IN VITRO EQUIVALENCE STUDY OF GENERIC NAPROXEN SODIUM TABLETS USING THE USP PADDLE APPARATUS AND THE FLOW-THROUGH CELL METHOD

Objective: To perform an in vitro equivalence study of naproxen sodium from six immediate release oral dosage forms under the hydrodynamic environments generated by the flow-through cell method and the USP paddle apparatus.Methods: Dissolution method was properly validated according to standard criteria. Dissolution profiles of all formulations were carried out with an automated flow-through cell (laminar flow at 16 ml/min with 22.6 mm cells) and the USP Apparatus 2 (50 rpm). 0.1 M phosphate buffer pH 7.4 at 37.0±0.5 °C was used as the dissolution medium. Spectrophotometric determination of drug at 332 nm was carried out during 45 min. Dissolution profiles were compared with model-dependent and independent approaches.Results: Significant difference with model-independent parameters, mean dissolution time and dissolution efficiency, using both USP apparatuses, were found (*P<0.05). Best fitting of dissolution data was obtained using the sigmoidal model (R2>0.99). Only with the flow-through cell method linear regression between mean dissolution time and t63.2% values was significant (*P<0.05).Conclusion: The study reveals significant differences in dissolution rate and a great variability for all naproxen sodium tablets when the USP paddle apparatus is used. The alternative dissolution test with the flow-through cell method allows obtaining reliable data which facilitates in vitro equivalence respect the reference product dissolution behavior.Â

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

Objective: To develop and validate a new and easy zero-crossing derivative method for the simultaneous determination of ketoprofen and acetaminophen in fixed-dose combination formulations and to demonstrate its application in dissolution studies.Methods: Measurement was achieved using the first derivative signals at 243.2 nm for ketoprofen and at 260.5 nm for acetaminophen. The method was validated according to ICH guidelines. The proposed method was applied for the simultaneous quantification of both drugs in samples taken during the study of dissolution profiles (USP Apparatus 2, 75 rpm and 900 ml of 0.1 M phosphate buffer pH 7.4) of Bifebral® reference product (100/300 mg ketoprofen and acetaminophen, respectively). Samples were also analyzed by a previously validated HPLC-PDA method. Dissolution profiles were compared by similarity factor f2. Additionally values of: t50%, t85%, dissolution efficiency and mean dissolution time, obtained for ketoprofen and acetaminophen using UV and HPLC-PDA methods, were compared by Student's t-test.Results: The first derivative spectrophotometric method was linear in the range of 25–200 µg/ml for ketoprofen and 25–150 µg/ml for acetaminophen (R2>0.99, *P<0.05). The within-day and between-day precision and accuracy were within the acceptable criteria (RSD<3.4% and 100±3%). Similarity factor f2 was 85.85 and 88.49 for ketoprofen and acetaminophen, respectively. No significant differences between data obtained with UV and HPLC-PDA methods were found (*P>0.05).Conclusion: The proposed method can be used for the simultaneous determination of ketoprofen and acetaminophen, from fixed-dose combination formulations, in dissolution studies. The method is rapid, simple, accurate, and precise without the need of high-cost investment.Keywords: Ketoprofen, Acetaminophen, Derivative spectroscopy, Zero-crossing method, Dissolution studies.Â

IN VITRO EVALUATION OF NAPROXEN SODIUM AND ACETAMINOPHEN FROM FIXED-DOSE COMBINATION GENERIC DRUGS USING THE FLOW-THROUGH CELL METHOD

Objective: The aim of this study was the in vitro evaluation of naproxen sodium and acetaminophen from fixed-dose combination generic drugs based on the hydrodynamic environment generated by the flow-through cell method (USP Apparatus 4).Methods: Dissolution studies were carried out using a USP Apparatus 4 Sotax CE6 with 22.6 mm cells, laminar flow at 16 ml/min, and 0.1 M phosphate buffer pH 7.4 at 37.0±0.5 °C as dissolution medium. Both drugs were identified and quantified by a validated first-order derivative spectrophotometric method. Measurements were achieved at 243.26 and 297.0 nm for naproxen sodium and acetaminophen, respectively. Dissolution profiles of generic drugs were compared with similarity factor f2, t50%, t85%, t90% values as well as model-dependent and independent methods.Results: According to f2 values, dissolution profiles of all generic drugs were considered dissimilar to the dissolution profiles of the reference product (f2<50). Significant differences in t50%, t85%, t90%, mean dissolution time and dissolution efficiency values were found (*P<0.05). Dissolution data better adjusted to Makoid-Banakar and Weibull's kinetic models.Conclusion: The flow-through cell method was adequate for the in vitro evaluation of fixed-dose combination generic drugs containing naproxen sodium and acetaminophen. It should be necessary to evaluate the in vivo performance of fixed-dose generic formulations that contain naproxen sodium and acetaminophen in order to assure bioequivalence.Keywords: Naproxen sodium, Acetaminophen, Flow-through cell method, Fixed-dose combination generic drugs, First-order derivative spectrophotometry. 1.        Ruiz ME, Gregorini A, Talevi A, Volonté MG. Dissolution studies of generic medications: new evidence of deviations from the transitivity principle. Dissol Technol 2012;19:13−24.2.        Shokin IE, Ramenskaya GV, Vasulenko GF, Malalshenko EA. Assessment of the possibility of using comparative in vitro dissolution kinetics (biowaiver) instead of in vitro bioequivalence evaluation for establishing the inter-changeability of generic drugs. Pharm Chem J 2011;45:107−9.3.        Jayasheel BG. Regulatory requirements for marketing fixed dose combinations. Perspect Clin Res 2010;1:120−3.4.        Mitra A, Wu Y. Challenges and opportunities in achieving bioequivalence for fixed-dose combination products. AAPS J 2012;14:646−55.5.        Faasen F, Vromans H. Biowaivers for oral immediate-release products. Clin Pharmacokinet 2004;45:1117−26.6.        Kalantzi L, Reppas C, Dressman JB, Amidon GL, Junginger HE, Midha KK, et al. Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol). J Pharm Sci 2006;95:4−14.7.        Palma-Aguirre JA, Villalpando-Hernández J, Novoa-Heckel G, Oliva I, Cariño L, López-Bojórquez E, et al. Bioavailability of two oral tablet and two oral suspension formulations of naproxen sodium/paracetamol (acetaminophen): single dose, randomized, open-label, two-period crossover comparisons in healthy Mexican adult subjects. Clin Ther 2009;31:399−410.8.        Kasim NA, Whitehouse M, Ramachandran C, Bermejo M, Lennernäs H, Hussain AS, et al. Molecular properties of the WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm 2004;1:85–96.9.        United States Pharmacopeia and National Formulary USP 38-NF 33: The United States Pharmacopeial Convention, Inc. Rockville, MD; 2015.10.     US FDA. Dissolution methods. Available from URL: http://www.accessdata.fda.gov/scripts/cder/dissolution/. [Last accessed on 24 Sep 2015].11.     Medina JR, López-Tableros CA, Hernández-Altamirano G, Alarcón-Ãngeles G, Hurtado M, Domínguez-Ramírez AM. Simultaneous determination of naproxen sodium and acetaminophen in fixed-dose combinations formulations by first-order derivative spectroscopy: application to dissolution studies. Int J Pharm Pharm Sci 2015;7:183−8.12.     Chevalier E, Viana M, Artaud A, Chomette L, Haddouchi S, Devidts G, et al. Comparison of three dissolution apparatuses for testing calcium phosphate pellets used as ibuprofen delivery systems. AAPS PharmSciTech 2009:10:597−605.13.     Greco K, Bergman TL, Bogner R. Design and characterization of a laminar flow-through dissolution apparatus: comparison of hydrodynamic conditions to those of common dissolution techniques. Pharm Dev Technol 2011;16:75−87.14.     Shiko G, Gladden LF, Sederman AJ, Connolly PC, Butler JM. MRI studies of the hydrodynamics in a USP 4 dissolution testing cell. J Pharm Sci 2011;100:976−91.15.     Szymanska E, Winnicka K. Comparison of flow-through cell and paddle methods for testing vaginal tablets containing a poorly water-soluble drug. Trop J Pharm Res 2013;12:39–44.16.     Emara LH, Emam MF, Taha NF, El-Ashmawy AA, Mursi NM. In-vitro dissolution study of meloxicam immediate release products using flow-through cell (USP apparatus 4) under different operational conditions. Int J Pharm Pharm Sci 2014;6:254−60.17.     Jinno J, Kamada N, Miyake M, Yamada K, Mukai T, Odomi M, et al. In vitro-in vivo correlation for a wet-milled tablet of poorly water-soluble cilostazol. J Controlled Release 2008;130:29−37.18.     Jantratid E, De Maio V, Ronda E, Mattavelli V, Vertzoni M, Dressman JB. Application of bio-relevant dissolution tests to the prediction of in vivo performance of diclofenac sodium from an oral modified-release pellet dosage form. Eur J Pharm Sci 2009;37:434−41.19.     Hurtado M, Vargas Y, Domínguez-Ramírez AM, Cortés AR. Comparison of dissolution profiles for albendazole tablets using USP apparatus 2 and 4. Drug Dev Ind Pharm 2003;29:777-83.20.     Medina JR, Salazar DK, Hurtado M, Cortés AR, Domínguez-Ramírez AM. Comparative in vitro dissolution study of carbamazepine immediate-release products using the USP paddles method and the flow-through cell system. Saudi Pharm J 2014;22:141−7.21.     Relación de Medicamentos de Referencia. Comisión Federal para la Protección contra Riesgos Sanitarios. México. Available from: URL: http://www.cofepris.gob.mx/AS/Documents/ Registro Sanitario Medicamentos/Rel_med_de_ref_15-08-2013. pdf. [Last accessed on 21 Nov 2015].22.     ICH, Q2B Validation of Analytical Procedures: Methodology, International Conference on Harmonization; 1996. Available from: URL: http://www.fda.gov/downloads/drugs/ guidance-complianceregulatoryinformation/guidances/ucm073384.pdf. [Last accessed on 24 Oct 2015].23.     Singh I, Aboul-Enein HY. Advantages of USP Apparatus IV (flow-through cell apparatus) in dissolution studies. J Iran Chem Soc 2006;3:220–2.24.     Gao Z. In vitro dissolution testing with the flow-through method: a technical note. AAPS Pharm Sci Tech 2009;10:1401–5.25.     Qui S, Wang K, Li M. In vitro dissolution studies of immediate-release and extended release formulations using flow-through cell apparatus 4. Dissolution Technol 2014;21:6−15.26.     Yuksel N, Kanik AE, Baykara T. Comparison of dissolution profiles by ANOVA-based, model-dependent and independent methods. Int J Pharm 2000;209:57−67.27.     Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DD Solver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010;12:263−71.28.     Langenbucher F, Benz D, Kurth W, Moller H, Otz M. Standardized flow-cell method as an alternative to existing pharmacopoeial dissolution testing. Pharm Indian 1989; 51:1276−81.29.     Steffansen B, Brodin B, Und Nielsen C. editors. Molecular Biopharmaceutics. ULLA Pharmacy Series. Pharmaceutical Press; 2010.30.     Sunesen VH, Pedersen BL, Kristensen HG, Müller A. In vitro in vivo correlations for a poorly soluble drug, danazol, using the flow-through dissolution method with relevant dissolution media. Eur J Pharm Sci 2005;24:305−13.31.     Demirtürk E, Öner L. In vitro-in vivo correlations. FABAD J Pharm Sci 2003;28:215−24.32.     Anderson NH, Bauer M, Boussac N, Khan-Malek R, Munden P, Sardaro M. An evaluation of fit factors and dissolution efficiency for the comparison of in vitro dissolution profiles. J Pharm Biomed Anal 1998;17:811−22.33.     Anand O, Yu LX, Conner DP, Davit BM. Dissolution testing of generic drugs: and FDA perspective. AAPS J 2011;13:328−35

Sustainability and Impact of a Lung Health Outpatient Resource Center

BACKGROUND: According to the Worldwide Health Organization, worldwide, it is estimated hundreds of millions of people are affected by chronic respiratory diseases. COPD is a leading cause of death in the United States, and imposes an enormous financial burden on our nation\u27s health care system (COPD. NIH.GOV). COPD patients with severe exacerbations requiring emergency visits or hospitalizations per year are at higher risk for all- cause mortality (Soler-Cataluna JJ, et al. Thor-ax.200,60:925-931 ). A multidisciplinary Lung Health Outpatient Resource Center was established as a continuum of care to support our COPD population post discharge. Patients seen in the center showed successful outcomes, which have led to decreasing readmissions and improved cost savings. Therefore, the center expanded its services to include other chronic pulmonary diseases including pneumonia and pleurisy, asthma, bronchitis, and other respiratory infections. METHODS: The multidisciplinary team was headed by the Respiratory Department in con-junction with the Outpatient clinic and included; nurse practitioners (ARNP), respiratory therapist (RT), registered nurses (RN), social worker (SW), pulmonologist and pharmacy. The center incorporates weekly follow up visits during the acute phase post discharge where symptom management, individualized action plans, interpersonal psychosocial and emotional support is provided and created with the patient and family. Pharmacological and non-pharmacological interventions are utilized to optimize the individual\u27s treatment goal. RESULTS: The Lung Health Outpatient Resource Center was established in June 2017. Data was collected from June 2017 to March 2019. Total population referred was 304 patients. Patients seen in the center (150) had an 8% readmission rate, and those not seen (154) had a 12.9% readmission rate. The estimated average variable cost savings for patients seen was of $1,217,206.90 CONCLUSION: Through utilizing an outpatient resource center and adherence to plan of care, hospital readmission rates were decreased and variable cost savings improved. Sustainability by expanding our services to other chronic pulmonary diseases has been shown

Valorización de leche Gloria S.A.

Leche Gloria S.A. tiene 80 años como líder en el sector de leche industrializada. El objetivo principal del presente trabajo de investigación es estimar el valor intrínseco de la acción de la empresa a partir de las metodologías, conocimientos y herramientas aprendidas en la Maestría de Finanzas, incorporando el contexto de la pandemia por COVID-19. Leche Gloria S.A. está integrada verticalmente, siendo responsable del acopio, producción, envasado, venta y comercializacíón de lácteos, derivados lácteos y otros productos de consumo masivo. Se caracteriza por la diversificación de sus productos que están dirigidos a distintos segmentos de clientes, y por las inversiones que realiza para mejorar sus procesos productivos. Además, se identifica que tiene un alto poder de negociación con los proveedores, que le permite obtener ventaja competitiva basada en su liderazgo en costos. Del análisis financiero, se concluye que la empresa presenta saludables ratios de liquidez y apalancamiento, y que tiene mejores ratios de rentabilidad que sus comparables y, en el Perú, el consumo per cápita de leche es de 87 litros al año, siendo lo recomendado 120 litros al año según la Organización de las Naciones Unidas de la Alimentación y la Agricultura (FAO) (La República, 2020)

Modelización espacial de trips (insecta: thysanoptera) en el cultivo de aguacate (persea americana)

SE LOGRÓ ESTABLECER MEDIANTE MODELIZACIÓN ESPACIAL LA DISTRIBUCIÓN DE LAS POBLACIONES DE TRIPS EN AGUACATE EN EL ESTADO DE MÉXICO.México es el principal productor y exportador de aguacate en el mundo. Los trips son considerados una de las principales plagas de este cultivo, ya que se alimentan del fruto pequeño y forman crestas o protuberancias, las cuales al crecer el fruto son más visibles, y este pierde valor económico. Además de este daño, las heridas causadas por los trips son el principal causante para que entre la enfermedad denominada roña de fruto. Las alternativas de control de los trips han carecido de eficacia debido, entre otras causas, a que se desconoce su distribución espacial dentro de las huertas de aguacate. Este trabajo tuvo por objetivo determinar la distribución espacial de las poblaciones de trips en aguacate mediante el uso de técnicas de estadística espacial que condujeron a la generación de mapas por medio del “krigeado”. Los resultados demostraron que las poblaciones de trips presentan una distribución de tipo agregada, que fue corroborada por los mapas de densidad. Las infestaciones se distribuyeron en el 100 % de la superficie de las dos parcelas experimentales, lo cual resulta interesante para dirigir las medidas de control sobre áreas específicas de infestación. Se logró determinar estabilidad espacial y temporal a corto plazo de las poblaciones de trips

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

Sexual and Reproductive Health for Young Adults in Colombia: Teleconsultation Using Mobile Devices

Background: Sexual risk behaviors associated with poor information on sexuality have contributed to major public health problems in the area of sexual and reproductive health in teenagers and young adults in Colombia. Objective: To report our experience with the use of DoctorChat Mobile to provide sexual education and information among university students in Bogota, Colombia, and knowledge about the sexual risk factors detected among them. Methods: A mobile app that allows patients to ask about sexual and reproductive health issues was developed. Sexual and reproductive risk behaviors in a sample of young adults were measured before and after the use of the app through the validated survey Family Health International (FHI) Behavioral Surveillance Survey (BSS) for Use With Adults Between 15 and 49 Years. A nonprobabilistic convenience recruitment was undertaken through the study´s webpage. After completing the first survey, participants were allowed to download and use the app for a 6-month period (intervention), followed by completion of the same survey once again. For the inferential analysis, data was divided into 3 groups (dichotomous data, discrete quantitative data, and ordinal data) to compare the results of the questions between the first and the second survey. The study was carried out with a sample of university students between 18 and 29 years with access to mobile phones. Participation in the study was voluntary and anonymous. Results: A total of 257 subjects met the selection criteria. The preintervention survey was answered by 232 subjects, and 127 of them fully answered the postintervention survey. In total, 54.3% (69/127) of the subjects completed the survey but did not use the app, leaving an effective population of 58 subjects for analysis. Of these subjects, 53% (31/58) were women and 47% (27/58) were men. The mean age was 21 years, ranging between 18 and 29 years. The differences between the answers from both surveys were not statistically significant. The main sexual risk behaviors identified in the population were homosexual intercourse, nonuse of condoms, sexual intercourse with nonregular and commercial partners, the use of psychoactive substances, and lack of knowledge on symptoms of sexually transmitted diseases and HIV transmission. Conclusions: Although there were no differences between the pre- and postintervention results, the study revealed different risk behaviors among the participating subjects. These findings highlight the importance of promoting high-impact educational strategies on this matter and the importance of providing teenagers and young adults with easily accessible tools with reliable health information, regardless of their socioeconomic status