Stability of Pentobarbital Hydrogel for Rectal Administration in Pediatric Procedural Sedation

Abstract

Purpose: Pentobarbital is a sedative agent to limit children motion during computed tomography or magnetic resonance imaging (MRI) and ensures the successful completion of the imaging procedure. However, data on rectal drug formulation and its stability in practice are not available. The aim of this study was to formulate and evaluate the stability of a ready-to-use rectal pentobarbital gel. Methods: The formulation consisted of a hydrated gel containing 25 mg/mL of pentobarbital sodium, packaged in 10-mL amber glass bottles and stored at either 22°C to 25°C or 2°C to 8°C. At each predetermined time point, samples were taken for visual inspection, pH measurement, and analysis by a validated stability-indicating high-performance liquid chromatography (HPLC) method. The viscosity parameters of the hydrogel formulation were assessed. Results: The freshly prepared rectal formulations appeared clear, colorless, and particular-free with pH readings of 9.75 to 9.83. Over the 90 days of the study period, there was no significant change in appearance or pH values for all stability samples. The HPLC results confirmed the chemical stability when stored at 2°C to 8°C or at 22°C to 25°C. Conclusion: Pentobarbital hydrogel 25 mg/mL are stable chemically at least 90 days and can be administered to children for an effective and fast sedation.

Development and Stability of a New Formulation of Pentobarbital Suppositories for Paediatric Procedural Sedation

“…The quality of the examination is related to a rapid onset, a moderate duration of action, and a minimisation of adverse effects [ 3 ]. For this reason, rectal solutions and hydrogels were developed to shortcut the lag time due to suppository dissolution [ 16 ], but suppositories have the advantage of being easy to handle and do not need a device to be administered. Although other formulations containing pentobarbital have been described in the literature, all of them contain at least one ingredient that is not recommended for paediatric patients.…”

“…The most recent rectal form study published was about a rectal hydrogel. The authors reported less than a 5% loss of pentobarbital after 90 days at 2 to 8 °C and 22 to 25 °C and did not mention the detection of any breakdown product [ 16 ].…”

“…Because pentobarbital is not marketed in any dosage form allowing a rectal administration, formulations of pentobarbital (and more specifically of pentobarbital sodium, as the salt form is readily available in pharmaceutical grade), such as those made by hospital pharmacists, are needed. Belo et al [ 16 ] recently developed a hydrogel formulation for rectal administration containing pentobarbital sodium at a concentration of 25 mg/mL. However, this formulation presented some disadvantages, such as containing sodium benzoate, which is an excipient with a known effect, especially on hormone levels and on inflammation, and can also have an irritating action on the gastric mucosa [ 17 ].…”