INTERNATIONAL JOURNAL OF PHARMACEUTICAL QUALITY ASSURANCE
INTERNATIONAL JOURNAL OF PHARMACEUTICAL QUALITY ASSURANCE is a quarterly international journal publishing the finest peer-reviewed research in the field of Pharamceutical Quality Assurance and Pharamceutical Analysis on the basis of its originality, importance, disciplinary interest, timeliness, accessibility, elegance and surprising conclusions. IJPQA also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.
Ground Water Quality of Piro and Jagdishpur Blocks of Bhojpur District: A Middle Gangatic Plain
This communication presents an analysis of physico-chemical characteristics of groundwater quality of Piro and Jagdishpur blocks of Bhojpur District of Bihar. Total 40 numbers of groundwater samples were collected from different locations of these blocks and analysed for the parameters pH, electrical conductivity (EC), total dissolved solid(TDS), total hardness(TH), calcium(Ca²⁺), magnesium(Mg2+),fluoride(F¯), iron(Fe), sulphate(SO42-)and arsenic (As). Water samples were collected from shallow hand pumps, deep hand pumps and public water supply.
Validation of Stability Indicating HPLC Method in the Application of Comparative Pharmacokinetic Studies of Atorvastatin in Different Pharmaceutical Formulations (bulk drug, tablet, and nanoemulsion).
A simple, highly sensitive, isocratic stability indicating reversed phase-high performance liquid chromatography (RP-HPLC) method with UV detection at 247 nm was developed and validated for analysis of Atorvastatin (AT). Diclofenac was used as an internal standard (IS). Retention times of the AT and diclofenac (IS) were found to be 4.2 and 8.2 min, respectively. A mobile phase consisting of 0.05 M sodium phosphate buffer and methanol (30:70 v/v) pH 4.1 at flow rate 1ml/min was employed in this study. The calibration curves were linear with regression coefficient (r²) of 0.9997 ± 0.0014. The limits of detection (LOD) and the limits of quantitation (LOQ) were found out to be 5.0 and 15 ng/ml, respectively. The method was statistically validated in accordance with International Conference on Harmonization (ICH) guidelines. The proposed method is sensitive, specific and was successfully applied for the estimation of atorvastatin in pharmaceutical formulations (bulk drug, tablet, nanoemulsion) and in rat serum pharmacokinetic studies.
Microbiological Quality Assesment of Some Commercial Herbal Drugs
In present study five drug samples viz Zingiber officinalis, Boerhaavia diffusa, Glycerrhiza glabara, Terminalia arjuna, Terminalia chebula were analysed for microbial load(Total bacterial count & total yeast and mould count) and for specific pathogenic bacteria (E.coli, Salmonella spp, Staphylococcus aureus, Pseudomonas aeruginosa) as per WHO norms(Anonymous 1998). Total bacterial load is higher in four samples of herbal drugs (Zingiber officinalis, Boerhaavia diffusa, Glycerrhiza glabara, Terminalia chebula). The total Yeast and mould count in all five samples is beyond the prescribed limits of WHO while Specific pathogenic bacteria are absent in all five sample of herbal drugs.
Spectrophotometric Estimation of Fluvoxamine Maleate in Tablets Using Hydrotropic Agent
Several techniques are used to increase the aqueous solubilities of poorly water soluble drugs. Hydrotropic solubilization technique is one of them. In the present investigation hydrotropic solution of Urea (10M) has been used as a solubilizing agent to solubilize poorly water soluble drug. Fluvoxamine maleate shows maximum absorbance at 271 nm. Beer's law was obeyed in the concentration range of 5-25 µg/ml. Results of analysis were validated statistically and by recovery studies. The proposed method is now simple, new, environmentally friendly, accurate and cost-effictive and successfully employed in routine analysis of fluvoxamine maleate tablets. Hydrotropic agent urea did not interfere in spectrophotometric determination.
Simultaneous Spectrophotometric Estimation of Curcuminoids and Gallic Acid in Bulk Drug and Ayurvedic Polyherbal Tablet Dosage Form
In the present study, an attempt has been made to develop an analytical method for the simultaneous estimation of curcuminoids and gallic acid in commercially marketed ayurvedic polyherbal formulation Nisha Amalaki vatti by spectrophotometric method. Simultaneous equations (Vierodt's method) were performed by UV/Visible spectrophotometric. Curcuminoids has absorbance maxima at about 427nm and Gallic acid maxima at about 227nm in methanol. The linearity was obtained in the concentration range of 10-50 mcg/mL for both curcuminoids and gallic acid. The results were of the analysis were validated statistically and the recovery studies were carried out as per ICH guidelines.
Spectrophotometric Estimation of Torsemide in Tablet Dosage Form Using Chemical Derivatization Technique
A simple and cost effective spectrophotometric method is described for the determination of Torsemidein pure form and in pharmaceutical formulations. The method is based on the formation derivative when the drug reacts with picric acid solution. The colored derivative solution has an absorption maximum at 350 nm; also obeys Beer's law in the concentration range 5-25µg/mL. The absorbance was found to increase linearly with increasing concentration of torsemide, which is corroborated by the calculated correlation coefficient value of 0.997. The slope and intercept of the equation of the regression line are 0.035 and 0.002 respectively. The optimum experimental parameters for the reaction have been studied. The validity of the described procedure was assessed. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The proposed method was successfully applied to the determination of Torsemide in pharmaceutical formulations.
Determination of Thorium (IV) by Derivative Spectrophotometric Technique.
A simple and sensitive spectrophotometric method has been developed for the determination of Thorium (IV) using newly synthesized reagent 3,5-Dimethoxy-4-hydroxybenzaldehyde isonicotinoyl hydrazone (DMHBIH). Thorium (IV) forms an Yellow coloured water soluble complex with the reagent in acidic medium pH 3.0. The molar absorptivity and Sandell's sensitivity of coloured species are 4.84 x 104 L.mol¯¹ cm¯¹ and 0.0083 µg/cm² respectively. Beer's law is obeyed in the range 0.580-5.80 µg/ml of Thorium(IV) at max at 390 nm. Thorium (IV) forms a 1:1 complex and stability constant of the complex is 4.176 x 10º the developed derivative spectrophotometric method has been satisfactorily applied for the determination of Thorium (IV) in monazite sand.
3,5-dimethoxy-4-hydroxybenzaldehyde isonicotinoylhydrazone(DMHBIH)
Physico-chemical Standardization of Butea Monosperma (Lam.) Kuntze (Palasha): An Ayurvedic Drug
The present communication attempts to investigate pharmacognostical and physicochemical analysis and chromatographic profiles of Butea monosperma (Lam.) Kuntze (fabaceae). Flowers are used as drug in many ailments like eye disease, chronic fever, enlargement of spleen, leucorrhoea, epilepsy, leprosy and gout etc. Identification of plants with botanical verifications is essential as adulteration due to misidentification of plant species or parts are common. Standardization of medicinal plant product is the prime need of the current time. The significant popularity of HPTLC in the analytical testing of pharmaceutical, bulk drugs and herbal lends its fame to the attributes. Therefore, HPTLC studies of alcoholic extract of Butea monosperma flowers were also carried out to lay down the fingerprint profile of drug. The study revealed specific identities for Butea monosperma (Lam.) Kuntze, which may play a key role in identification of plant and can be useful in standardization of the herbal drugs.
Simultaneous Estimation of Olmesartan medoxomil and Hydrochlorothiazide by RP-HPLC Method in Combined Tablet Dosage Forms and its Invitro Dissolution Assessment.
A simple, sensitive, rapid and reproducible reversed- phase HPLC method has been developed and validated for estimation of Olmesartan medoxomil and Hydrochlorothiazide simultaneously and also the comparative study of invitro data in tablet formulation. The assay involved an isocratic elution of these two component on Inertsil-phenyl column (25cm X 4.6mm, 5µm) using a mobile phase composition of Buffer: Acetonitirile (480:520) and pH adjusted to 3.0 with dilute orthophosphoric acid. The flow rate was 1.0 mL/min and the analytes monitored at 257nm.Calibration curves were linear with coefficient correlation between 0.99 to 1.0 over a concentration range of 24 to 74 µg/mL of Olmesartan medoxomil and 15 to 47 µg/mL for Hydrochlorothiazide respectively. The invitro release of various test units was compared for their similarity using the f2 test which limits were found with in the acceptance criteria. All the validation parameters were with in the acceptance range according to ICH norms. The described method was successfully employed for quality control assay of both the component simultaneously and dissolution data helpful in generating the further information regarding invivo absorption rate in tablet dosage form.
Development and Validation of HPTLC Method of Fluoxetine Hydrochloride in Bulk and Pharmaceutical Formulation
A simple, accurate, low cost and specific HPTLC method for estimation of Fluoxetine hydrochloride in capsule has been developed. It was performed on Silica gel G60 F254 aluminium foil using Acetone : Methanol in the ratio of 5:4 as mobile phase. The mobile phase containing chamber was saturated for 10 minutes at room temperature. The Rf value of Fluoxetine was found to be 0.12. The plate was scanned and quantified at 226 nm. The calibration curve response was observed between 300-2100 ng. The linear regression data showed good linear relationship of r² = 0.999. The percent recovery was found to be 99.94 ±1.188. The developed method was validated for its accuracy and precision with suitable parameters.
Quality Assessment of Different Variants of Yogaraj Guggulu
Yogaraj-guggulu is a widely used Ayurvedic formulation.Standardisation of the Ayurvedic medicine, Yogaraja guggulu has been achieved by following modern scientific quality control procedures. It has been shown to have significant anti-inflammatory activity in formaldehyde-induced arthritis and in croton oil granuloma. For the standardization of this drug physico-chemical parameters were carried out such as moisture content, ash values, extractability in water and alcohol were carried out. Thin Layer Chromatography studies were also carried out to ascertain the quality of this drug.
Spectrophotometric determination of Metclopramide Hcl using Solochrome black-T
A simple and sensitive visible spectrophotometric method have been developed for the quantitative determination of Metclopromide HCl in its different dosage form (tablet, oral solution and injection). The method is based on the ion pair extraction with chloroform at pH 2.0 using Solochrome black -T as the ion pairing reagent. The spectrophotometric measurement was carried out at the absorption maximum at 505 nm. Beer's law was obeyed in the concentration range of 5- 50 µg/ml with the reagent. The results obtained with the proposed method are in good agreement with the labeled amounts when marketed pharmaceutical preparations are assayed. The recovery was in the range of 98.5-101.5%. Results obtained are statistically validated and found to be reproducible.
Overview of Cleaning Validation in Pharmaceutical Industry
Manufacturing of Pharmaceutical drug products and drug substances shall demonstrate a control to reproduce consistently the desired quality of product, wherein the control of cross-contamination plays an important roll. Residual materials from the previous batch of the same product or from different product may be carried to the next batch of the product, which in-turn may alter the impurity profile of the subjected product. An effective cleaning shall be in place to provide documented evidence that the cleaning methods employed within a facility consistently controls potential carryover of product (including intermediates and impurities), cleaning agents and extraneous material into subsequent product to a level which is below predetermined levels.
Stability Indicating RP-HPLC Method for the Estimation of Trifluoperazine Hydrochloride as API and Estimation in Tablet Dosage Forms
A new stability indicating method was developed for the estimation of trifluoperazine HCl in API, this method was also successfully utilized for the estimation of drug in tablet dosage forms. All the methods were utilized for the degradation of drug i.e. 0.1 N HCI, 0.1 N NaOH, 3 % H2O2, thermal and photodegradation. Drug peak was found to be seperated from all the degradants with resolution of more then two. This method was also used for the estimation of Trifluoperazine HCl in tablet dosage forms. The method was found to be simple, precise, specific and accurate. Developed HPLC method is able to separate all degradants produce form any stress condition from drug peak by resolution of more than 2. The order of stability trifluoperazine HCl was found to be H2O2<UV<alkali<acid<heat. The newly developed method can be used for routine analysis for the estimation of Trifluoperazine HCl in bulk and tablet dosage form in pharmaceutical industry.
Simultaneous Spectrophotometric Estimation Of Dexrabeprazole And Domperidone In Capsule Dosage Form
Three UV spectrophotometric methods for the simultaneous determination of dexrabeprazole (DEXRAB), and domperidone (DOM), in capsules were developed in the present work. Method I is simultaneous equation method, wavelength selected are 258.5 nm (λmax for dexrabeprazole) and 286.5 nm (λmax for domperidone). Method II involves multicomponent mode of analysis, wavelength selected are 258.5 nm (λmax for dexrabeprazole) and 286.5 nm (λmax for domperidone). Method III is area under curve method, wavelength range selected are 263.5-253.5 nm for dexrabeprazole and 291.5-281.5 nm for domperidone respectively. All the methods were found linear between 5-35 µg/ml for dexrabeprazole and 10-70 µg/ml for domperidone. The accuracy and precision of the methods were determined and validated stastically which showed no significant difference between the results obtained by the three methods. The proposed methods are highly sensitive, precise and accurate and therefore can be used for its intended purpose.
Estimation Of Embelin And Strychnine in Krimimudgara Rasa by HPTLC Method
Rasa is important group of formulation used by Ayurvedic Physicians to treat various types of diseases. Krimimudgara Rasa, as per Ayurvedic literatures is used as an anthelmintic drug. It expels the worms present in cough and faeces of human and gives relief from symptoms like indigestion, vomiting, fever, sneezing and pain in stomach. Many manufactures are adding adulterants in Ayurvedic formulations, which render them less effective and lack of phyto/biomarker(s) responsible for their therapeutic efficacy. No method has been developed to check quantity of phytomarker (s) so far. In the present study an attempt has been made to develop a HPTLC method of quantitative estimation of marker compounds, embelin and strychnine in laboratory prepared formulation (LF) and a marketed formulation (MF) of Krimimudgara Rasa. The laboratory formulation (LF) was found to contain 0.254 % of embelin and 0.080 % of strychnine while the market formulation (MF) shows 0.135% of embelin and 0.046% of strychnine. The method develop was found to be accurate, precise, reproducible & simple for quantitative estimation of phytomarkers i.e. embelin and strychnine and can be recommended for routine analysis of formulation containing such drugs.
ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY (UPLC) : A CHROMATOGRAPHY TECHNIQUE
UPLC can be regarded as a new direction for liquid chromatography. UPLC refers to Ultra Performance Liquid Chromatography.UPLC, improve in three areas: “speed, resolution, and sensitivity”. In this system uses fine particles (less than 2.5µm) so decreases the lengh of column, saves time and reduces solvent consumption.
Ultra Performance Liquid Chromatography.
Spectrophotometric Method for Determination of Escitalopram Oxalate from Tablet Formulations.
A simple, rapid, accurate and precise assay procedure based on Spectrophotometric method has been developed for the estimation of Escitalopram oxalate (ESC) in Pharmaceutical formulation. The method was based on the bromination of ESC with a known excess amount of bromate-bromide mixture in acid medium followed by the determination of surplus bromine by reacting with dye methyl orange and measuring the absorbance at 507 nm. The proposed method was linear over the range of 2-14 µg/mL with the correlation co-efficient (r) of 0.9983 and the mean recovery for ESC was 100.5 %. The intermediate precision data obtained under different experimental setup, the calculated value of co-efficient of variance (CV, %) was found to be 1.14% for both day to day and within a day variation. The proposed method can be successfully applied for the analysis of tablet formulations.
Spectrophotometric Method Development for Estimation of Aceclofenac in Phosphate Buffer Dissolution Media
A simple, rapid and much economic spectrophotometric method in ultraviolet region has been developed for determination of aceclofenac in bulk and in pharmaceutical formulations. Aceclofenac has its absorption maxima at 273.2 nm in phosphate buffer. The linearity was observed in the concentration range 5-40 mcg/ml with correlation coefficient 0.9992. The same method was applied for the estimation of drug in a tablet dosage form and found to be feasible and reproducible. The method is found to be compatible with dissolution media as the UV cutoff for phosphate buffer is <200 nm. The proposed method was validated statistically as per ICH guidelines and found to be accurate and reproducible for the routine dissolution testing of aceclofenac in pharmaceutical dosage form.
Bio-analytical Estimation of Losartan and Losartan Carboxylic acid Concentrations in Human Plasma by Using LC-MS/MS.
Losartan, is highly effective blood pressure lowering agent, which directly works by selectively blocking angiotensin-I (AT-I) receptor. It is primarily metabolized in active form, Losartan carboxylic acid (LCA). A sensitive and selective LC-MS/MS method for the determination of Losartan and Losartan Carboxylic Acid in human plasma was developed and validated. The ammonium formate: methanol (50:50 V/V) buffer was selected as the mobile phase; as the retention time was about only 1 minute and valsartan was taken as internal standard, due to resemble structural and chemical nature with the Losartan. The results were reproducible and precise with the samples prepared by solid phase extraction technique using “OASIS” HLB Cartridges (30mg), during method development trials; therefore it was used in sample preparation, for whole bioanalytical study of Losartan. The limit of quantification was from 25 ng/ml to 1500 ng/ml.
Formulation and Process Validation of Clopidogrel Bisulfate 300mg Tablet
The purpose of study is to formulate and process validation is to create a robust formulation and to validate all the critical parameters challenged in manufacturing process like dry mixing, blending, lubrication, compression, coating and packing. By comparing the results of above challenged parameters, it shown that all the results of three batch's had met the pre determine specification and FDA requirement. Finally by seeing the results we can say that the process followed was correct and are as per c GMP requirements.
A Comparative Study of Regulatory Registration Procedure of Nutraceuticals in India, Canada and Australia
"Nutraceuticals” are the combination of Nutrition and pharmaceutical. The term Nutraceutical was given by Dr. Stephen in 1989. A dietary supplement is a product taken by mouth that contains a dietary ingredient (Vitamins, Minerals, Herbs, Amino acids etc.) Numerous definitions and nomenclature for dietary supplements exist worldwide. In India Food Safety and Standards authority (FSSA), defines Nutraceuticals as “foods for special dietary uses or functional foods or health supplements". In Canada Nutraceuticals are known as Natural health Products. In Australia, traditional, herbal, natural and alternative medicines and remedies are referred to as 'complementary medicines'. Every country has their own guidelines, regulatory requirements which deal with regulatory registration procedures of Nutraceuticals. In order to enter the Indian nutraceutical market, some of the very important areas of focus include product evaluation, actual product analysis, procuring licenses and developing India specific health and label claims. In Canada Product licensing, Site licensing, GMP, Adverse drug reporting, Clinical trials & Health claims. And in Australia Product licensing, GMP, Site licensing, Labelling & Helath claims are required.
Registration procedure of Nutraceuticals in India
Regulatory requirement of Nutraceuticals in different countries
UV Spectrophotometric Estimation of Satranidazole in Periodontal Gels
A simple, precise and economical UV method has been developed for the estimation of Satranidazole in periodontal gels. Satranidazole has the absorbance maxima at 319 nm in McIlvaine buffer pH 6.6.Beer's law was obeyed in the range 1-40µg/ml with correlation coefficient (n = 6) ≥ 0.9996.The proposed methods were successfully applied for the simultaneousdetermination of Satranidazolein gel dosage form. The developed method was validated for accuracy and precision. Percent recovery for Satranidazole was found in the range of 98.14% to 100.68 %. A high percentage recovery indicates the high accuracy of the method. This method has the advantage of quicker turnaround time of sample analysis and less cost involved. It can act as an alternative for HPLC method for the routine use in quality control laboratories of pharmaceutical industry for estimation of Satranidazole.
Certification Schemes and Marks: A New Mandate for Quality Assurance of Food and Drugs
Quality products are the demand of the day and the consumers have become more aware about their health and health related products. To develop a high degree of confidence about the safety and efficacy of medicines and food, specially packaged or processed food available in the market, various certifying agencies are involved. They issue quality “certificates”, “marks”, “logos” or “symbols to the product after evaluating certain quality parameters developed and validated by them. Presently, one can see many certification schemes existing for drugs like “Product Certification Scheme" by Bureau of Indian Standards (BIS), “Good Manufacturing Practices (GMP) Certification Scheme" by World Health Organization (WHO), “Premium Mark” and “Standard Mark" by Department of Ayurveda, Yoga and Naturopathy, Unani, Sidha and Homeopathy, and “Fruits Product Order (FPO) Mark” and “Organic certifications” for food products. This paper shall discuss various certification schemes and marks for food and drugs across the globe and their role in assuring quality.
Development and Characterization of Ketoprofen Loaded Protransfersome by Using Sodium Cholate for Transdermal Delivery
The study was aimed to characterize protransfersome gel as TDDS of ketoprofen for effective and sustain deliver of drug. The various formulation parameters were optimized by preparing 9 formulations using Sodium cholate as edge activator. All protransfersome formulations were characterized and found that, in physical appearance protransfersome gel was Yellowish semisolid compact mass and the mean particle size of transfersome varied from 1027-1209 nm. TEM micrographs transfersome suspension showed that the vesicles have a uniform spherical shape with a smooth surface. The formulation PTC3-I have higher rate to produce transfersome than all formulations (10.331±0.221) X 103. Formulations with cholesterol have good entrapment capacity and formulations with isopropanol have a little advantage of higher entrapment in comparison with others either with butanol or ethanol. Release rate study through cellophane membrane indicate that the % cumulative release in 48 hr was found ranging in 34%-64%, PTdC3-I formulation has shown highest percentage release.
Process Validation of Oral Solid Dosage Form-Tablet containing Anti Tubercular Agent
The purpose of study is to validate process of Rifampin 150mg and Isoniazid 75mg tablet and to create a robust formulation. The critical process parameter was identified with the help of optimization batches of process capability and evaluated by challenging specification. Three process validation batches of same size, manufacturing process, equipment & validation criteria was taken. The critical parameter involved in sifting, dry mixing, preparation of granulating agent, wet mixing, wet milling, drying, sizing, lubrication and compression stages were identified and evaluated. The outcome indicated that this process validation data provides high degree of assurance that manufacturing process produces product meeting its predetermined specifications and quality attributes.
Processing and Submission of Drug Master File; A Review
A Drug Master File is a confidential document used to provide detailed information about facilities, processes or articles used in the manufacturing process, packaging and storing of one or more human drug. The Drug Master File may be utilized either by the holder who establishes the file, or by one or more additional parties in support of their application. The Drug Master File filing allows a firm to protect its intellectual property from its partner while complying with regulatory requirements for disclosure of processing details. The review includes various types of Drug Master Files, the important aspects in filing and processing.
A Review on GC-MS and Method Development and Validation
Gas chromatography-mass spectrometry (GC-MS) is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Analytical methods development and validation play important roles in the discovery, development and Manufacture of pharmaceuticals. Method development is the process of proving that an analytical method is acceptable for use to measure the concentration of an API in a specific compounded dosage form which allow simplified procedures to be employed to verify that an analysis procedure, accurately and consistently will deliver a reliable measurement of an active ingredient in a compounded preparation. The analytical method validation is essential for analytical method development and tested extensively for specificity, linearity, accuracy, precision, range, detection limit, quantization limit, and robustness. In summary, analytical method development and validation allows to confirm that an accurate and reliable potency measurement of a pharmaceutical preparation can be performed.
Quality by Design (QbD) : A new concept for development of quality pharmaceuticals
Quality by Design (QbD) has become a new concept for development of quality pharmaceutical products, It is an essential part of the modern approach to pharmaceutical quality, QbD is a best solution to build a quality in all pharmaceutical products but it is also a major challenge to the Pharmaceutical industry whose processes are fixed in time, despite inherent process and material variability, Under this concept of QbD throughout designing and development of a product, it is essential to define desire product performance profile [Target product Profile (TPP), Target Product Quality Profile (TPQP)] and identify critical quality attributed (CQA). On the basis of this we can design the product formulation and process to meet the product attributes. This leads to recognise the impact of raw materials [critical material attributes (CMA)], critical process parameters (CPP) on the CQAs and identification and control sources of variability. QbD is an emerging idea which offers pharmaceutical manufacturer with increased self-regulated flexibility while maintaining tight quality standards and real time release of the drug product, This paper discusses the pharmaceutical QbD and describes how it can be used to develop the pharmaceutical products well within the specified period of time.