DEVELOPMENT AND VALIDATION OF RPLC METHODS FOR PURITY CONTROL OF SELECTED ANTIBIOTICS

nrpages: 143status: publishe

Formulation and Optimization of Monolithic Fixed-Dose Combination of Metformin HCl and Glibenclamide Orodispersible Tablets

The treatment of type II DM involves the use of combination of drugs, especially at the chronic stage. However, the pill burden of this combination therapy combined with swallowing difficulties, occurring at a later stage of DM, has been the major challenge for successful treatment outcomes. This study was aimed at formulating and optimizing a monolithic fixed-dose combination (FDC) of metformin (MET) and glibenclamide (GLB) orodispersible tablets (ODTs) to overcome both the pill burden and swallowing problems. The FDC ODTs were prepared by the melt granulation technique using polyethylene glycol (PEG) 6000 as a binding agent and crospovidone as a superdisintegrant. In the preliminary study, the effects of sodium lauryl sulphate (SLS), PEG 6000, crospovidone, and compression force on friability, disintegration time, and drug release of tablets were investigated. The FT-IR studies showed that there were no incompatibilities between MET and GLB as well as within excipients. The preliminary studies revealed that PEG 6000 and compression force significantly affect both the friability and the disintegration time, while SLS and crospovidone only affect the disintegration time. Therefore, the effects of PEG 6000, crospovidone, and compression force were further studied and optimized using the central composite design. Accordingly, the most desirable optimal values were obtained at 3.82% of PEG 6000, 9.83% of crospovidone, and 10.6 kN compression force having a friability of 0.302% and a disintegration time of 18.7 seconds. From these results, it can be concluded that a monolithic FDC of MET and GLB ODTs having adequate mechanical strength and faster disintegration time was successfully formulated

Development and Validation of a High-Performance Liquid Chromatographic Method for the Determination of Cinitapride in Human Plasma

A precise and reliable reversed-phase high-performance liquid chromatographic method with ultraviolet detection was developed and validated to determine cinitapride in human plasma. After liquid-liquid extraction, chromatographic separation was achieved on a Nucleosil C18 (25 cm × 4.6 mm, 5 µm) column with an isocratic elution consisting of 10 mM ammonium acetate (pH 5.2), methanol, and acetonitrile, 40 : 50 : 10, v/v/v. The developed method was validated as per US FDA guidelines for its linearity, selectivity, sensitivity, precision, accuracy, and stability. Satisfactory findings were obtained from the validation studies. The linearity range of the method was 1 to 35 ng/mL while the extraction recovery of cinitapride in human plasma was more than 86%. The percent coefficient of variation of both intraday and interday precision was ≤7.1%

New RP-HPLC Method Development and Validation for Dorzolamide in Ophthalmic Dosage Form

A reversed phase liquid chromatographic method with UV detection at 254 nm for dorzolamide assay in ophthalmic solutions was developed and validated. Chromatographic separation was achieved on a Zorbax SB C18 (250 mm × 4.6 mm, 5 µm) column kept at 30°C with an isocratic mixture of mobile phase (phosphate buffer, pH 2.5, and acetonitrile, 90 : 10 v/v) at a flow rate of 0.8 mL/min. The method was validated for its specificity, linearity, accuracy, precision, limit of detection, limit of quantification, and robustness based on ICH guidelines. The validation studies revealed satisfactory results. The proposed method has been applied for the quantification of dorzolamide in commercial samples. The developed method is fast, simple, specific, accurate, and sensitive, hence can be applied for routine quality control analysis of dorzolamide in pharmaceutical dosage form

Development and validation of a liquid chromatographic method for purity control of clopidogrel–acetylsalicylic acid in combined oral dosage forms

A reversed phase liquid chromatographic method with UV detection for the simultaneous determination of clopidogrel and acetylsalicylic acid and their related substances in combined oral formulations was developed and validated. Good separation was achieved on a Luna C18 column (150 mm × 4.6 mm, 3 μm) using gradient elution at a flow rate of 1 mL/min and a column temperature of 35 °C. UV detection was performed at 220 nm. The validation was performed according to the ICH guidelines. The method proved to be specific, sensitive (LOQ=0.975 μg/mL and 0.0384 μg/mL for clopidogrel and acetylsalicylic acid, respectively), linear in the concentration range from LOQ to 325 μg/mL for clopidogrel and from LOQ to 650 μg/mL for acetylsalicylic acid, precise (RSD values for intermediate precision <1%) and accurate with mean recovery values of 100.7% and 100.2% for clopidogrel and acetylsalicylic acid, respectively. Moreover, the solution stability and method robustness were examined. The method gives satisfactory separation of impurities of clopidogrel and acetylsalicylic acid and so it is suitable for quantification of the related substances as well as for the assay of the actives.status: publishe

Infant Exposure to Metals through Consumption of Formula Feeding in Mekelle, Ethiopia

This study aimed at determination of heavy metals (cadmium, lead, and zinc) in milk-based infant formulas collected from Mekelle, Ethiopia, and their associated health risks to the infants through consumption of these products. The infant feeding samples were dry-ashed in a muffle furnace followed by digestion in nitric acid and the resulting solutions were analyzed by flame atomic absorption spectrophotometer. Cadmium was not detected in the samples while the levels of lead and zinc ranged from not detected value to 0.103 mg/kg and from 27.888 to 71.553 mg/kg, respectively. The estimated daily intake values and the health risk indices of both metals were below their respective safety limits and the threshold of 1, respectively. These findings show low infant health risk of these metals through consumption of these products. Nevertheless, regular monitoring of infant formula for toxic metals is required since infants are potentially more susceptible to metals

Analysis of Temocillin and Impurities by Reversed Phase Liquid Chromatography: Development and Validation of the Method

© 2014, Springer-Verlag Berlin Heidelberg. A robust, specific, precise and sensitive high-performance liquid chromatographic method has been described for purity control of temocillin. Chromatographic separation was achieved using a Symmetry C18 (150 × 4.6 mm, 5 µm) column kept at 30 °C. The mobile phase consisted of a gradient mixture of mobile phases A (5 g/L solution of Na2HPO4·2H2O, pH 7) and B (ACN-MeOH-H2O, 50:10:40 v/v/v) pumped at a flow rate of 1.0 mL/min. UV detection was performed at 235 nm. The developed method was validated according to the ICH guidelines for its robustness, selectivity, sensitivity, precision and linearity. An experimental design was applied for the robustness study. Linearity was assessed both at impurity level in the range from LOQ to 10 % and assay level from 25 % to 150 % (0.6 mg/mL = 100 %). It is the first liquid chromatographic method described for the separation of temocillin and its potential impurities. It was possible to identify four degradation products from the forced degradation studies. The degradants do not interfere with the main peak and other known impurities showing that the method is specific and stability-indicating.status: publishe

Study of aldehyde oxidase with phthalazine as substrate using both off-line and on-line capillary electrophoresis

An optimized and economical capillary electrophoretic method for both off-line and on-line study of the enzyme aldehyde oxidase and its substrate phthalazine was developed. The separation of the substrate phthalazine and its metabolite 1-phthalazinone was achieved using micellar electrokinetic chromatography (MEKC) with sodium dodecyl sulphate in the background electrolyte (BGE). The BGE consists of 25 mM sodium phosphate buffer containing 50 mM sodium dodecyl sulphate at pH 7.4. A bare-fused-silica capillary with a capillary length of 40 cm, 50 μm ID and effective length of 30 cm was used to develop the capillary electrophoresis method. Improved separation conditions were elaborated and the separation method was validated based on the ICH and EMA guidelines. The limit of detection for phthalazine and 1-phthalazinone was 8 μM and 3 μM, respectively. The limit of quantification was 25 μM for phthalazine and 10 μM for 1-phthalazinone. The linearity of the detector response was checked for 1-phthalazinone at nine different concentrations in the range 10-500 μM and the determination coefficient was 0.9994. Accuracy was tested by comparing the corrected peak area of 1-phthalazinone reference solution at 20 μM and 50 μM with the corrected peak area of 20 μM and 50 μM 1-phthalazinone in the presence of human liver cytosol (HLC). Accuracy values of +5.3% and -2.5% were obtained at 20 μM and 50 μM, respectively. The on-line enzymatic reaction was successful with the application of the method of transverse diffusion of laminar flow profiles (TDLFP), which enables the mixing as well as separation of the enzyme and substrate inside the nanoliter-scale capillary. TDLFP is examined to be precise when performing 5 consecutive injections, with a relative standard deviation of 7.16% which is within the limitation of EMA standards. This miniaturized and low-cost incubation and separation method could be further introduced into industry and extended to other substrates.status: publishe

Development and Validation of a Fast Reversed Phase Liquid Chromatographic Method for the Analysis of Ethionamide in Dosage Forms

© 2018, Bentham Science Publishers B.V. All rights reserved. Background: Ethionamide (ETA) is widely used as one of the agents for the treatment of multidrug resistant tuberculosis. Although quality control is an important issue, a fast LC-UV method for the assay and impurity determination of ETA was lacking. So, the aim of this study was to develop such a method to evaluate drug products and follow up dissolution tests of ETA tablets. Methods: Chromatographic separation was achieved using a Hypersil BDS C18 (150 mm×4.6 mm, 3 μm) column kept at 30 °C. The mobile phase consisted of 300 mL of acetonitrile, 0.14 g of NH4 H2 PO4 and 700 mL of water pumped at a flow rate of 1.0 mL/min. UV detection was performed at 287 nm. The developed LC method was validated according to the ICH guidelines. Results: Validation results show that the developed LC method is specific, linear, sensitive, precise, accurate and robust. Forced degradation studies revealed that the generated degradation products did not interfere with ETA and known impurities, thus proving the specificity of the developed LC method for the assay of ETA tablets and quantification of impurities. Conclusion: A robust, selective, sensitive and fast LC method has been developed and validated for analysis of ETA and its main impurities in tablets.status: publishe

Characterization of mesoporous silica used for drug delivery by sorptive interaction - multiple headspace extraction-gas chromatography

A multiple headspace extraction experiment coupled to gas chromatography (MHE-GC) is used for the classification and qualification of different mesoporous silica (MPSi) materials used for drug delivery. In this MHE experiment, a pure liquid solvent probe is fully evaporated in a sealed headspace vial in the presence of the MPSi sample, leading to a gas-solid partitioning that is theoretically described. The obtained results matched with the known characteristics of the studied samples, such as adsorption capacity due to differences in porosity and passivation treatments. Moreover, it proves the effectiveness of a poly dimethyl siloxane (PDMS) coating treatment over a thermal one in reducing the specific interactions of the MPSi. In addition, it evidences the important role of confinement effects when the pore diameter is close to the microporosity range. Finally, a simple experiment for fast screening is proposed by comparison of the results obtained for four different probes used as a mixture.status: publishe