Preparation and Physico-Chemical Stability of Dexamethasone Oral Suspension

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Dexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5 mg/mL dexamethasone oral suspension.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-Sweet</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17 mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Dexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2 °C or at 21±3 °C).</jats:p></jats:sec>

Preparation and Physicochemical Stability of Liquid Oral Dosage Forms Free of Potentially Harmful Excipient Designed for Pediatric Patients

“…Regardless of the type of storage conditions, the proportion of the initial concentration of dexamethasone, hydrochlorothiazide, phenytoin, or spironolactone remaining was within the limit set by the U.S. Pharmacopeia [26], meaning that the oral suspensions of each drug compounded using Syrspend® SF PH4 Dry were stable up to 60 days both at room temperature or under refrigeration. This result is similar to or greater than the stability period reported by others [9,10,11,12,13,14,15]. The physicochemical stability of the four oral liquid dosage forms was investigated for a period of 60 days since the microbiological stability of suspensions compounded using Syrspend® SF PH4 Dry has been demonstrated by the manufacturer over the same period [30].…”

“…To enable the appropriate volume of administration (preferably ≤1 mL for a newborn), according to the dose required in their therapeutic uses [6,8,28], we chose to prepare oral liquid dosage forms at a target concentration of 5 mg/mL for spironolactone, dexamethasone, and phenytoin and 2 mg/mL for hydrochlorothiazide. According to the literature, other authors have reported similar concentrations for oral liquid compounded preparations of the same APIs [10,13,15]. Some authors have proposed oral liquid dosage forms with lower strengths due to different therapeutic uses [12,14] or higher strengths since they were used in older children [9,11].…”

“…Moreover, the compounded liquid formulations display low osmolality (<100 mOsm/kg) compared to several other formulations (around 1600 mOsm/kg) [9,10,12], ensuring safe oral administration in neonates. Indeed, high osmolality, greater than 450 mOsm/kg, may lead to necrotizing enterocolitis in neonates, especially in premature newborns [29].…”

“…However, in many countries, formulations suitable for oral administration of these APIs to children are not currently commercially available. According to the literature, several methods to compound oral liquid preparations containing these APIs have been described [9,10,11,12,13,14,15]. These methods have used suspending vehicles formulated using suspending agents (sodium carboxymethylcellulose, xanthan gum), dispersant/humectants (propylene glycol, dimethicone), sweetening agents (sodium saccharin, sucrose), preservatives (methylparaben, propylparaben, sodium benzoate), and water as a solvent.…”

Validation of a Rapid and Easy-to-Apply Method to Simultaneously Quantify Co-Loaded Dexamethasone and Melatonin PLGA Microspheres by HPLC-UV: Encapsulation Efficiency and In Vitro Release

“…The offered analytical method has been established using a high performance liquid chromatography (HPLC) technique coupled with ultraviolet (UV) detection and is revealed as fast and cost-effective in routine pharmaceutical analyses. Although evidence has been presented for the feasibility of DX and MEL quantification, several methods lacking simultaneous determination of the two mentioned compounds, or with longer retention times, have been described [28][29][30]. To the authors' knowledge, there is no reversed phase HPLC-UV validated method in the literature for the quantification of DX and MEL simultaneously with a short analysis time that involves a reduction in solvent consumption.…”