Physicochemical stability study of 10 µg/mL Clonidine hydrochloride oral suspension in Syrspend^® SF PH4 for pediatric use

Clonidine hydrochloride is used in pediatrics for several indications including hypertension, attention-deficit/hyperactivity disorder (ADHD), opioid withdrawal syndrome, and as premedication. Although commercial formulations are available as injectable solutions and tablets, these dosage forms are not well suited for paediatric use. To address this need, our hospital produces an extemporaneously compounded oral suspension of clonidine hydrochloride at 10 µg/mL. The use of this oral suspension has increased substantially in our institution, with the number of dispensed bottles rising from 24 in 2022 to 169 in 2025.
The aims of this work were to develop and validate a stability-indicating High Performance Liquid Chromatography (HPLC) method and to assess the stability of this preparation. In the longer term, this work will support the transition from extemporaneous compounding to a standardized hospital-grade formulation, ensuring consistent quality, improved availability, and safer use for pediatric patients.

The HPLC method was developed using a Hypersil GOLD column (Thermo Scientific, 100 x 2.1 mm; 3µm) and a mobile phase composed of water at pH 3 and acetonitrile in gradient elution at a flow rate of 0.4 mL/min. Quantification was performed by DAD-type UV detection (from 190 to 400 nm) and analyzed at 210 nm using Chromeleon V7.2 software (Thermofisher, USA). Forced degradation studies were conducted under stressed conditions, including acid and alkaline hydrolysis, oxidative degradation, and thermal stress.
To assess physicochemical stability, three batches were prepared, packaged in type III amber glass bottles and stored between 2-8°C and at 25 +/-2°C with 60% +/- 5% relative humidity. The stability study was performed at D0, D1, D3, D7, D14, D21, D28, D45, D90 and D180. Visual appearance, clonidine concentration, pH and osmolality were assessed at each time point.

Degradation products were observed and well separated only under oxidative conditions. No degradation products were detected under other stress conditions.
The analytical method was validated according to ICH Q2(R2) guidelines, over three days with two operators using two different HPLC columns. The method showed good linearity from 0.6 to 1.4 µg/mL, precision, accuracy, specificity and repeatability. No matrix effects were observed.
Clonidine concentrations remained above 95% of the initial concentration throughout the study. No significant changes in pH, osmolality, or visual appearance were observed.

The developed HPLC method was successfully validated and demonstrated suitability as a stability-indicating assay. The oral suspension remained physicochemically stable for at least 180 days under both storage conditions, supporting its future implementation as a standardized hospital-grade formulation. To complete this work, a microbiological stability study needs to be performed.

See the poster