Mini Review on Forced Degradation Studies on Anti-Epileptic Drugs and Beyond.

In this review on the forced degradation studies on anti-epileptic drugs and the development of validated stability-indicating assay methods for drug substances and products at a condition more severe than accelerated condition (i.e. 40 ± 2°C, 75 ± 5% relative humidity), the drug substance and drug product undergo degradation is known as forced or stress degradation. To know about the impurities developed during the storage of drug products in various environmental conditions. The limit of degradation allowable is 5-20%. More than 20% of degradation is abnormal and must be investigated. Any regulatory guidelines do not mention the pH conditions for acid or base hydrolysis, the temperature for thermal degradation or the concentration of the oxidation agent. Only International Conference on Harmonization (ICH) guidelines Q1B photostability stability and states that light sources must be a combination of UV and visible light. The shortcomings of mentioned techniques with appreciation to regulatory necessities are highlighted. A systematic method for the forced degradation studies on anti-epileptic drugs such as "Topiramate, Vigabatrin, Lacosamide, Tiagabine, Levetiracetam and Zonisamide" is discussed. This review helps researchers to get an idea about stability-indicating methods of development and validation for newer antiepileptic drugs and the characteristics of drug products that degrade under specific degradation conditions.

New stability chiral RP-HPLC method for degradation products determination in midodrine hydrochloride.

Enantiomeric resolution of the drug and complete separation from its degradation products was successfully achieved on a PAK IG-3 (150 × 4.6 mm i.d., 3 µm particle size) column, using UV detector at a wavelength of 290 nm, with mobile phase consisting of acetonitrile, 20 mM ammonium bicarbonate at the ratio of 95:05 (v/v), and a flow rate of 0.7 mL/min. In order to subjected to stress conditions, the drug has been exposed to alkaline, acidic, neutral, oxidative, and photolytic conditions. The products of degradation were well resolved from the main peak and proved the method's stability-indicating method. The method linear ranged between 10-110 µg/mL and 5-100 µg/mL for (+) and (-) midodrine enantiomers and regression analysis showed a correlation coefficient value (r2) of 0.999. The recovery of the method was found to be in the range of 99.1-101.2%. The detection limit for the (+) and (-) enantiomers was found to be 4 µg/mL and 1 µg/mL, respectively. The HPLC method was validated as per ICH guidelines with respect to specificity, precision, linearity, and robustness.

A systematic approach for stability-indicating HPLC method optimization for Nilotinib bulk through design of experiments: Application towards characterization of base degradation products by mass spectrometry.

A novel and reliable stability-indicating high-performance liquid chromatography method was developed using design of experiments. Under forced degradation conditions (hydrolysis, oxidative, photolytic and thermal) Nilotinib produced five major degradation products utilizing sodium hydroxide in base hydrolysis. The degradation products were separated by Hypersil ODS column (150×4.6mm i.d., 5µ) utilizing methanol and 10mM ammonium acetate (pH 3.0, adjusted with acetic acid) as mobile phase in gradient elusion mode at a flow rate of 1.2mL/min column temperature set at 35°C and UV detection at 263nm. Tandem mass spectrometry method was used to characterize the base degradation products by accurate mass measurements. The developed method was found to be linear, accurate, precise and selective for the separation of Nilotinib from its degradation products as per the International Conference on Harmonisation guidelines. The structures of the degradation products have been elucidated, of which three degradation products were reported for the first time.

Physicochemical, pharmacokinetic, and pharmacodynamic characterization of isradipine tablets for controlled release.

Isradipine is a dihydropyridine calcium channel blocker (CCB) commonly used as vasodilator with antihypertensive properties. A remote-controlled release formulation for isradipine would substantially improve the clinical outcomes of the patients requiring chronic long-term treatment. In this work, sustained release (SR) tablets of isradipine, composed of hydroxypropylmethyl cellulose (HPMC), have been produced by wet granulation and their in vitro and in vivo characterization was compared to a conventional tablet dosage form of immediate release (IR) as preliminary assessment. Tablets composed of 15.0% (wt/wt) HPMC exhibited a SR profile over a period of 24 hours. The release of isradipine followed a Fickian diffusion pattern obeying to the first order kinetics and the extent of absorption was even higher in comparison to the developed conventional tablets, which showed immediate drug release. In vivo studies were carried out in rabbits, showing that the extent of isradipine absorption from the developed tablets was higher in comparison to IR tablets due to the modified release profile obtained for the former (p < 0.05). Our results suggest that SR tablets of isradipine are an efficient solid dosage form to overcome the limitations encountered in conventional IR tablets.

Review of pesticide residue analysis in fruits and vegetables. Pre-treatment, extraction and detection techniques.

A wide variety of pesticides have been used in agriculture to increase the yield, quality and extend the storage life of crops. However, the use of pesticide has been increased now a day due to the ever-increasing population and rapid urbanization. The continuous uses of these pesticides have resulted in contamination of the environment, crops and also caused potential risk to human health. For this reason, strict regulations are developed and regulated to monitor these compounds. To date, several techniques have been developed for the extraction and detection of pesticides, from traditional to advanced detection techniques. The present study delineates a comprehensive up to date overview of the available traditional methods (gas chromatography and high-performance liquid chromatography coupled with various detector) to advanced pre-treatment (polystyrene-coated magnetic nanoparticle) and detection (sensor development and nanotechnology) techniques used in the analysis of pesticides residue in various fruits and vegetables. Also, categorization of pesticides and its toxicity have been discussed.

Multivariate response surface methodology assisted modified QuEChERS extraction method for the evaluation of organophosphate pesticides in fruits and vegetables cultivated in Nilgiris, South India.

An effective, simple and sensitive analytical method has been developed employing liquid chromatography coupled with tandem mass spectrometry and validated for estimation of five organophosphate pesticides at trace levels in six fruits and twelve vegetables. Plackett-Burman design and central composite design was used to screen and optimize the significant factors in modified QuEChERS (quick, easy, cheap, effective, rugged and safe) extraction method. The method evaluation was done by matrix-matched calibration with linearity ranging from 5 to 500 µg/L with a correlation coefficient more than 0.990. The detection and quantification limit ranged from 0.1 to 1.0 µg/kg and 0.5 to 5 µg/kg, respectively. The mean recoveries were in the range of 76.89-110.30 % with the relative standard deviation less than 13.26% for all pesticides. Further, the method developed was applied to analyze real samples cultivated in the hill areas of Nilgiris, South India.

Experimental design in pesticide extraction methods: A review.

The sample extraction process is considered as the essential step in the pesticide residue analysis, as it provides the base for the detection of the pesticides in trace level. Various factors need to be optimized during the extraction of pesticides due to the complexity of the matrix which is time-consuming and tedious. Therefore, the use of experimental design in the optimization process proves to be effective with minimum experiments and cost. This paper is aimed to overview the experimental designs that are frequently used for screening (full factorial, fractional factorial, Plackett-Burman Design) and optimizing (central composite design, Box-Behnken design, Taguchi design, Doehlert design, D-optimal design) the most influential factors to provide a sequential understanding of the linear and complex interactions in the pesticide extraction methods. Further, a systematic approach has been discussed about the use of experimental designs in pesticide extraction and also the softwares used for application-oriented readers.

A Sensitive RP-HPLC Method for Simultaneous Estimation of Diethylcarbamazine and Levocetirizine in Tablet Formulation.

A simple, sensitive and reproducible method was developed and validated for the simultaneous estimation of diethylcarbamazine and levocetirizine in its tablet formulation by reverse phase high performance liquid chromatography using Waters1515 HPLC with UV detector at the λ(max) of 224 nm, using Princeton Sphere-100 C(18) (250×4.6 mm. 5 µ) column. The mobile phase used was 20mM potassium dihydrogen orthophosphate buffer (pH: 3.2):acetonitrile (50:50 v/v) with isocratic flow (flow rate 1 ml/min) and the pH was adjusted with orthophosphoric acid. Losartan potassium was used as an internal standard. The compounds diethylcarbamazine, levocetirizine and losartan potassium were eluted at 2.12, 4.27 and 5.96 min, respectively. The peaks were eluted with better resolution. The method was accurate with assay values of 96.32 and 93.04% w/w, precise (%RSD) with intra-day 1.72 and 1.89 and inter-day 1.85 and 1.92, recoveries 102.86 and 101.1% w/w, which are very sensitive with limit of detections (LOD)'s 75, 50 ng/ml and limit of quantification (LOQ)'s 100, 75 ng/ml and linear with R(2) values 0.994 in the range of 5 to 30 µg/ml 0.1 to 1 µg/ml for diethylcarbamazine and levocetirizine, respectively. Hence this method can be applied for quantification of different formulations containing diethylcarbamazine and levocetirizine simultaneously.

A Validated RP-HPLC Method for Simultaneous Estimation of Nebivolol and Hydrochlorothiazide in Tablets.

A simple, selective, rapid, precise and economical reverse phase high pressure liquid chromatographic method has been developed for the simultaneous estimation of nebivolol and hydrochlorthiazide from pharmaceutical formulation. Phenomenex Gemini C(18) (25 cm×4.6 mm i.d., 5 µ) column with a mobile phase consisting of acetonitrile: 50mM ammonium acetate (adjusted to pH 3.5 using orthophosphoric acid) (70:30 v/v) at a flow rate of 1.0 ml/min was used. Detection was carried out at 254 nm. Probenecid was used as an internal standard. The retention times of probenecid, nebivolol and hydrochlorthiazide were 13.05, 3.32 and 4.25 min, respectively. The developed method was validated in terms of accuracy, precision, linearity, limit of detection, limit of quantitation and solution stability. The proposed method can be used for the estimation of these drugs in combined dosage forms.

HPTLC method for the simultaneous determination of amlodipine and benazepril in their formulations.

A new, simple, precise, rapid, and selective high-performance thin-layer chromatographic (HPTLC) method is developed for the simultaneous analysis of amlodipine and benazepril in pharmaceutical formulations. The method uses zolpidem as an internal standard (IS). The stationary phase used is silica gel 60 F254 prewashed with methanol. The mobile phase consists of an ethyl acetate-methanol-ammonia solution (8.5:2.0:1.0, v/v/v). Detection and quantitation are performed densitometrically at lambda = 254 nm. The Rf values of amlodipine, benazepril, and zolpidem (IS) are 0.58, 0.50, and 0.78, respectively. The limits of detection of amlodipine and benazepril are 0.02 and 0.2 microg; linearity ranges are 0.1-0.8 and 0.2-2.0 microg; and the percentage recoveries are 99.79% and 100.25%, respectively.

Análisis de la simvastatina en preparaciones farmacéuticas mediante cromatografía de capa fina de alto rendimiento / Analysis of simvastatin in pharmaceutical preparations by high performance thin layer chromatography

Se ha desarrollado un nuevo método de cromatografía de capa fina de alto rendimiento (HPTLC) sencillo, preciso, rápido y selectivo para el análisis de la simvastatina en preparaciones farmacéuticas. En este método se utiliza la fexofenadina como estándar interno. La fase estacionaria era gel de sílice 60 F254 prelavado con metanol; como fase móvil se utilizó solución de acetato de etilo, metanol y amoniaco al 25 por ciento (7:1,5:0,5 v/v). La detección y la cuantificación se realizaron densitométricamente a Landa= 220 nm. El rango lineal del análisis fue 0,08 - 0,8 µg y la recuperación porcentual 100,7 por ciento (AU)