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TCH-011 Development of Pyridoxal-5-Phosphate Hard Capsules For Paediatric Use
  1. C Serrano,
  2. P Joret,
  3. V Siorat,
  4. P Vaconsin,
  5. T Abarou,
  6. T Storme
  1. Hopital Robert Debre (Ap-Hp)

Abstract

Background The active form of vitamin B6, called pyridoxal-5-phosphate (P5P), is an essential cofactor for several enzymes involved in various pathways of intermediary metabolism. PNPO is the rate-limiting enzyme in the synthesis of pyridoxal from vitamin B6 and a lack of activity causes dependency on an external source of pyridoxal. Epileptic seizure is the clinical outcome of P5P deficiency.

Purpose To provide a dosage form suitable for newborns and children. Capsules containing standardised P5P were compounded. Moreover, a fully soluble powder blend was formulated to fill the capsules and a method to determine the stability of the P5P content was developed.

Materials and Methods Dissolution assays were performed using oral syringes as nurses do. Time to complete dissolution and concentration were determined at each test. P5P content was determined by HPLC-UV (205 nm). The mobile phase consisted of phosphate buffer (0.05 M; pH 2.6) at a flow rate of 1 ml/min. The right active ingredient was tested by adding vitamin B6 to samples. Degradation by-products in stress conditions were also determined. The method was validated according to ICH recommendations.

Results Strengths were standardised at 10, 25, 50, 100 or 250 mg/capsule. The adopted blend is quickly solubilised in water and has a sweet taste. The HPLC readings were linear (r² = 0.9994) at the wavelength used, indicating good reproducibility and repeatability (SD = 0.46%). No matrix effect due to the diluent was observed.

Conclusions As P5P is a low toxicity compound, a test treatment with P5P is given to every newborn with idiopathic seizure before any treatment with standard antiepileptics. This method allows rapid routine assay of P5P. Stability testing of 3 compounded batches is ongoing.

No conflict of interest.

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