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3PC-006 Stability study of clobazam liquid oral forms for paediatric patients
  1. AL Leroy, L Régnier,
  2. N Le Potier Cornen,
  3. G Jouan,
  4. B Madigand,
  5. PN Boivin,
  6. MA Lester
  1. CHU Rennes, Pharmacie – Hôpital Sud, Rennes, France


Background and Importance Clobazam is a benzodiazepine used as an anti-epileptic drug for paediatric patients.

In our hospital, we faced several supply difficulties and even stock-outs of the oral suspension speciality for paediatric use. This treatment cannot be interrupted during a supply disruption and it is not possible to stop treatment initiation for this indication. As paediatric doses are weight-adjusted, the development of a liquid formulation was necessary to handle this supply issue.

Aim and Objectives The study aimed was to determine the stability of Clobazam drinkable forms in two different commercial compounding excipients.

Material and Methods A stability-indicating High Performance Liquid Chromatography method, with UV detection, was developed. Forced degradation of clobazam was studied under several conditions (acid and alkaline hydrolysis, oxidative, thermal stress).

Two formulations of clobazam at 2 mg/mL were produced: with Inorpha® and with Syrspend® SF PH4 liquid.

To assess physical-chemical stability, three batches of each formulation were prepared and packaged in amber glass vials, stored at 25°C ± 2°C with relative humidity at 60% ± 5%.

Visual appearance, clobazam concentration, pH and osmolality were evaluated throughout the study period (84 days).

Results The chromatographic method allowed good separation of clobazam and the degradation products. Its validation was performed in accordance with ICH Q2 guidelines over three days, by two different operators. The method showed good injection repeatability, specificity, precision, accuracy, linearity and no matrix effect from excipients.

At day 84, the clobazam concentration of both formulations remained above 95% of the initial concentration (101.4% in Inorpha® and 99.6% in Syrspend®).

PH (4.8 at D0, 4.7 at D84 in Inorpha® and 4.2 at D0, 4.1 at D84 in Syrspend®) and osmolality (169 mosmol/kg at D0, 170 mosmol/kg at D84 in Inorpha® and 52 mosmol/kg at D0, 53 mosmol/kg at D84 in Syrspend®) also remained stable in both batches.

Visual appearance remained unchanged A sedimentation with Inorpha® was observed, which explains interdays variability.

Conclusion and Relevance A liquid form of clobazam can therefore be produced in either Inorpha® or Syrspend® SF PH4 and stored for 84 days at 25°C, protected from light in case of supply shortage. The formulation with Syrspend® seems to guarantee a better homogeneity due to viscosity.

Conflict of Interest No conflict of interest.

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