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

Area of Science:

• Pharmaceutical Sciences
• Pediatric Pharmacology

Background:

• Pentobarbital is crucial for limiting motion in pediatric procedural sedations (PPSs).
• Rectal administration is preferred for pediatric patients, but pentobarbital suppositories are not commercially available, necessitating compounding.
• This study addresses the need for stable, effective pentobarbital suppository formulations for pediatric use.

Purpose of the Study:

• To develop and characterize two pentobarbital sodium suppository formulations for pediatric procedural sedations.
• To evaluate the physical properties and stability of the developed formulations.
• To identify the optimal formulation for potential clinical application.

Main Methods:

• Two pentobarbital sodium suppository formulations (F1: Witepsol W25 alone; F2: Witepsol W25 with oleic acid) were prepared in varying dosages (30-60 mg).
• Formulations underwent European Pharmacopoeia testing: uniformity of dosage, softening time, resistance to rupture, and disintegration time.
• Stability was assessed over 41 weeks at 5 ± 3 °C using stability-indicating liquid chromatography to quantify pentobarbital sodium and breakdown products.

Main Results:

• Both formulations met uniformity of dosage requirements.
• Formulation F2 exhibited significantly faster disintegration (63% faster) than F1.
• Formulation F1 remained stable after 41 weeks, while F2 showed signs of degradation, indicating a stability of approximately 28 weeks.

Conclusions:

• Formulation F1, utilizing Witepsol W25 alone, offers superior long-term stability for pentobarbital suppositories.
• Formulation F2, containing oleic acid, disintegrates faster but has a shorter shelf-life.
• Further clinical studies are required to confirm the safety and efficacy of both formulations for pediatric procedural sedations.