AJAC  Vol.3 No.8 , August 2012
Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use
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.
Cite this paper: C. Pérez, J. Pacheco, J. Pérez, H. Olguín, B. Mendiola, R. Álvarez, J. Zamora and Á. Guerra, "Development and Validation of a Method to Quantify Midazolam in a New Oral Formulation for Pediatric Use," American Journal of Analytical Chemistry, Vol. 3 No. 8, 2012, pp. 552-558. doi: 10.4236/ajac.2012.38073.

[1]   M. C. Nahata, “Lack of Pediatric Drug Formulations,” Pediatrics, Vol. 104, 1999, pp. 607-609.

[2]   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

[3]   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.

[4]   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

[5]   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.

[6]   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.

[7]   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.

[8]   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

[9]   Federal Register-67 FR 62171, White Chocolate, Establishment of a Standard of Identity, 2002. gisterDocuments/ucm189430.htm

[10]   Norma Oficial Mexicana NOM-073-SSA1-2005, Diario Oficial de la Federación, 2006.

[11]   NORMA Oficial Mexicana NOM-177-SSA1-1998, Diario Oficial de la Federación, 1999.

[12]   H. A. Argente and M. E. álvarez, “Semiología Médica. Fisiopatología, Semiotecnia y Propedéutica. Ense?anza Basada en el Paciente,” Panamericana, México, 2005.

[13]   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

[14]   H. Sohi, Y. Sultana and Y. Khar, “Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches,” Drug Development and Industrial Pharmacy, Vol. 30, 2004, pp. 429-448. doi:10.1081/DDC-120037477

[15]   S. A. Ibrahim, T. H. El-Faham, S. S. Tous and E. M. Mostafa, “Formulation, Release Characteristics and Evaluation of Ibuprofen Suppositories,” International Journal of Pharmaceutics, Vol. 61, No. 1-2, 1990, pp. 1-7. doi:10.1016/0378-5173(90)90037-5

[16]   H. Suzuki, H. Onishi, Y. Takahashi, M. Iwata and Y. Machida, “Development of Oral Acetaminophen Chewable Tablets with Inhibited Bitter Taste,” International Journal of Pharmaceutics, Vol. 251, No. 1-2, 2003, pp. 123-132. doi:10.1016/S0378-5173(02)00595-1

[17]   E. H. Kim and H. K. Choi, “Preparation of Various Solid-Lipid Beads for Drug Delivery of Enrofloxacin,” Drug Delivery, Vol. 11, 2004, pp. 365-370. doi:10.1080/10717540490265414

[18]   A. A. Adeagboo and G. Alebiowu, “Evaluation of Cocoa Butter as Potential Lubricant for Coprocessing in Pharmaceutical Tablets,” Pharmaceutical Development and Technology, Vol. 13, 2008, pp. 197-204. doi:10.1080/10837450801949400

[19]   M. D. Reed, A. Rodarte, J. L. Blumer, K. C. Khoo, B. Akbari and S. Pou, “The Single-Dose Pharmacokinetics of Midazolam and Its Primary Metabolite in Pediatric Patients after Oral and Intravenous Admin-istration,” Clinical Pharmacolology, Vol. 41, 2001, pp. 1359-1369.

[20]   J. Martens-Lobenhoffer, S. Eisenhardt, U. Tr?ger, W. R?se and F. P. Meyer “The Effect of Anxiety and Personality on the Pharmacokinetics of Oral Midazolam,” Anesthesia and Analgesia, Vol. 92, No. 3, 2001, pp. 621-624. doi:10.1213/00000539-200103000-00012

[21]   R. Schwagmeier, S. Alincic and H. W. Striebel, “Midazolam Pharmacokinetics Following Intravenous and Buccal Administration,” Britain Journal of Clinical Pharmacology, Vol. 46, No. 3, 1998, pp. 203-206. doi:10.1046/j.1365-2125.1998.00781.x