DISSOLUTION PERFORMANCE OF MELOXICAM FORMULATIONS UNDER HYDRODYNAMICS OF USP PADDLE APPARATUS AND FLOW-THROUGH CELL METHOD

Objective: To study the in vitro dissolution performance of four generic formulations of the poorly soluble drug meloxicam and the reference under hydrodynamic environments generated by flow-through cell method and USP paddle apparatus (pharmacopeial test). Methods: Dissolution method was validated according to ICH guidelines. Dissolution profiles were carried out with an automated flow-through cell apparatus (laminar flow at 16 ml/min with 22.6 mm cells) and USP paddle apparatus at 75 rpm. Phosphate buffer pH 7.5 at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 362 nm was carried out during 30 min. Dissolution profiles were compared with model-dependent and-independent methods. Results: Practically, all generic formulations showed significant differences with the percentage of drug dissolved at 30 min, mean dissolution time and dissolution efficiency, when USP paddle apparatus was used (*P<0.05), while only two generic formulations were different to reference using flow-through cell method. After adjustment to different mathematical equations, Weibull function was the best model to describe meloxicam dissolution performance and significant differences were found with all drug products when USP paddle apparatus was used, while only one formulation was different with flow-through cell method. Conclusion: The study reveals the need to look for better dissolution schemes for meloxicam tablets since USP paddle apparatus may not reflect properly the in vitro dissolution performance of meloxicam generic formulations and reference

IN VITRO EQUIVALENCE STUDY OF DIFFERENT DOSES OF CARBAMAZEPINE REFERENCE TABLETS USING USP APPARATUSES 2 AND 4

Objective: To perform an in vitro equivalence study of two doses of carbamazepine reference tablets sold in the local market under hydrodynamic conditions of USP Apparatus 4, a dissolution apparatus that better simulates the human gastrointestinal tract. Results were compared with dissolution official conditions using USP Apparatus 2. Methods: Dissolution profiles of both formulations were carried out with an automated USP Apparatus 2 at 75 rpm and 900 ml of dissolution medium. USP Apparatus 4 with laminar flow at 16 ml/min and 22.6 mm cells were used. 1% lauryl sulfate aqueous solution at 37.0±0.5 °C was used as dissolution medium. Spectrophotometric determination of drug at 285 nm was carried out during 60 min. Dissolution profiles were compared with model-independent and-dependent approaches. Results: When comparing dissolution profiles of low vs. high dose similar profiles were found (f2>50) in each dissolution apparatus, however, when the same dose was compared, USP 2 vs. USP 4, opposite results were obtained. Comparison of mean dissolution time and dissolution efficiency data corroborates these results. Weibull function was the best mathematical model that described the in vitro dissolution performance of carbamazepine. No significant differences were found in Td values (low vs. high dose) but opposite results were also found with USP 2 vs. USP 4. Conclusion: Equivalent dissolution performance of two doses of carbamazepine reference tablets were found in each USP dissolution apparatus. The main problem identified in this comparative study is the low dissolution rate and extent found with USP Apparatus 4. More research on this field is necessary for all available doses of reference drug products since the quality of generic formulations depends on the quality of references

INFLUENCE OF DOSE AND USP DISSOLUTION APPARATUS IN THE RELEASE PERFORMANCE OF REFERENCE TABLETS: PROPRANOLOL-HCl AND RANITIDINE-HCl CASES

Objective: Due to quality of generic formulations depends on available information of reference drug products the aim of this work was to perform an in vitro dissolution study of two doses of propranolol-HCl and ranitidine-HCl reference tablets using USP basket or paddle apparatus and flow-through cell method. Methods: Two doses of propranolol-HCl (10-mg and 80-mg) and ranitidine-HCl (150-mg and 300-mg) of Mexican reference products were used. Dissolution profiles of propranolol-HCl were obtained with USP basket apparatus at 100 rpm and 1000 ml of 1% hydrochloric acid. Profiles of ranitidine-HCl were determined with USP paddle apparatus at 50 rpm and 900 ml of distilled water. All formulations were also studied with the flow-through cell method using laminar flow at 16 ml/min. Dissolution profiles were compared by model-independent (f2 similarity factor, mean dissolution time and dissolution efficiency) and model-dependent methods (dissolution data adjusted to some mathematical equations). Time data, derived from these adjustments, as t50%, t63.25%, and t85% were used to compare dissolution profiles. Results: With all approaches used and being high solubility drugs significant differences were found between low and high doses and between USP dissolution apparatuses (*P<0.05). Conclusion: In vitro dissolution performance of two doses of propranolol-HCl and ranitidine-HCl was not expected. Considering the same USP dissolution apparatus, the reference tablets did not allow the simultaneous release of the used doses. The results could be of interest for pharmaceutical laboratories or health authorities that classify some drug products as a reference to be used in dissolution and bioequivalence studies

RAPID AND SIMPLE DETERMINATION OF IBUPROFEN AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

Objective: To develop a UV-derivative spectrophotometric method with zero-crossing determinations for the simultaneous quantification of ibuprofen (IBU) and caffeine (CAF) in fixed-dose combination formulations (soft gelatin capsules). The proposed method was validated, and it was applied to determine the in vitro dissolution performance of IBU and CAF from a commercial formulation. Methods: The method is based on the use of the second-derivatives of the zero-order spectra and measurement at zero-crossing wavelengths. Linearity, accuracy, precision, stability, and influence of the filter were evaluated. Dissolution profiles of IBU and CAF were obtained with the USP Apparatus 2 at 100 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4 as dissolution medium. Dissolution samples were treated with the proposed UV-derivative method and results were compared with data previously published. Results: The zero-crossing points for the determination of IBU and CAF were found at 235.6 nm and 218.8 nm, respectively. The method was linear in the range of 7.5-15 µg/ml for IBU and 5-25 µg/ml for CAF (R2>0.999, *P<0.05). The precision and accuracy of the method were within acceptable criteria (CV<0.99% and recovery 97.97% for IBU and CV<1.76% and recovery 99.05% for CAF). Fiberglass filters were the best option to filter samples and stability of all drugs was adequate when solutions were stored at 25 °C during 24 h. Dissolution of IBU and CAF at 60 min was 99-100% with dissolution profiles of sigmoidal S-shape. Weibull function and Logistic were the best-fit models that describe the in vitro dissolution performance of both drugs. Conclusion: The proposed UV-derivative method allows the simultaneous determination of IBU and CAF in fixed-dose combination formulations. The method generates reliable information that can be compared with published data. The proposed UV-derivative method is rapid and simple and can be easily adopted for routine analysis of IBU and CAF

COMPARATIVE DISSOLUTION STUDIES OF WARFARIN SODIUM TABLETS: INFLUENCE OF AGITATION RATE, DISSOLUTION MEDIUM, AND USP APPARATUS

Objective: The aim of this study was to carry out comparative dissolution studies with warfarin sodium reference tablets under the hydrodynamic environments generated by the USP basket and paddle apparatus and flow-through cell using different agitation rates and dissolution media. Methods: Dissolution profiles were obtained with the USP basket and paddle apparatus at 50, 75, and 100 rpm and 900 ml of water as dissolution medium. After this, dissolution profiles of warfarin sodium were obtained with the USP paddle apparatus and flow-through cell method using 0.1 N hydrochloric acid, acetate buffer pH 4.5, phosphate buffer pH 6.8, and water. Spectrophotometric determination at 308 nm was carried out during 30 min. Dissolution profiles were compared with model-independent and model-dependent approaches. Results: Significant differences were found with mean dissolution time and dissolution efficiency at 50 and 75 rpm (*P<0.05). Makoid-Banakar was the best-fit model used to describe the in vitro release performance of warfarin sodium with 50-100 rpm and the USP basket and paddle apparatuses. Significant differences in all calculated parameters were found (*P<0.05) excepting percent dissolved at 30 min with 0.1 N hydrochloric acid and phosphate buffer pH 6.8. Conclusion: More research is necessary to identify the in vitro release performance of poorly soluble drugs under available USP apparatuses considering factors as agitation rate and kind of dissolution media. The knowledge of the in vitro release performance of reference drug products is important for the design of better generic formulation

HPLC-PDA METHOD FOR THE QUANTIFICATION OF PARACETAMOL IN PLASMA: APPLICATION TO PK/PD STUDIES WITH ARTHRITIC RATS

Objective: To develop and validate an easy, rapid, sensitive and selective high-performance liquid chromatography with photodiode diode-array (HPLC-PDA) detection method for quantification of paracetamol and to demonstrate its application in a pharmacokinetic–pharmacodynamic study with arthritic rats.Methods: Paracetamol was separated from plasma samples (50-100 µl) by a single protein precipitation step, prior to HPLC-PDA detection. The separation was performed on a Knauer Eurospher II, C18 column 5 µm, 150 × 4.6 mm. The mobile phase comprised a mixture of water: methanol (75:25) and the flow rate was 1.1 ml/min. The detection wavelength was set at 245 nm. All analyses were carried out at room temperature (25 °C). Pharmacodynamics data were obtained with a gout-type pain model in rats.Results: The method was linear within a range of 0.2-200 µg/ml (R2≥0.99). The intra-day and inter-day precision and accuracy expressed as coefficient of variation and relative error, respectively were below 10%. The lower limit of quantification was 0.2 µg/ml. Plasma samples were stable at least for 5 w at ‒20° C.Conclusion: The validated method is sensitive, precise, accurate and specific as other more complex high-performance liquid chromatographic methods coupled to mass spectrometry (HPLC-MS), using small plasma samples (50-100 µl) and with a short time analysis (<5 min). The method was successfully applied to a pharmacokinetic-pharmacodynamic study of paracetamol in arthritic rats.Â

SIMULTANEOUS DETERMINATION OF NAPROXEN SODIUM AND ACETAMINOPHEN IN FIXED-DOSE COMBINATIONS FORMULATIONS BY FIRST-ORDER DERIVATIVE SPECTROSCOPY: APPLICATION TO DISSOLUTION STUDIES

Objective: To validate and apply a new and easy zero-crossing derivative method for the simultaneous determination of naproxen sodium and acetaminophen in fixed-dose combinations formulations.Methods: Measurement was achieved using the first-derivative (1D) signals at 243.42 nm for naproxen sodium and at 297.10 nm for acetaminophen. The method was validated according to International Conference on Harmonization (ICH) guidelines and was used to obtain the dissolution profiles (USP Apparatus 2, 75 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4) of five generic products and the reference product Febrax® (275/300 mg of naproxen sodium and acetaminophen, respectively). Dissolution data: percent of drug dissolved at 60 min, mean dissolution time (MDT) and dissolution efficiency (DE) were compared by a univariate one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparisons test. Differences were considered significant if *P<0.05. Additionally, data were adjusted to different kinetic models.Results: The method was linear (R2>0.99, *P<0.05) in the range of 10–50 µg/ml and 100–300 µg/ml for naproxen sodium and acetaminophen, respectively. The within-day and between-day precision and accuracy were within the acceptable criteria (relative standard deviation (RSD)<3% and 100±3%). Significant differences in MDT and DE values from all studies products were found (*P<0.05). All dissolution profiles were adjusted to Weibull's kinetics and significant differences in Td values were found (*P<0.05).Conclusion: The proposed derivative spectrophotometry method can be used for the simultaneous determination of naproxen sodium and acetaminophen in dissolution studies. The method is rapid, simple, accurate, and precise without the need of high cost investment.Â

Self perception of body attractiveness in two cultures: Mexican and Argentine

In order to describe the level of physical attractiveness that mexican and argentine consider having, we worked with an intentional non-probabilistic sample composed of 272 university students shared equally by nationality and gender from the cities of Toluca (Mexico) and Mendoza (Argentina). The instrument used was physical attractiveness assessment, which evaluates the attractiveness of the visible body parts from 0 to 100%. The research findings by nationality show that mexican people value more their body parts compared with argentinean. Sex differences indicate that mexican men tend to consider more attractive their body parts than mexican women. However, argentinean people show no difference in the number of body parts evaluated as attractive. In both nationalities, there is a tendency to put a higher value on body parts considered masculine by men and feminine by women. In general, it appears that the body is and will remain an important mean of expression and the value that it is given will establish the degree of security that people has to relate to their particular psychological, sociological and cultural context

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Towards a common vision of climate security in Guatamela

CGIAR’s Climate Resilience Initiative, also known as ClimBeR, is working to address these needs. On the 21st and 22nd of February, we ran in Guatemala City the first climate security workshop in Central America: Towards a common vision on the relationship between climate, conflict, and human security in Guatemala. The workshop was organized by the Alliance of Bioversity and CIAT along with the CGIAR’s Climate Resilience Initiative; the Fragility, Conflict, and Migration Initiative; the regional integrated initiative AgriLAC Resiliente; and the CGIAR FOCUS Climate Security and benefited from the participation of 45 individuals from 20 different organizations, including regional & local organizations, government institutions, UN agencies, and national universitie