosage forms.
Journal of Pharmaceutical and Biomedical Analysis 02/2007; 43(2):722-6. · 2.97 Impact Factor
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U Mandal, P Musmade,
A Ghosh,
Mita Chakraborty,
M Jayakumar,
D Senthil Rajan,
M Chakravarty,
T K Pal,
T K Chattaraj,
Krishnangshu Roy,
S N Banerjee
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ABSTRACT: Gatifloxacin is a broad spectrum fluoroquinolone that offers enhanced Gram-positive activity and anaerobic coverage to other fluoroquinolones. The pharmacokinetic parameters (Cmax, AUCo-t, tmax) of this drug have been evaluated to compare the single dose (400mg) bioavailability of gatifloxacin with the reference formulation. High performance liquid chromatography (HPLC) coupled with U-V detector set at 290 nm has been used to determine plasma concentration of 12 human volunteers as per DCGI (Drug Controller General of India) guidelines. The method has been validated over a linear range of 0.25 to 8 microg/ml from plasma. The minimum quantifiable concentration has been set at 0.25 microg/ml (% CV < 10%). The pharmacokinetic parameters are: Cmax = 4.366 +/- 0.44 microg/ml at tmax = 1.83 +/- 0.44 hour, AUCO0-t = 25.26 +/- 2.91 microg hour/ml, AUCo-inf = 33.68 +/- 4.31 microg hour/ml, Kel = 0.094 +/- 0.024/hour and t1/2 = 8.0 +/- 1.92 hour.
Journal of the Indian Medical Association 10/2004; 102(9):488, 490, 492 passim.
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ABSTRACT: The aim of the present study is to increase the aqueous solubility of celecoxib by recrystallization from distilled water, Tween-80, and polyethylene glycol-400. The prepared crystals were evaluated for various physicochemical evaluations, dissolution rate, and in vivo performance like analgesic activity (by writhing and hot plate method) and pharmacokinetics in mice. The practical yield of the crystals ranged between 83 and 98%, and celecoxib content was more than 99%. Celecoxib showed an almost 5-fold increase in solubility when recrystallized in the presence of Tween-80 (2%). The dissolution rates of celecoxib from the co-crystal forms were considerably higher than that of plain celecoxib. The infrared and differential scanning calorimetry studies indicated the absence of a well-defined interaction between celecoxib and carriers. The differential scanning calorimetry and X-ray diffraction studies indicated the amorphization or partial amorphization of the drug. The scanning electron microscopy showed fluffy, porous, and fine particles in recrystallized celecoxib. The particle size of prepared co-crystals was considerably reduced in comparison with plain celecoxib. The crystals prepared with Tween-80 (2%) showed significantly higher analgesic activity than plain celecoxib. In pharmacokinetic study, the prepared crystals exhibited significantly high and rapid absorption along with improved bioavailability.
PDA journal of pharmaceutical science and technology / PDA 61(5):362-74.
