STABILITY INDICATING CHROMATOGRAPHIC METHODS FOR THE DETERMINATION OF PHARMACEUTICAL DOSAGE FORMS CONTAINING CALCIUM DOBESILATE IN THE PRESENCE OF ITS INTERFERING SUBSTANCES

Objective: Two simple, accurate and precise chromatographic methods were developed for the determination of calcium dobesilate in the presence of its interfering substances as its degradation product and/or impurity hydroquinone in pharmaceutical dosage forms with lidocaine hydrochloride alone or in combination with dexamethasone acetate. Methods: The first method is HPTLC-spectrodensitometric one using benzene: methanol: ethyl acetate: ammonia: sodium lauryl sulphate (7: 2.1: 2.5: 0.1: 0.05 v/v/v/v/w) as a developing system and scanned at 220 nm. Second one is an HPLC method where the mixture was separated on an ODS-3 C18 column with flow rate 1 ml/min and the mobile phase was phosphate buffer: acetonitrile (35:65 v/v) (adjusted to pH 3.4 with o- phosphoric acid), scanned at 220 nm. Results: The robustness of the method was determined to assess the effect of small but deliberate variation of the chromatographic conditions on the determination of cited drugs in a presence of interfering substances. Robustness was determined by changing the mobile phase flow rate to 0.5, 1,and 1.5 mLmin−1, pH to 3.5, 4, and 5, and the concentration of acetonitrile in the mobile phase to 60% and 80%. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations containing the cited drugs and were validated via ICH guidelines. Conclusion: The proposed methods could be used for the routine analysis of the cited drugs in their pharmaceutical formulation in quality control laboratories

Comparative study of the resolution efficiency of HPLC and HPTLC-densitometric methods for the analysis of mebeverine hydrochloride and chlordiazepoxide in their binary mixture

Accurate, rapid, and selective reversed phase HPLC and HPTLC-densitometric methods with UV detection have been developed and validated for simultaneous determination of a binary mixture of mebeverine hydrochloride (MVH) and chlordiazepoxide (CDZ) in their Co-formulation. For the HPLC method, ACE-126-2546 AQ C-18 column, (250×4.6 mm i.d., 5 μm particle size) in isocratic mode, with mobile phase containing 25 mM ammonium acetate buffer: acetonitrile in the ratio of (60:40, v:v), pH adjusted to 3±0.2 by using hydrochloric acid, the flow rate of 1.0 mL/min and detection was performed at 260 nm. The retention times were 7.23±0.01 and 3.85±0.01 min for MVH and CDZ, respectively. For the HPTLC-densitometric method, the separation was performed using stationary phase pre-coated silica gel 60F254 and mobile phase ethyl acetate: methanol (8:4, v:v) were used and scanned at 222 nm with Camag TLC scanner controlled by Wincats Software. The Rf values were 0.26±0.02 and 0.73±0.01 for MVH and CDZ, respectively. The linearity graphs for MVH and CDZ, respectively, were found to be linear over 1-50 μg/mL and 0.5-40.0 μg/mL with mean percentage recoveries 100.14±0.354 and 99.70±0.764 for HPLC method and 0.5-30.0 μg/band and 1-14 μg/band with mean percentage recoveries 100.29±0.665 and 99.68±0.987 for HPTLC-densitometric method. A comparative study of different analytical validation parameters such as accuracy, precision, specificity, robustness was conducted. The obtained results were statistically compared with those of the official methods; using student t-test, F-test, and one way ANOVA, showing no significant difference with respect to accuracy and precision

Simultaneous determination of Simvastatin and Sitagliptin in tablets by new univariate spectrophotometric and multivariate factor based methods

Five simple, sensitive and precise spectrophotometric and chemometric methods were used for simultaneous determination of Simvastatin (SM) and Sitagliptin (SIT) in their pure powdered forms and in the tablets. The proposed methods are the extended ratio subtraction method (EXRSM), ratio difference method (RDSM), mean centering of ratio spectra method (MCR) and chemometric methods, namely principal component regression (PCR) and partial least squares (PLS). In EXRSM; SM was determined at 237.5 nm, while SIT was determined at 267 nm, in RDSM; the difference in amplitudes at 237.5 and 245.5 nm was used for SM and 263.5 and 248.0 nm for SIT, while in MCR; SM and SIT were determined at 239.0 and 273.0 nm, respectively. PCR and PLS are factor based multivariate methods which utilize the whole spectra of SM and SIT. The developed methods were successfully applied for the determination of the studied drugs in their bulk powder, laboratory prepared mixtures and in tablets. All validation parameters of the developed methods were determined. The obtained results were statistically compared with each other along with a reported method

Stability Indicating Spectrophotometric Methods Determination of Nicardipine in the Presence of its Alkaline Induced Degradation Products

Objective: Derivative, ratio spectra derivative and ratio difference spectrophotometric methods were developed and validated for simultaneous determination of Nicardipine (NIC) in the presence of its alkaline induced degradation products. Methods: In these methods the overlapped spectra of NIC and its alkaline induced degradation products were well resolved by measuring the amplitudes of first derivative (D1) spectra and the second derivative (D2) at 382.3 and 239 nm, respectively. NIC was determined by ratio spectra derivative by measuring the amplitude at 244 nm. The ratio difference spectrophotometric method was developed in which the difference between amplitudes at 237.5 nm and 260 nm of the ratio spectra were recorded. The linearity range for the applied methods was 2-18 μg/ml.Results: All the developed methods were validated according to ICH Guidelines, NIC was determined with acceptable accuracy and precision.Conclusion: These methods were suitable as stability indicating methods for the determination of NIC in the presence of its alkaline induced degradation products either in bulk powder or in a pharmaceutical formulation. Statistical analysis of the results with those obtained by applying a reported method has been carried out revealing high accuracy and good precision.Keywords: Nicardipine, Spectrophotometry, Pharmaceutical preparations, Stability indicating, derivative, ratio derivative and ratio differenc

SELECTIVE LIQUID CHROMATOGRAPHIC QUANTIFICATION OF BETAMETHASONE VALERATE AND CLIOQUINOL IN PRESENCE OF POTENTIAL INTERFERENTS

Objective: To develop and justify a validated simple and selective RP-HPLC method for simultaneous determination of betamethasone valerate (BETA), clioquinol (CLIO) together with their potential interferents including their proposed degradation products, the preservatives methyl paraben (MPB) and propyl paraben (PPB) as well as gentamycin and tolnaftate. Methods: Degradation products of betamethasone and clioquinol were prepared then the technique was built using an efficient chromatographic separation on a Zorbax C18 column (25 cm×4.6 mm, 5.0 μm) using water- methanol-acetonitrile- glacial acetic acid (394: 50: 550: 6, v/v/v/v) as mobile phase and the eluent was monitored at 275 nm. Results: The developed method was linear over the concentration ranges of 12-240 mg mL-1, 30-3000 mg mL-1, 7-140 mg mL-1 and 3.5-70 mg mL-1 forBETA, CLIO, MPB and PPB, respectively, with high degree of accuracy and precision. Conclusion: The method was successfully applied for the analysis of BETA and CLIO in their pharmaceutical preparations and their combined formulation with gentamycin and tolnaftate. Recoveries were quantitative, and the results obtained agreed with those obtained by official methods

Smart Spectrophotometric Methods for Concurrent Determination of Furosemide and Spironolactone Mixture in Their Pharmaceutical Dosage Forms

Simple, precise, accurate and specific spectrophotometric methods are progressed and validated for concurrent analysis of Furosemide (FUR) and Spironolactone (SPR) in their combined dosage form depend on spectral analysis procedures. Furosemide (FUR) in the binary mixture could be analyzed at its λmax 274 nm using its recovered zero order absorption spectrum using constant multiplication method (CM). Spironolactone (SPR) in the mixture could be analyzed at its λmax 238 nm by ratio subtraction method (RS). Concurrent determination for FUR and SPR in their mixture could be applied by amplitude modulation method (AM), absorbance subtraction method (AS) and ratio difference (RD). Linearity ranges of FUR and SPR were (2.0µg/mL-22.0 µg/mL) and (3.0µg/mL-30.0 µg/mL), respectively. Specificity of the proposed spectrophotometric methods was examined by analyzing the prepared mixtures in laboratory and was applied successfully for pharmaceutical dosage form analysis which have the cited drugs without additives contribution. The proposed spectrophotometric methods were also validated as per as the guidelines of ICH. Statistical comparison was performed between the obtained results with those from the official methods of the cited drugs, using one-way ANOVA, F-test and student t-test. The results are exhibiting insignificant difference concerning precision and accuracy

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially