Diseño y caracterización del sistema de administración flotante de fármacos de domperidona-famotidina combinatoria. Estudios in vitro e in vivo

Introducción: Los inconvenientes de la administración oral pueden controlarse o minimizarse mediante formulaciones gastro-retentivas que permanecen flotantes dentro del estómago durante un tiempo prolongado al proporcionar una retención gástrica prolongada y liberan el fármaco de una manera excesivamente prolongada mejorando así la biodisponibilidad. La investigación actual fue desarrollar y optimizar las tabletas flotantes de domperidona y famotidina con liberación prolongada mediante el enfoque Calidad por diseño. Método: Basado en QTPP (Perfil de producto objetivo de calidad), se identificaron CQA (Atributos críticos de calidad). El análisis de riesgos mediante la evaluación de los parámetros de formulación y proceso mostró que la optimización de los niveles de polímeros podría reducir el alto riesgo para lograr el perfil objetivo. Se seleccionó un diseño experimental de 2 factores de nivel 3 con puntos medios para el análisis estadístico y la optimización. Resultados: HPMC K100, Carbopol 934P tuvo un efecto positivo y la etilcelulosa tuvo un efecto negativo sobre las respuestas seleccionadas. La cinética de liberación del fármaco siguió a la liberación de primer orden con difusión de Higuchi y difusión de Fickian. Se seleccionó y evaluó una fórmula optimizada que satisfacía todos los parámetros requeridos. Los valores de respuesta previstos estaban en estrecha concordancia con los valores de respuesta experimental. Las imágenes de rayos X abdominales después de la administración oral de las tabletas en el estómago sano del conejo confirmaron el comportamiento de flotación prolongado con un tiempo de retraso más corto. Losin vivo estudios farmacocinéticosen conejos revelaron que la formulación optimizada exhibía una liberación prolongada del fármaco con una mayor Cmax, tmax, AUCo-t y t1 / 2 del producto Conclusiones: Se concluyó que la aplicación de Quality by Design en la formulación y optimización redujo el número de ensayos para producir una fórmula rentable.Introduction: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and releasethe drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. Method: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes)wereidentified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23 factor experimental design with midpoints was selected for statistical analysis and optimization. Results: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit’s stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2of an optimized product when compared to the marketed product. Conclusions: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula

PREPARATION AND EVALUATION OF QUETIAPINE FUMARATE MICROEMULSIONS: A NOVEL DELIVERY SYSTEM

Objective: In the present study, the main objective is to improve solubility and bioavailability of Quetiapine fumarate by formulation into micro emulsion. Method: The Quetiapine fumarate micro emulsion was formulated by using mixture of Isopropyl myristate and oleic acid as oil phase, Tween-80 as surfactant, Isopropyl alcohol and Ethanol mixture as co-surfactant by phase titration method. The prepared formulations were evaluated for Limpidity (% transmittance), droplet size, Zeta potential, Electrical conductivity, Rheology, pH, percentage of drug (assay), emulsifying time, in vitro drug diffusion studies and ex vivo permeation studies. Results and conclusion: The Optimized micro emulsion (Micro emulsion 11) formulation containing Quetiapine fumarate (25mg), Surfactant mixture (50%w/w), Oil (12%w/w) and distilled water (38%w/w) has a droplet size of 26.70 nm with a zeta potential of -5.62 millivolts. The micro emulsion was characterized and compared with the pure drug suspension. Microemulsion showed 31.25 fold increased solubility than that of pure drug suspension. In vitro drug release and ex vivo permeation study results were comparable and correlative. The Microemulsion 11 formulation showed 1.4763 times more drug release than that of pure drug suspension. The formulation was found to be stable for three months. Keywords: Microemulsion, Phase titration method, Quetiapine Fumarate,  Emulsifying time

VALIDATED STABILITY-INDICATING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD FOR THE ESTIMATION OF TORSEMIDE

Objective: This assessment depicts the strength of exhibiting reverse-phase high performance liquid chromatography (RP-HPLC) method for the estimation of torsemide in pharmaceutical estimation structures. Methods: In the present work, total protein-HPLC technique has been produced for the estimation of torsemide active pharmaceutical ingredient (API). Constrained degradation HPLC strategy was created with versatile mobile phase of methanol:water in the proportion of 90:10 v/v. The stream pace of 1 ml/min was utilized on Inertsil ODS 3V segment (250 mm×4.6 mm, 5 μm molecule size). Results: The retention time of torsemide was seen at 8.267 min, method was validated for all validation parameters as per the International Council for Harmonization guidelines. The linearity range was 10–60 μg/ml, correlation coefficient was 0.9993, and percentage relative standard deviation in the precision studies was <2%, with percentage recovery 100.56–101.03 (within acceptable range of 98–102%). The assay result was found to be 100.88% (i.e., within 95–105%), passes the specifications for robustness parameters. Limit of detection of torsemide was found to be 0.0162 μg/ml and limit of quantitation of torsemide was found to be 0.0534 μg/ml. Conclusion: The medication was exceptionally delicate to antacid pursued by at risk to corrosive, photolytic, warm, and oxidative conditions. The created and approved method showing HPLC technique is observed to be direct, exact, precise, explicit, and powerful. Henceforth, the technique can be utilized routinely for the estimation of torsemide API

PRELIMINARY PHYTOCHEMICAL AND STANDARDIZATION PARAMETERS OF IPOMOEA QUAMOCLIT LINN WHOLE PLANT-AN ETHNOMEDICINALLY IMPORTANT PLANT

Objective: Preliminary phytochemical studies and proximate analysis of Ipomoea quamoclit Linn whole plant. Methods: The whole plant was collected, shade dried and made into powder. The powdered plant material was studied for its proximate values which include ash values, extractive values, fluorescence analysis and moisture content by standard methods. The powdered plant material was subjected to successive solvent extraction by maceration using petroleum ether, chloroform, ethyl acetate, methanol, water and hydroalcoholic mixture as solvents. All the extracts were subjected to a preliminary phytochemical screening in which chemical tests were carried out for the detection of various phytoconstituents. Results: Proximate analysis revealed that the dry plant powder has 9.68% total ash, 3.57% acid insoluble ash, 2.95% water soluble ash, 3.49% sulphated ash, 12.92% alcohol soluble extractive value, 9.45% water soluble extractive values, 5.41% ether soluble extractive value and 5.25% moisture content. The whole plant powder found to possess phytoconstituents like alkaloids, carbohydrates, saponins, phenolic compounds, tannins, phytosterols, amino acids, proteins and flavonoids. Fluorescence analysis revealed the behavior of the plant powder when treated with different chemical reagents and observation under UV light at 365 nm. Conclusion: The present study reveals the preliminary phytochemical and proximate analysis of Ipomoea quamoclit whole plant

Will adoption of the 2010 WHO ART guidelines for HIV-infected TB patients increase the demand for ART services in India?

BACKGROUND: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIV-infected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/mm(3) or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients. METHODS: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records. RESULTS: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen. CONCLUSION: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIV-infected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme