Current Issue : October - December Volume : 2011 Issue Number : 4 Articles : 14 Articles
Nonclinical pharmacokinetic (PK) and toxicokinetic (TK) toxicology safety studies are performed using goodlaboratory practice (GLP) regulations to ensure the availability of safe medicines. International GLP regulationsuniformly require that dose concentration, homogeneity/uniformity and stability be known prior to administration.However, the United States Food and Drug Administration (US FDA) and the Organisation for Economic Co-operation and Development (OECD) both confirmed that GLPs do not apply to validation of analytical methodsused to determine the concentration of GLP test article in drug dosage forms. It is our assertion that the outcomeof nonclinical toxicology safety studies is inherently dependent upon accurate and precise dose formulations.In this paper, we attempt to provide supporting evidence as to why formulation method validation and sampleanalysis for supporting nonclinical toxicology studies should be consistently conducted under the framework ofGLP principles across the globe. GLP studies are planned, performed, monitored, recorded, reported and archivedaccording to a protocol, study plan or standard operating procedure (SOP) which is authorized prior to performingthe experiments. All applicable experimental parameters and associated acceptance criteria are pre-defined. TheFDA asked for responses to the Advance Notice of Proposed Rulemaking for 21 CFR Part 58 GLPs for NonclinicalLaboratory Studies [Docket No. FDAââ?¬â??2010ââ?¬â??Nââ?¬â??0548] on December 21, 2010. Several comments were receivedstating that guidance regarding the validation of formulation analysis methods and subsequent use for supportingGLP toxicology study sample analysis is warranted at this time and should be conducted consistently. Adherence toGLP principles for method validation and sample analysis would inherently improve the quality of nonclinical safetystudies. Furthermore, the recently published White Paper titled, ââ?¬Å?Nonclinical dose formulation analysis methodvalidation and sample analysisââ?¬Â should be the keystone of this effort....
The documentation system is one of the mandatory elements reviewed during inspections of any regulatory agency. Generally, 20 to 30 percent of the deviations detected in a pharmaceutical inspection, are directly related to the documentation of quality system in each of the components or systems inspected. Given that no regulation on GMP will tell us in detail how the documentation system should be, we aimed to show in this work an approach used to implement some of the quality tools for establishment and maintenance of GMP and inherent Documentation in order to comply with the normative, national and international regulations typical of a productive process monoclonal antibody (MAb) which is secreted by the hybridoma 48/1/5/4, specific for the ââ?¬Å?aââ?¬Â determinant of the Hepatitis B surface antigen (HBsAg). This MAb is routinely used as reagents for the purification of vaccines.\r\n \r\nThe work was separated into three basic stages: Diagnosis and Assessment of Specific and General Documentation of the System; Maintenance and improvements to the document system and New regulatory perspectives. The effective functioning of a documentation system in which the main objective has been to guarantee stable and solid production processes for the preparation of biopharmaceutical products, allowing the release and commercialization of a considerable number of utility batches for human health....
To develop simple, rapid, accurate, precise and reproducible reversed phase high performance liquid chromatographic method has been developed for the estimation of Coumarin in bulk and in tablets. Development of method for Coumarin determination of by RP-HPLC was undertaken using new mobile phase of Methanol: water (70:30 v/v). The eluent was monitored at 300 nm. The optimized conditions developed showed a linear response from 2 to 20 ug/mL with correlation coefficient of 0.9998. The retention time of drug was found to be 3.2 minutes. The limit of detection (LOD) and limit of quantification (LOQ) were 0.025 and 0.037ug/mL. Recovery data were good. Placebo study for specificity and interference of common excipients showed that the method was specific and free from interfering substances. Therefore, the fully validated method developed was sensitive enough to carry out analysis of Coumarin in tablet formulations with regard to its run time, simplicity of sample preparation and accuracy....
A simple, reproducible and efficient reverse phase high performance liquid chromatography (RP-HPLC) method has been developed for estimation of Amlodipine Besylate and Enalapril Maleate in its tablet dosage forms by using C-8(4.6* 250 mm, i.d. 4.6 micrometer) column. Acetonitrile: Water, pH 3.8 with glacial acetic acid (60:40) as mobile phase. The detection wavelength is 223 the method was demonstrated to be precise, accurate, specific and robust....
Novel combination of Fexofenadine hydrochloride (FEXO) and Montelukast Sodium (MTKT) is available as tablet dosage form in the ratio of 12:1 and no spectrophotometric method has been reported yet. The present research work aims to develop a simple, sensitive, accurate and reproducible method for the simultaneous estimation of both drugs by the first derivative spectrophotometric method, using methanol: water (20:80) as a solvent. The Method was performed at 212.60(zero crossing point of montelukast sodium) and 340.60(zero crossing point of fexofenadine hydrochloride) for Fexofenadine hydrochloride and Montelukast sodium respectively. The regression analysis data for the calibration plot showed good linear relationship in the concentration range of 4‐24 μg/ml (R2 = 0.9999) for Fexofenadine hydrochloride and 4‐24 μg/ml (R2 = 0.998) for Montelukast sodium. The average percentage recovery of Fexofenadine hydrochloride and Montelukast sodium combination was found to be 103.00% and 103.47% respectively. The LODs for Fexofenadine hydrochloride and Montelukast sodium were 1.895 μg/ml and 2.7055 μg/ml and LOQs were found to be 5.743 μg/ml and 8.198 μg/ml respectively. Statistical analysis proves that the method is reproducible and selective for the simultaneous determination of Fexofenadine hydrochloride and Montelukast sodium. The Results were found to be within acceptance criteria according to ICH Q2 R1 guidelines....
A simple, sensitive, precise & stability indicating RP-HPLC method was developed & validated for the determination of Tramadol hydrochloride in tablet dosage form. The chromatographic conditions comprised of column XTerra® C 18 column (250 mm, id 4.6 mm, 5 µm),Water Ireland using mobile phase phosphate buffer : acetonitrile (75:25 v/v) at a flow rate of 1.5 ml/min at an ambient temperature. The retention time of tramadol was 6.49 min. Tramadol hydrochloride was subjected to acid & alkali hydrolysis, oxidation, photochemical determination & thermal degradation. The degraded product was well separated from the drug. The linear regration analysis data for the calibration plots showed regration value 0.9999 in the concentration range 200.60-601.80.The value of slope & intercept were 20.87 & -6.87 respectively. The method was validated for precision, recovery, ruggedness & robustness. The drug undergoes degradation under acidic, basic, photochemical & thermal....
A method for determining prochloraz in ten herbal medicines is described. Pesticide standards were fortified into herbal medicines at 3 levels (0.005, 0.01 and 0.05mg/kg). Prochloraz reacts with pyridine hydrochloride and generates a hydrolysate, the 2,4,6-trichlorophenol which responded intensively in GC-ECD. The results showed average recoveries were between 76.6% and 105.1%. The method evidenced good accuracy and precision for monitoring prochloraz in ten herbal medicine samples. The limit of quantification (LOQ) was 0.005mg/kg. It is linear from 0.005 mg/L to 2.000mg/L. The regression equation is y=3816.1x-7.7835, R=0.9997....
The importance of betahistine dihydrochloride as an anti-vertigo medicine and of etilefrine hydrochloride in the management of hypotension necessitates the development of a simple, sensitive and inexpensive technique for their analysis. This study reports the development of an accurate, feasible kinetic technique for their determination. It is based on the reaction of the cited drugs with 4-chloro-7-nitrobenzofurazan (NBDââ?¬â??Cl) in presence of 0.05 M disodium hydrogen phosphate. The absorbance was measured at 496, and 503 nm for betahistine dihydrochloride and etilefrine hydrochloride respectively, at a fixed time of 30 minutes on thermostated water bath at 90Ã?°C. The absorbance concentration plots were rectilinear over the range 0.25ââ?¬â??7 and 3ââ?¬â??13 Ã?µg/ml for betahistine dihydrochloride and etilefrine hydrochloride, respectively. The method has been applied successfully to commercial tablet dosage form and can be further applied for their determination on a large scale in quality control laboratories, or in small laboratories. The obtained results statistically agreed with those obtained by official titrimetric methods. The determination of the studied drugs by the fixed concentration and rate constant methods is feasible with the calibration equations obtained, but the fixed time method proves to be more applicable....
A simple, rapid and sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay for the determination of simvastatin in human plasma using lovastatin as internal standard (IS) was established. After being extracted by methyl tert-butyl ether, solutes were separated on a C18 column with a mobile phase consisting of methanol-water-5M ammonium acetate (90:10:0.1, v/v/v). The quantification of target compounds was carried out by using multiple reaction monitoring (MRM) mode: m/z 419.2 ? 199.1 and 405.1 ? 285.1 for simvastatin and IS, respectively. The method had a run time of 3.3 min and a linear calibration curve in the range of 0.1-20 ng/ml. The lower limit of quantification (LOQ) was about 0.1 ng/ml. The mean extraction recovery of simvastatin was over 92.48%. Intra- and inter-day variability values were less than 10.5% and 9.30%, respectively. This method offered good precision and accuracy and was successfully applied for a bioequivalence studies of 20 mg of simvastatin orally disintegrating tablets in 20 Chinese healthy volunteers....
The primary aim of this research was to assess the rich source of photochemical present in C. Gigantea. Calotropis gigantea, an important medicinal plant is one of the most widely cultivated species of the family Asclepiadaceae. It is highly valued from time immemorial because of its vast medicinal properties. Every part of Calotropis is said to have beneficial properties that can serve humanity so the whole plant can be extensively studied for further research aspects. Calotropis gigantea better known as laticiferous shrubs is a plant widely distributed in Indian. The plant is known to be medicinally important. Among the solvent extract methanol gave more effective than ethanol, Chloroform, benzene and petroleum ether for C. Gigantea. In the present study, the present research work was therefore undertaken to investigate the presence of major classes of phytoconstituents in the seeds methanoic extract of C. gigantea by using sophisticated analytical tool like HPTLC....
Two simple, precise and cost effective spectrophotometric methods have been developed for the estimation of Valsartan in bulk and its pharmaceutical formulations. Valsartan shows λmax at 250 nm in zero order derivative spectrum (Method A) and 265 nm in first order derivative spectrum (Method B). The drug follows the Beer-Lambert’s law in the concentration range of 10–55 µg/ml in both the methods. The methods were validated by following the analytical performance parameters as suggested by the International Conference on Harmonization which included accuracy, precision, interday and intraday assay, robustness, and ruggedness. All validation parameters were within the acceptable range. The developed methods were successfully applied to estimate the amount of Valsartan in bulk and pharmaceutical dosage forms. This method can be used for the routine estimation of Valsartan in industries and other analytical laboratories and also in dissolution studies....
A stability indicating, simple, economic, rapid, precise and sensitive reverse phase high performance liquid chromatography method was developed and validated for determination of Omeprazole and Diclofenac sodium in capsule dosage form. The quantitative determination of Omeprazole and Diclofenac sodium was performed on an BDS Hypersil C18, 250 mm X 4.6 mm, 5 µm, stainless steel analytical column from Thermoscientific with mobile phase consist of Ammonium acetate buffer (0.05M) :Acetonitrile (55:45 %v/v), pumped at a constant flow rate of 1 mL min-1. The detection is carried out using variable wavelength UV-Vis detector set at 289.0 nm. The method shows good peak shape, minimal tailing, with retention time 4.79 min and 6.62 min for Omeprazole and Diclofenac sodium. The both drugs was subjected to acidic, alkaline, oxidation, photo-degradation to apply stress conditions. The developed method was able to separate degradation product generated under forced degradation studies. The developed method was validated as per ICH guidelines for the parameters such as specificity, linearity, accuracy, precision, limit of detection, limit of Quantitation and found to be satisfactorily. The response was linear in the drug concentration range of 4-20 µg mL-1 (r2 = 0.998) and 20-100 µg mL-1 (r2 = 0.998) for Omeprazole and Diclofenac sodium. The proved to be suitable for stability testing, homogeneity testing and quality control of this compound in capsule dosage form....
Churnas are important group of formulations used by Ayurvedic and Siddha physicians to treat various types of diseases. Amlakyadi churna is an important ayurvedic formulation, is official in Ayurvedic formulary of India is combination of four reputed herbs, comprised of the fruits Embelica officinalis, Piper longum, Terminalia chebula and roots of Plumbago zylenica and Sendha namak. The formulation is dispensed for the treatment of digestive impairment, fever and dyspepsia. Through the Ayurvedic powder formulation enjoys great reputation, its standardization and quality control parameters are not well defined. . The efforts have been initiated to develop certain methods and parameters for standardization and quality control. In house preparations (thee batches) of churna were prepared as per Ayurvedic Formulary of India. The preparations were standardized according to guidelines of World Health Organization (WHO). Evaluation of quality control parameters for Amlakyadi churna includes determination of extractive values, ash values, foaming index, and swelling index, determination of pH value, various physical parameters and preliminary phytochemical screening. In the present study comparative study of laboratory formulation with established marketed formulation were performed. The results of studies performed on formulation found to be precise, reproducible and can be considered for routine quality control of the formulation....
A new, simple, precise and accurate method for the estimation of Albendazole in bulk and pharmaceutical dosage forms has been developed. 0.1N HCl was chosen as the solvent system. The λmax was found to be 230nm. The responses were linear in the range of 10-70µg/ml. The regression equation of the calibration graph and correlation coefficient were found to be y = 0.032x + 0.014 and 0.999 respectively. The proposed method was statistically validated in order to demonstrate the accuracy, precision, interday and intraday assay, robustness, and ruggedness. The %RSD values for both intraday and interday precision were less than 1%. The recovery of the drug from the sample was ranged between 97.792% and 100.49%. Different commercial formulation (tablets) containing 400mg of Albendazole (BANDY, BENDEX, NOWORM, and ANTHEL) were analyzed by the proposed method and the results were found to be satisfactorily within the claimed limits. This method can be used for the routine estimation of Albendazole in industries and other analytical laboratories and also in dissolution studies....
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