3PC-012 Sodium pentobarbital rectal preparations: optimisation of a manufacturing process, and development of formulation

<h3>Background and Importance</h3> Pentobarbital (PTB) is a barbiturate used for paediatric sedation, without existing marketed specialties. This requires the use of hospital preparations. In our pharmaceutical department, PTB suppositories are produced. Between 2018 and 2023, batches revealed significant non-compliance issues, particularly with uniformity of content. To improve patient safety and efficacy, optimising paediatric sedation was necessary by improving the suppository manufacturing process and the development of a more stable alternative - a rectal solution of PTB. <h3>Aim and Objectives</h3> The aim of this study is to optimise paediatrics sedation by developing a new formulation (pentobarbital rectal solution) and determining its stability. <h3>Material and Methods</h3> An intra-rectal PTB solution in a sterile water-based formulation was prepared. The protocol included developing and validating a stability-indicating High-Performance Liquid Chromatography (HPLC) method to quantify pentobarbital, detect degradation products, and conduct a stability study. The HPLC method, developed using an XSelect column and a mobile phase composed of water (pH 3) and acetonitrile (65:35 v/v) in isocratic elution (flow rate 0.4 mL/min). Quantification was performed using UV detection analysed at 210 nm. Forced degradation tests under acidic, alkaline, oxidative, and thermal stress conditions were conducted. To assess physical-chemical stability, three batches were prepared, packaged in amber glass vials and syringes (two pieces) at 2–8°C and 25°C/60% relative humidity. Visual appearance, PTB concentration, pH and osmolality were evaluated throughout the study period (183 days). <h3>Results</h3> Degradation products were observed. Validation of the analytical method was carried out in accordance with ICH Q2 guidelines over 3 days, by two different operators. The validated method showed good repeatability, resolution, specificity, precision, accuracy, and linearity. The last day (Day 183) PTB concentration remained above 95% of the initial concentration for all batches. pH and osmolality and remained stable. An impurity appeared in D59 coeluted at room temperature (no appearance at 2–8°C) representing 0,8% (relative-area). <h3>Conclusion and Relevance</h3> Pentobarbital rectal solution can be produced and stored for 183 days at 2–8°C in vials and syringes, two pieces. The formation of coeluted impurities suggests that storage at room temperature is not recommended. Syringe packaging enables standard doses to be produced, limiting the risk of error and simplifying the administration process. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest