Stability of high concentrated triple intrathecal therapy for pediatrics and mitigation strategies

Zanon, Davide; Selmin, Francesca; Centin, Giorgio; Maximova, Natalia; Casiraghi, Antonella; Minghetti, Paola

doi:10.1016/j.ejps.2021.106039

Cited by 1 publication

(1 citation statement)

References 22 publications

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“…Moreover, as further control, the compounding activity requires written standard operating procedures (SOPs), well-controlled equipment, and harmonised regulations [6]. Ultimately, the source of the active substance may require a specific evaluation, being not always available as the pure active ingredient used in industrial production, but rather necessitating the manipulation of a finished dosage form, such as tablets, capsules, or solutions [3,7]. Therefore, in order to ensure the required quality attributes and prevent the risk of compromising the treatment, the compounding activity in a pharmacy setting should be based on an experimental study aimed to verify the suitability [8,9] other than the stability of the preparation.…”

Section: Introductionmentioning

confidence: 99%

Critical Aspects in the Preparation of Extemporaneous Flecainide Acetate Oral Solution for Paediatrics

et al. 2021

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The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period.

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