Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use
- 1 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 2 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 3 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 4 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 5 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 6 Laboratorio de Farmacología, Instituto Nacional de Pediatría (INP)
- 7 Departamento de Anestesia y Quirófano, INP
- 8 Chocolates Turínò, S.A. de C.V.
Abstract
Aim: To develop an HPLC method to quantify midazolam in a new oral formulation for pediatric use. Methods: The stability of the new formulation was evaluated at different storage conditions and a preliminary assay of relative bioavailability was carried out in healthy volunteers. Results: The method of quantification was linear in the range of 5 to 60 μg·mL -1 . The midazolam amount in the formulation remained stable for 90 days at 4 and 40℃ (in the dark) while at 25℃ was stable only for 14 days (exposed to light). Discussion: The relative bioavailability assay suggests that our preparation of midazolam in white chocolate reaches plasma levels similar to those induced by the apple juice formulation. Conclusion: This new white chocolate formulation masks the unpleasing flavour and has a more attractive presentation to the paediatric patient, which may be useful for children sedation and to ease its management by health carers.
- M. C. Nahata, “Lack of Pediatric Drug Formulations,” Pediatrics, Vol. 104, 1999, pp. 607-609.
- M. C. Nahata and L. V. Allen Jr., “Extemporaneous Drug Formulations,” Clinical Therapeutics, Vol. 30, No. 11, 2008, pp. 2112-2119. doi:10.1016/j.clinthera.2008.11.020
- C. Flores-Pérez, J. Flores-Pérez, H. Juárez-Olguín and M. Barranco-Gardu?o, “Frequency of Drug Consumption and Lack of Pediatric Formulations,” Acta Pediatrica de México, Vol. 29, 2008, pp. 16-20.
- J. L. Blumer, “Clinical Pharmacology of Midazolam in Infants and Children,” Clinical Pharmacokinetics, Vol. 35, No. 1, 1998, pp. 37-47. doi:10.2165/00003088-199835010-00003
- S. L. Steedman, J. R. Koonce, J. E. Wynn and N. H. Brahen, “Stability of Mid-azolam Hydrochloride in a Flavored Dye Free Oral Solution,” American Journal of Hospital Pharmacy, Vol. 49, 1992, pp. 615-618.
- S. E. Walker, H. A. Grad, D. A. Haas and A. Mayer, “Stability of Parenteral Midazolam in an Oral Formulation,” Anesthesia Progress, Vol. 44, 1997, pp. 17-22.
- V. Bhatt-Mehta, C. E. Johnson, L. Kostoff and D. Rosen, “Stability of Midazolam Hydrochloride in Extemporaneously Prepared Flavored Gelatin,” American Journal of Hospital Pharmacy, Vol. 50, 1993, pp. 472-475.
- C. O. McMillan, I. A. Spahr-Schopfer, N. Sikich, E. Hartley and J. Lerman, “Pre-medication of Children with Oral Midazolam,” Canadian Journal of Anaesthesia, Vol. 39, No. 6, 1992, pp. 545-550. doi:10.1007/BF03008315
- Federal Register-67 FR 62171, White Chocolate, Establishment of a Standard of Identity, 2002. http://www.fda.gov/Food/LabelingNutrition/FoodLabelingGuidanceRegulatoryInformation/RegulationsFederalRe- gisterDocuments/ucm189430.htm
- Norma Oficial Mexicana NOM-073-SSA1-2005, Diario Oficial de la Federación, 2006.
- NORMA Oficial Mexicana NOM-177-SSA1-1998, Diario Oficial de la Federación, 1999.
- H. A. Argente and M. E. álvarez, “Semiología Médica. Fisiopatología, Semiotecnia y Propedéutica. Ense?anza Basada en el Paciente,” Panamericana, México, 2005.
- J. Jurica, M. Dostálek, J. Konecny, Z. Glatz, E. Hadasová and J. Tomandl, “HPLC Determination of Mida-zolam and Its Three Hydroxy Metabolites in Perfusion Medium and Plasma from Rats,” Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 852, No. 1-2, 2007, pp. 571-577. doi:10.1016/j.jchromb.2007.02.034