Solid Dosage Forms of Dexamethasone Sodium Phosphate Intended for Pediatric Use: Formulation and Stability Studies

Undesirable taste has always been a key issue for oral dosage forms. The aim of the present study was to co-formulate dexamethasone sodium phosphate (DSP), in common pediatric oral forms, using sweet preserves and/or different types of chocolate as excipients. An array of different kinds of chocolate were co-formulated with DSP and were further characterized by means of dynamic light scattering (DLS), x-ray diffraction (XRD), differential scanning calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. For the assay of active pharmaceutical ingredient (API), the chocolate samples were pre-treated by means of liquid extraction and analyzed using an high-performance liquid chromatographic (HPLC) method with a strong anion exchange column and a phosphate buffer (17 mM, pH = 3)/acetonitrile, 50:50 v/v as mobile phase. The developed chromatographic method was validated based on the International Conference on Harmonization (ICH) guidelines (%Mean Recovery = 99.4% and %Relative Standard Deviation, RSD = 0.43%). Furthermore, dissolution and in vitro digestion tests of chocolate formulations were evaluated. The DSP was found to be stable for at least 1 year in prepared preparations.

[1]  G. De Rosa,et al.  Patient Centric Pharmaceutical Drug Product Design—The Impact on Medication Adherence , 2020, Pharmaceutics.

[2]  Peng Li,et al.  Monodisperse molecularly imprinted microsphere cartridges coupled with HPLC for selective analysis of dexamethasone and hydrocortisone in cosmetics by using matrix solid-phase dispersion , 2019, Analytical Methods.

[3]  C. Markopoulou,et al.  Innovative Pediatric Formulations: Ibuprofen in Chocolate-Coated Honey Core , 2019, Journal of Pharmaceutical Innovation.

[4]  R. Strickley.  Pediatric Oral Formulations: An Updated Review of Commercially Available Pediatric Oral Formulations Since 2007. , 2019, Journal of pharmaceutical sciences.

[5]  Daicheng Liu,et al.  Detection and analysis of 17 steroid hormones by ultra-high-performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-MS) in different sex and maturity stages of Antarctic krill (Euphausia superba Dana) , 2019, PloS one.

[6]  A. Andrés,et al.  Lipids digestibility and polyphenols release under in vitro digestion of dark, milk and white chocolate , 2019, Journal of Functional Foods.

[7]  S. M. Sharkawi,et al.  Simultaneous Determination of Thalidomide and Dexamethasone in Rat Plasma by Validated HPLC and HPTLC With Pharmacokinetic Study. , 2018, Journal of chromatographic science.

[8]  A. Górska,et al.  A comparative study of thermal and textural properties of milk, white and dark chocolates , 2019, Thermochimica Acta.

[9]  M. Granados,et al.  Analysis of corticosteroids in samples of animal origin using QuEChERS and ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry , 2018, Analytical and Bioanalytical Chemistry.

[10]  Guoning Chen,et al.  Facile preparation of magnetic molecularly imprinted polymers for the selective extraction and determination of dexamethasone in skincare cosmetics using HPLC. , 2018, Journal of separation science.

[11]  Javier Suárez-González,et al.  Safe use of Dexamethasone in pediatrics: design and evaluation of a novel stable oral suspension , 2018 .

[12]  Yan Wang,et al.  Rapid determination of 18 glucocorticoids in serum using reusable on-line SPE polymeric monolithic column coupled with LC-quadrupole/orbitrap high-resolution mass spectrometer. , 2017, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[13]  Liying Huang,et al.  Optimization of dispersive liquid‐phase microextraction based on solidified floating organic drop combined with high‐performance liquid chromatography for the analysis of glucocorticoid residues in food , 2017, Journal of pharmaceutical and biomedical analysis.

[14]  Adam Rogers,et al.  Chocolate , 1995, SIGGRAPH Computer Animation Festival.

[15]  J. Cichero,et al.  In vitro digestion of infant formulations with hydrolysed and non-hydrolysed proteins from dairy and soybean. , 2016, Food & function.

[16]  H. Tikkanen,et al.  Dark chocolate and reduced snack consumption in mildly hypertensive adults: an intervention study , 2015, Nutrition Journal.

[17]  M. Corredig,et al.  A standardised static in vitro digestion method suitable for food - an international consensus. , 2014, Food & function.

[18]  P. García-García,et al.  Effects of selected amino acids and water-soluble vitamins on acrylamide formation in a ripe olive model system , 2014 .

[19]  J. Vieira,et al.  Cocoa particles for food emulsion stabilisation. , 2013, Food & function.

[20]  E. Begg,et al.  Determination of dexamethasone and dexamethasone sodium phosphate in human plasma and cochlear perilymph by liquid chromatography/tandem mass spectrometry. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[21]  Yan Zhang,et al.  Rapid simultaneous determination of dexamethasone and betamethasone in milk by liquid chromatography tandem mass spectrometry with isotope dilution. , 2010, Journal of chromatography. A.

[22]  J. Breitkreutz,et al.  Challenges of developing palatable oral paediatric formulations. , 2009, International journal of pharmaceutics.

[23]  A. Kende,et al.  Analysis of dexamethasone and prednisolone residues in bovine milk using matrix solid phase dispersion-liquid chromatography with ultraviolet detection , 2008 .

[24]  S. Culine,et al.  Simultaneous determination of dexamethasone and 6 beta-hydroxydexamethasone in urine using solid-phase extraction and liquid chromatography: applications to in vivo measurement of cytochrome P450 3A4 activity. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[25]  P. Haddad,et al.  Ion Chromatography , 2004, Analytical and bioanalytical chemistry.

[26]  Ghulam A. Shabir,et al.  Step-by-step analytical methods validation and protocol in the quality system compliance industry , 2004 .

[27]  H. Goicoechea,et al.  Determination of dexamethasone and two excipients (creatinine and propylparaben) in injections by using UV-spectroscopy and multivariate calibrations. , 2001, International journal of pharmaceutics.