Pyridoxal phosphate mucoadhesive film: development and stability of an innovative formulation

Background
Pyridoxal phosphate (PLP) is increasingly used as first-line therapy for vitamin B6-dependent epilepsies, rare hereditary diseases requiring lifelong treatment from the neonatal period. Despite its clinical importance, no commercially available PLP dosage form suitable for pediatric use is currently available in our country. Hospital pharmacies must therefore develop preparations allowing individualized dosing. In this context, the development of a PLP mucoadhesive film was motivated by the potential pharmacokinetic benefits associated with oral mucosal absorption, as well as improved acceptability and adherence in the pediatric population. The aim of this work was to develop an innovative PLP mucoadhesive film and to establish a stability-indicating analytical method for its quality control.

Materials and Methods
Mucoadhesive films were prepared using the Novafilm™ excipient base (Medisca). Formulation parameters including PLP solubilization pH, drug loading and drying conditions were optimized. PLP quantification was performed using a validated ion-pair High Performance Liquid Chromatography – Photodiode array (HPLC–PDA) method. Chromatographic analysis was conducted on a reversed-phase C18 column (2.6 µm, 2.1 × 100 mm) under isocratic conditions, using a mobile phase consisting of 20 mM phosphate buffer (pH 6.8, 5 mM tetrabutylammonium sulfate) and acetonitrile (90:10, v/v). The method was developed according to ICH Q2(R2) guidelines, including assessments of specificity, accuracy, precision, matrix effects, and stability-indicating capability. Forced degradation studies were conducted under acidic, alkaline, oxidative, and photolytic conditions.

Results
Formulation optimization identified pH 7 as necessary to ensure complete PLP solubilization and prevent sedimentation by reaching saturation point during film manufacturing. Drying at 50°C under convection conditions minimized bubble formation and ensured acceptable film quality. The analytical method demonstrated satisfactory accuracy and precision and was not affected by matrix effects. Optimal detection was achieved at 388 nm. Forced degradation studies confirmed the stability-indicating capability of the method, allowing discrimination between PLP and degradation products.

Discussion/Conclusion
An original PLP mucoadhesive film suitable for pediatric hospital preparation was successfully developed, together with a validated stability-indicating analytical method. Ongoing stability studies will determine its suitability for routine hospital use. To complete the characterization of the formulation, future studies will assess dissolution performance and microbial preservation during storage. This work highlights the potential of mucoadhesive films as an innovative and simple dosage form for individualized pediatric formulations in hospital pharmacy.