Hydrochlorothiazide oral suspension 2mg/mL: study of stability in SyrSpend® SF PH4 powder

SyrSpend® SF powder, suspending vehicle, seems well suited for pediatric use because of the absence of excipient with known effect as some conservatives. Thus, the absence of sorbitol provides a low osmolarity suspension compared to other vehicles. The objective of this study was to evaluate the stability of the Hydrochlorothiazide (HCT) in oral suspension, using SyrSpend® SF powder.

An HCT oral suspension at 2mg/mL has been prepared with SyrSpend® reconstituted in water then divided into 9 vials: 3 vials stored at room temperature (T°C) protected from light, 3 vials stored at room T°C without protection from light and 3 vials stored between 4 - 8 degrees C protected from light. For each sampling time (day D0, D2, D7, D14, D28 and D71), chemical stability: quantification of HCT by high performance liquid chromatography (HPLC-UV) according to a method already validated, and physical stability: pH, osmolality and aspect of the suspension have been checked.

Up to D28, the evolution of the mean concentrations (n=3) of HCT for each conservation mode has not varied more than 10% compared to D0. At D71, the suspensions are no longer stable (degradation >10%) with the appearance at HPLC-UV of peak of degradation products. The pH has varied from more than one unit (4.22 to 5.23) for vials “Room T°C protected from light” at D28. The viscosity didn’t allow performing the osmolality of a repeatable manner despite the decision to dilute 1/3. No precipitation or color change was observed from D0 to J71.

The results tend to show that the HCT oral suspension 2mg/mL stored during 28 days between 4 - 8 degrees C in vehicle suspension tested remains stable. SyrSpend® powder not containing preserving agent, it would be interesting to study the microbiological stability. Considering thixotropy and pseudoplasticity of SyrSpend® powder, a lack of agitation could explain the non repeatability of osmolality measures.