Qualimetric analysis of proton pump inhibitors in Ukraine.

OBJECTIVE: Introduction: On the pharmaceutical market of Ukraine, there are six international non-proprietary names of proton pump inhibitors (PPIs) - Omeprazole, Pantoprazole, Lansoprazole, Rabeprazole, Esomeprazole, Dexlansoprazole, which differ in a number of pharmacokinetic and pharmacodynamic parameters, safety profile, range of dosage forms and their cost. The aim: To investigate the competitiveness of proton pump inhibitors registered in Ukraine by comparing the parameters of their quality properties using the method of qualimetric analysis. PATIENTS AND METHODS: Materials and methods: Qualimetric analysis is based on the deductive-axiomatic approach, which allows quantifying the qualitative properties of drugs and determining the degree of competitiveness of each of them in the pharmaceutical market of Ukraine. The qualitative properties of PPIs in terms of consumer are efficacy, safety, convenience of use and cost. The subject of the study was 133 trademarks of PPIs registered in Ukraine. RESULTS: Results: The highest qualimetric values were obtained by omeprazole (Kk = 0.73) and its S-isomer esomeprazole (Kk = 0.66). Pantoprazole was inferior to them to a certain extent (Kk = 0.64). Lansoprazole (Kk = 0.53), rabeprazole (Kk = 0.50) and dexlansoprazole (Kk = 0.44) had the lowest values of the quality indices. CONCLUSION: Conclusions: According to the results of the study of the PPIs' competitiveness for parameters characterizing efficacy, safety, convenience of use and cost, assessed by qualimetric analysis, it has been established that the most completely and qualitatively satisfying consumer's needs are omeprazole and its S-isomer, esomeprazole.

Erroneous formulation of delayed-release omeprazole capsules: alert for importing countries.

BACKGROUND: Poor drug quality is a matter of serious concern, especially in countries where drug regulation and law enforcement are constrained by limited resources. This study was carried out to investigate the cause of quality failure of omeprazole in Cambodia in 2010 and Myanmar in 2014. METHODS: We conducted pharmacopoeial quantity, content uniformity and dissolution tests of 156 samples of omeprazole capsules collected in Cambodia in 2010 and Myanmar in 2014. High failure rates were found, especially in dissolution testing, and detailed investigation of several unacceptable samples was carried out by means of in-vitro dissolution profiling, scanning electron microscopy (SEM) and X-ray computed tomography (X-ray CT) to identify the cause of failure. RESULTS: Dissolution profiling with and without the acid stage showed that acid caused premature omeprazole release, indicating that the enteric coating of the omeprazole granules was ineffective. SEM examination of two failed samples revealed cracked and broken granules mixed with apparently intact omeprazole granules in the capsule. X-ray CT examination indicated that some granules of failed samples completely lacked enteric coating, and others had incomplete and non-uniform enteric coating or malformation. CONCLUSIONS: Omeprazole capsules collected in Myanmar and Cambodia showed high failure rates in pharmacopoeial tests, especially dissolution tests. Some samples were found to have ineffective or absent enteric coating of the granules, resulting in premature dissolution and degradation in acidic conditions. This is a potentially serious public health issue that needs to be addressed by regulatory authorities in Cambodia and Myanmar, possibly through a collaborative initiative with manufacturers.

Precision improvement for omeprazole determination through stability evaluation.

A new spectrofluorimetric method for the determination of omeprazole (OMP) based on its degradation reaction catalyzed by ultraviolet (UV) light is proposed. OMP in aqueous solution is very unstable, which renders a serious difficulty for controlling its quality. It does not show native fluorescence, but when exposed to UV radiation, it generates a highly fluorescent degradation product with adequate stability for indirect OMP quantification. Under the studied optimal experimental conditions (pH, temperature, exposure time to UV radiation), a specific rate constant of 2.851 min⁻¹--described by zero-order kinetic--was obtained for the degradation reaction. Using λ(exc) 293 nm and λ(em) 317 nm, a linear relationship was obtained (r² 0.9998) in the concentration range of 0.1 to 1.3 µg mL⁻¹, with a detection limit of 1.07 10⁻³ µg mL⁻¹ (S/N = 3). The methodology developed was successfully applied to OMP quality control in pure drugs and tablet dosage forms without previous treatment, with good tolerance to common excipient, and a high level of concordance between the nominal and experimental values. This work constitutes an important contribution to knowledge of the degradation mechanism of OMP. It has been shown to be appropriate for OMP quality control, to have an adequate sampling rate, low cost instrument, and to be a less polluting procedure.

Identifying, evaluating, and controlling bioanalytical risks resulting from nonuniform matrix ion suppression/enhancement and nonlinear liquid chromatography-mass spectrometry assay response.

Matrix ion suppression/enhancement is a well-observed and discussed phenomenon in electrospray ionization mass spectrometry. Nonuniform matrix ion suppression/enhancement across different types of samples in an analytical run is widely believed to be well compensated for by using a stable isotope-labeled internal standard (SIL-IS) in bioanalysis using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Therefore, the risk of nonuniform matrix ion suppression/enhancement is usually deemed low when an SIL-IS is used. Here, we have identified, evaluated, and proposed solutions to control bioanalytical risks from nonuniform matrix ion suppression/enhancement even with an SIL-IS through a case study using omeprazole. Two lots of human blank urine were tested, and ion enhancement of about 500% for omeprazole was observed in one lot but not in the other. When a quadratic regression model had to be used, the assay failed the industry acceptance criteria due to unacceptable positive bias for the middle and high quality control (QC) samples. The failure was attributed to different extents of matrix ion enhancement between the standards (STDs) and QCs, which resulted in the misaligned results from the regression model. It was concluded that, for the same amount of drug, nonuniform ion enhancement for different types of samples (STD or QC) resulted in different ion intensities, therefore leading to different response behaviors (linear or nonlinear) at the mass spectrometer detector. A simplified mathematical model was used to evaluate the risk when unmatched response models occurred for different types of samples. A diagnostic factor Q (Q = X(ULOQ)(-A/B)) was proposed to monitor the risks, where X(ULOQ) is the upper limit of quantitation of the assay, A is the quadratic slope of the curve, and B is the linear slope of the curve. The potential maximum errors were estimated on the basis of the mathematical model for different scenarios, and Q values were given to control the risks under these conditions for bioanalysis using LC-MS/MS.

Variabilidad en la medición de la calidad de prescripción por comunidades autónomas / Variability in the measurement of the pharmaceutical prescription quality by autonomous communities

ObjetivoConocer cómo se mide la calidad de la prescripción farmacológica y los indicadores utilizados en las diferentes comunidades autónomas (CC. AA.) del estado español.DiseñoEstudio descriptivo transversal.ÁmbitoNacional, en 17 CC. AA. del territorio español durante el período de enero a diciembre de 2007.MedicionesDefinición y tipos de indicadores de prescripción, unidades de medida.ResultadosSe ha obtenido información de 16 de las 17 CC. AA. a través de los servicios de salud autonómicos. Todos los servicios de salud han desarrollado un programa de evaluación de la prescripción farmacéutica. El número de indicadores varía entre 3 y 22. Los indicadores de selección son los más utilizados. Nueve de las 16 CC. AA. trabajan con indicadores de utilización y solo el País Vasco y Cantabria introducen indicadores de adecuación terapéutica. La medición se realiza en envases en 9 CC. AA. y en dosis diarias definidas en las 7 restantes. Los indicadores que más se repiten son porcentaje de nuevos fármacos, en 15 CC. AA. (93%), omeprazol frente al total de inhibidores de la bomba de protones, en 13 CC. AA. (81,2%), porcentaje de genéricos en 11 CC. AA. (68,7%) y antinflamatorios de elección en 10 CC. AA. (62%).ConclusiónCada servicio de salud autonómico desarrolla un programa de medición de la calidad de prescripción con indicadores propios y existe una gran variabilidad entre las diferentes CC. AA. Es necesaria una política común de calidad de la prestación farmacéutica para favorecer los procesos de benchmarking, comparar resultados, fomentar la investigación y promover la cooperación entre los servicios de salud(AU)

AimTo examine how the different Spanish health regions are evaluating pharmaceutical prescription quality and the type of prescribing indicators used.DesignCross-sectional study.SettingThe 17 Spanish Autonomous Communities during the period from January to December 2007.MeasurementsDefinition and type of prescribing indicators, measurement units.ResultsWe obtained information from 16 of the 17 CCAA through their health services. All health services had developed quality indicators of drug prescription. The number of indicators varied from 3 to 22 between regions. Most of the regions are using indicators based on adequate selection of drugs. Nine of the 16 CCAA are also including prevalence indicators and only the Basque Country and Cantabria are using indicators based on the quality of the therapeutic process. Nine CCAA use the number of packs as measurement unit and the other seven CCAA measure prescriptions in defined daily doses (ddd). The indicators most frequently used are: percentage of new drugs in 15 CCAA (93%), omeprazole in total IBP drugs in 13 (81.2%), percentage of generic drugs in 11 (68.7%) and selection of NSAID in 10 (62%).ConclusionEach regional health service has developed its own set of drug prescription quality indicators. Consequently, there is great variability between regions in the assessment of the quality of drug prescription. Common indicators are needed in order to establish a benchmarking process between regional health services(AU)

Generic omeprazole delayed-release capsules: in vitro performance evaluations.

BACKGROUND: After the patent on omeprazole delayed-release capsules expired, Food and Drug Administration (FDA) approved several generic omeprazole delayed-release capsule applications. FDA has received some complaints concerning a lack of therapeutic effect of the generic omeprazole delayed-release capsules. AIM: To investigate the quality of five different marketed generic omeprazole delayed-release capsules. METHOD: The dissolution characteristics of these generic omeprazole delayed-release capsules were determined according to the United States Pharmacopeia (USP). Additional dissolution studies under simulated in vivo physiological conditions were also conducted to determine whether generic omeprazole capsules would perform similarly under these conditions. RESULTS: The experimental data show that all the generic omeprazole delayed-release capsules met the USP standards. The in vitro dissolution of generic drugs is similar to that of the brand omeprazole product. CONCLUSIONS: There is no scientific evidence to support the claims that the generic omeprazole delayed-release capsules perform differently from the brand omeprazole product in vitro.

Quantification of tenatoprazole in rat plasma by HPLC: validation and its application to pharmacokinetic studies.

A simple, reliable HPLC method with UV detection (295 nm) in rat plasma was developed and validated for quantification of tenatoprazole, a novel proton pump inhibitor, which is in clinical trials. Following a single-step liquid-liquid extraction, the analyte and internal standard were separated using an isocratic mobile phase on a reverse phase C(18) column. The lower limit of quantitation was 20 ng/mL, with a relative standard deviation of less than 10%. A linear dynamic range of 20-6000 ng/mL was established. This HPLC method was validated with between-batch and within-batch precision of 2.9-6.3 and 1.4-5.8%, respectively. The between-batch and within-batch accuracy was 95.1-104.1 and 92.4-101.0%, respectively. This validated method is simple and repeatable enough to be used in pharmacokinetic studies.

Validation of chromatographic methods: evaluation of detection and quantification limits in the determination of impurities in omeprazole.

To guarantee that an analytical procedure gives reliable, exact and interpretable information about a sample, it must be validated. Two ambiguous parameters are detection limit and quantification limit. The determination of these limits is still of great concern and there are still a variety of procedures described in the current literature. The fundamental objective of the present work is to apply the different recommendations suggested by official guidelines for the quantitative determination of omeprazole and its impurities (omeprazole sulphone and 5-hydroxy-omeprazole) in capsules and tablets using high performance liquid chromatography with UV detection. The importance of calibration linearity in the context of the quantification limit is considered, since one of the approaches, the estimated concentrations of this limit, are deduced from the regression line. The values of the detection limit and the quantification limit obtained show that, in chromatographic analyses, the best method is that based on the use of the parameters obtained from the analytical curve, which are statistically reliable. It was shown that smaller values of the detection limit and the quantification limit were obtained by the visual approach and by the method using the signal-to-noise ratio. However, these values may reflect a subjective evaluation, prone to error and large variations. This was confirmed by showing that these methods result in values that fall outside the linear range of the method.

Assessment of the pharmaceutical quality of omeprazole capsule brands marketed in Egypt.

The pharmaceutical quality of 7 local omeprazole capsule brands in Egypt was assessed relative to the proprietary product (Losec). Drug content, content uniformity, drug release (using USP test for enteric coated articles and a modified release test) were determined. Products were subjected to a 3-month stability study. Of the 7 brands, 6 had satisfactory drug content and content uniformity. All brands passed the USP drug release test. The modified release test proved to be more discriminative. After 3 months storage, drug content of 3 brands remained > 90% and 2 of these brands maintained drug release above 75%. Changes in pellet appearance during storage were indicative of omeprazole chemical degradation.

Determination of lansoprazole in pharmaceutical capsules by flow injection analysis using UV-detection.

The direct determination of lansoprazole by using a flow injection analysis (FIA) with UV-detection and its application to the pharmaceutical capsules is described, in this study. The best carrier solvent was found to be 0.01 M NaOH and it was determined at optimum conditions such as flow rate of 1 ml min(-1) and wavelength of 292 nm. Examining the repeatability of the method that was found to be 1.72% for intra-day and 2.13% for inter-day precision using the 8.01 x 10(-6) M lansoprazole concentration has validated the method. The linear range of the method was 5.4 x 10(-6) to 5.4 x 10(-5) M. The limit of detection and quantification was found to be 5.8 x 10(-7) and 1.7 x 10(-6) M, respectively. The proposed method was applied to the pharmaceutical capsules and very good results obtained. Thus, the FIA method for the quantification of lansoprazole can be proposed as a cheap, rapid, easy, accurate, and precise method for the routine determination in pharmaceutical preparations.

Switching omeprazole in Sweden and the United States.

This article compares the Swedish Medical Products Agency's (MPA) decision to switch omeprazole from prescription (Rx) to over-the-counter (OTC) status with the US Food and Drug Administration (FDA) advisory panel's decision not to authorize the switch. The agencies' differing perspectives on efficacy, safety, labeling, and clinical trial requirements are evaluated with regard to the Rx-to-OTC switch process in general and omeprazole's case in particular. The FDA and MPA regulatory policies on switches are substantially divergent. The FDA maintains a stricter set of switch guidelines and requirements than the MPA. One could infer from this that the FDA is more risk-averse than the MPA. Nevertheless, the omeprazole switch in Sweden appears to be an exception in that it contrasts with the MPA's historical reluctance to switch the Rx status of medications. Cost considerations appear to have triggered the omeprazole switch, making it a special case. The lessons to be drawn from this case study are both specific and general. At the specific level, this case study suggests the MPA's decision to switch omeprazole was prompted by economic considerations, whereas the FDA's mandate did not allow cost to affect its decision on omeprazole. At a general level, this case study indicates that the differences between the FDA and MPA with respect to their regulatory policies on switches and their mandates apply not only to omeprazole but also to the dozens of switches currently under consideration by the respective regulatory agencies.

In vitro evaluation of dissolution properties and degradation products of omeprazole in enteric-coated pellets.

This report describes results of an in vitro study in which capsules containing omeprazole in enteric-coated pellets from different Brazilian manufacturers were evaluated. The original product was the reference in comparison to three similar products (A, B, and C). Samples were submitted to severe conditions (40 degrees C and 75% relative humidity during 120 days), and the tests performed were the omeprazole content, the percentage of omeprazole dissolved from the pellets, and the amount of H 238/85, its main degradation product. The data obtained suggest that these products could not be considered interchangeable. Differences in physical and physicochemical properties of products A, B, and C indicated that they did not maintain the required stability and that bioavailability might be affected by the poor dissolution of omeprazole from the pellets.