Stability of extemporaneous sulfadiazine oral suspensions from commercially available tablets for treatment of congenital toxoplasmosis

Abstract

Objectives To determine the physicochemical and microbiological stability of sulfadiazine suspensions (100 mg/mL) in simple syrup (A) and sorbitol (B) formulations prepared from commercially available tablets. Methods An ultra‐performance liquid chromatographic assay was developed and validated to determine the chemical stability of sulfadiazine. Three samples were prepared and stored at 5 and 25 °C and assayed at 0, 7, 14 and 30 days. Physical parameters (appearance, pH, particle size and viscosity) were also monitored. Microbiological examination was performed through the suitable counting method. Results The formulations presented a sulfadiazine concentration of around 95% at the beginning at both temperatures. There was some variation in pH, viscosity and particle size distribution over time. The samples met the pharmacopoeia criteria of microbiological quality over 30 days, but only sulfadiazine formulated in syrup stored at 25 °C was suitable for use after one week. Conclusion The sulfadiazine suspension in simple syrup was chosen as the most suitable formulation because it demonstrated stability for 14 days at room temperature, providing an alternative liquid dosage form of sulfadiazine for congenital toxoplasmosis treatment.

Stability of sulfadiazine sugar-free oral suspensions for the treatment of congenital toxoplasmosis

“…The preparations were produced at a concentration of 100 mg/mL (Costa et al, 2020;Ferreira et al, 2016) to achieve the therapeutic dosage with the smallest volume of the formulation, considering the dosage for the treatment of congenital toxoplasmosis is 100 mg/ kg/day divided into two administrations. Additionally, formulations with smaller volumes are usually better tolerated by children (Khan et al, 2022;Nakama et al, 2019;Reis et al, 2021).…”

“…To opt i m i ze t he prev iou sly developed chromatographic technique (Costa et al, 2020), a UPLC method was validated using a gradient elution to provide separation of SDZ and methylparaben. With the optimization, the SDZ peak was detected at 2.6 minutes, and methylparaben was detectable at 7.3 minutes only when concentrated solutions were analyzed (data not shown), which is due to the difference in concentration between SDZ and methylparaben (Supplementary information; Figure S1).…”

“…Before the microbiological evaluation, a validation step was performed to ensure that the antimicrobial action of SDZ and methylparaben would not interfere in the analysis. For this, the formulations were diluted in phosphate buffer pH 7.2 containing polysorbate 80 (3% v/v) (ANVISA, 2019a) and PABA (1:1 ratio of SDZ:PABA) (Costa et al, 2020), both well-known inactivating agents of the preservative and SDZ, respectively. The neutralizing action and absence of toxicity of both inactivating agents for microorganisms were evaluated by measuring their recovery using suspensions of test strains containing around 100 CFU of Pseudomonas aeruginosa (ATCC 9027), Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 8739) and Candida albicans (ATCC 10231).…”

“…In such context, the literature reports studies that evaluated the stability of SDZ in suspension prepared by crushing tablets or drug powder and dispersed in water for injection (Pathmanathan et al, 2004), commercial vehicle (Ferreira et al, 2016) and simple syrup and sorbitol (Costa et al, 2020). However, these formulations present some components that can limit their use by some pediatric patients.…”

Insights into folic acid mixtures compounded with commercially available vitamin syrups

“…Drugs are compounded as suspensions in order to meet the needs of special patients such as pediatric, geriatric and tube-fed patients (Cutaia et al, 2018;Allen, 2019). Studies have reported variations in pH, viscosity, particle size distribution, API content and microbial contamination of extemporaneous preparations, and suggested that such preparations were suitable for use only for a specified period of time, thus leading to the introduction of beyond-use-dates (BUD), after which the preparation cannot be consumed (Alfred-Ugbenbo et al, 2017;Silva et al, 2020;Soares Rodrigues Costa et al, 2020). However, the bioavailability and palatability of such preparations can still not be proven, even though they have been found to be physically, chemically or microbiologically stable, until they are supported by evidenced based data (Belayneh and Tessema, 2021).…”