Development and sedative effect of a new formulation of midazolam in chocolate bars

The aim of this work was to assess the stability and sedative effect of midazolam in chocolate bars. The stability of 5 g chocolate bars containing 6 mg midazolam hydrochloride was evaluated at room temperature (25 ± 2 °C), at 4 and 40 °C, by HPLC. Drug plasma levels were measured and the sedative effect was confirmed in six healthy volunteers according to the Ramsay’s scale. Data regarding chocolate bar administration were compared to those from the apple juice solution. Pharmacokinetic data were processed using the WinNonLin 5.2 software. Midazolam in chocolate bars remained stable for 14 days at room temperature and exposed to light; for 90 days at 4 and 40 °C protected from light, and showed a longer shelf life, better flavour and appearance, inducing the same sedative effect as the apple juice preparation. Raspberry flavour masked midazolam unpleasing taste most favourably.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and sedative effect of a new formulation of midazolam in chocolate bars

The aim of this work was to assess the stability and sedative effect of midazolam in chocolate bars. The stability of 5 g chocolate bars containing 6 mg midazolam hydrochloride was evaluated at room temperature (25 ± 2 °C), at 4 and 40 °C, by HPLC. Drug plasma levels were measured and the sedative effect was confirmed in six healthy volunteers according to the Ramsay’s scale. Data regarding chocolate bar administration were compared to those from the apple juice solution. Pharmacokinetic data were processed using the WinNonLin 5.2 software. Midazolam in chocolate bars remained stable for 14 days at room temperature and exposed to light; for 90 days at 4 and 40 °C protected from light, and showed a longer shelf life, better flavour and appearance, inducing the same sedative effect as the apple juice preparation. Raspberry flavour masked midazolam unpleasing taste most favourably.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Physicochemical stability of a metformin solution from three commercial brands

Pharmacological management of insulin resistance and dyslipidaemias in children and adolescents is required to prevent the development of metabolic syndrome (MS) and type II diabetes mellitus (DM2). Material and method: we developed extemporaneous formulations from 500 mg-tablets from three generic brands, commercially available in Mexican drugstores: MedimartTM, Farmacias del AhorroTM and Primer NivelTM, dissolved in water sweetened with Splenda, which made them palatable and allowed customised dose adjustment. Solutions were stored at four environmental conditions: 25oC exposed to light, 25oC protected from light, 4oC and 40oC, and their physicochemical stability was assayed. The stability of the drug was determined by ultra performance liquid chromatography and ultraviolet detection (UPLC-UV) and by measuring the pH of the stock solution. The mobile phase consisted of (KH2PO4) 0.1 M, pH = 6.5, 4.6 mM sodium dodecyl sulphate (SDS) and acetonitrile (63:7:30) at 0.8 mL/min, column VARIAN Pursuit C8 150 × 3.9 mm tempered at 40oC, with detection at 236 nm. Results: Metformin from all trademarks was stable at all storage conditions for up to 30 days, retaining more than 90% of the initial amount of active drug, with a pH of 7.4 ± 0.3. Conclusion: Metformin extemporaneous formulations may be developed from either the innovator or generic brands, having the advantage of saving money and conserving the stability of its physicochemical properties. Keywords: Generic metformin, Innovator metformin, Extemporaneous formulation, Physicochemical stability, UPLC-UV

Citotoxicidad de los edulcorantes Splenda® y Svetia® en formulaciones extemporáneas pediátricas

Antecedentes: en nuestro laboratorio se ha empleado previamente sucralosa (Splenda®) para edulcorar formulaciones extemporáneas de metformina; sin embargo, hay publicaciones que sugieren una posible toxicidad del Splenda® en seres humanos. Objetivo: determinar el efecto citotóxico de la sucralosa para producir muerte celular en células humanas, en cultivo in vitro, a la misma concentración que se ha empleado en la formulación extemporánea. Materiales y métodos: las células se sembraron en placas de 96 pozos y se incubaron con sucralosa (Splenda®) por 60 minutos, stevia (Svetia®) o metformina. Se comparó la toxicidad celular determinada por absorbencia de formazán en lector de ELISA. Se analizaron las diferencias mediante ANOVA (p ≤ 0.05). Resultados: no se comprobó citotoxicidad de las preparaciones endulzadas con sucralosa o stevia en comparación con la metformina sola. Conclusión: tanto sucralosa como stevia pueden utilizarse como edulcorantes de formulaciones farmacológicas extemporáneas

Determination of blood dexmedetomidine in dried blood spots by LC-MS/MS to screen therapeutic levels in paediatric patients.

Dexmedetomidine is an imidazole derivative, with high affinity for α2 adrenergic receptors, used for sedation, analgesia and adjuvant anaesthesia. In this study, an analytical method for the quantification of dexmedetomidine in dried blood spots was developed, validated and applied. The drug was extracted from dried blood spot by liquid extraction; the separation was carried out by ultra high-resolution liquid chromatography in reverse phase coupled to tandem mass spectrometry method. An X Select cyano 5 μm HSS column (2.1 X 150 mm, Waters) and a mobile phase composed of 0.1% formic acid: acetonitrile [50:50 v/v], were used. The test was linear over the concentration range of 50 to 2000 pg/mL. The coefficients of variation for the intra and interday trials were less than 15%. The drug was stable under the conditions tested. The method was successfully applied for the quantification of 6 patients, aged 0 to 2 years, with classification ASA I, who underwent ambulatory surgeries, receiving a dose of 1 μg/Kg dexmedetomidine IV. The drug concentrations in the different sampling times were in the range of 76 to 868 pg/mL

Chromatograms for multiple reaction monitoring (MRM) of individual channels.

<p>The figure shows Ifosfamide and cyclophosphamide on 24-h samples. Selectivity to other drugs administered with ifosfamide: vincristine, ondansetron, etoposide, carboplatin and methotrexate.</p

Validation parameters of the analytical method by UPLC-MS/MS, to quantify ifosfamide in DBS at 30% HTC.

<p>SD: Standard Deviation. CV: Coefficient of Variation. N/R: Not required according to the guidelines. Theoretical amounts for QC1, QC2 and QC3 were 300, 4000 and 8000 ng/mL, respectively.</p><p>Validation parameters of the analytical method by UPLC-MS/MS, to quantify ifosfamide in DBS at 30% HTC.</p

Comparison between medians for blood ifosfamide levels obtained from DBS.

<p>The figure shows a comparison between medians for blood ifosfamide levels obtained from DBS after 12 hours (dark gray box) and 24 hours (Light gray box), p <0.0001.</p

Validation parameters of the analytical method for to quantify ifosfamide in DBS at 45% HTC.

<p>The intra-day variability with quality controls was performed in three consecutive days, data for days 1 to 3 are depicted as a, b and c, respectively. SD: Standard Deviation. CV: Coefficient Variation. N/R: Not required according to the guidelines. Amount claimed for QC1, QC2 and QC3 were 300, 4000 and 8000 ng/mL, respectively.</p><p>Validation parameters of the analytical method for to quantify ifosfamide in DBS at 45% HTC.</p