Feasibility study of an oral formulation of pyridoxine in the treatment of pharmacoresistant epilepsies

Introduction
Vitamin B6 is used in some vitamin-responsive epilepsies. In case of drug resistance, a treatment based on ketogenic diet (KD) is sometimes suggested. Current galenic forms are not suitable to pediatric use. Inorpha^® is the only aqueous-based ready-to-use vehicle suitable for KD, but pyridoxin stability into it is not documented. The bitter taste of pyridoxin needs a work on the formulation to improve observance. The goal of this work is to study the feasibility of a liquid form of pyridoxin with passable palatability.

Materials and methods
As pyridoxin is soluble in water, the finale concentration of the formulation as been set to 50 mg/mL in Inorpha^®. In order to mask the bitterness of pyridoxin, sucralose and aroma has been used. Further to the first formulation test, 8 formula has been taken on and palatability tests has been realized with pyridoxin formulation composed of : Only Inorpha^® (A) as a control, sucralose and Inorpha (D), orange flavor (B), raspberry flavor (F), cherry flavor (H), lemon flavor (I), sucralose and cherry flavor (C), sucralose and raspberry flavor (E), sucralose and lemon flavor (G). The assessed criteria, marked from 0 to 5 (0 = very bad, 5 = very good), were organoleptic features : taste, solubility, bitterness, sweet flavor detected, sour taste, smell and a ranking by preferences was also done. The results has been analized by ANOVA at α risk of 5% with XLSTAT^® sofware and compared by statistical pair by a Fisher and Newmann Keuls post-hoc test. The ranking has been realized by addition of ranks attributed to each formulation.

Results
The palatability tests resultats, done by 25 volunteers, showed significal differences for all criteria except solubility. C formulation showed the better results for all studied criteria (mean ± standard deviation) except solubility with a bitterness of 4,040 ± 0,935, a sour taste of 3,400 ± 1,291 and a global taste of 4,04 ± 1,207. C formulation was liked distinctly of other formulations according to post-hoc tests. The ranking confirms that the most appreciated formulation was the C formulation with a score of 51. The formulations including sucralose and cherry or raspberry flavor were more likes than control formulation A. G and D formulations have similar resultats of A formulation. Formulations including only flavor were less appreciated than the A one.

Discussion/Conclusion
The formulation including a sweetener (sucralose) and a flavor (cherry) enables efficient taste masking and suitable to pediatric population. An analysis method by HPLC-UV of this formulation has been made in order to assess its stability. If the formulation was stable, it would be dispensed as hospital formulation. Other vitamins liquid forms could be used in KD following that same pathway and would able the care of these types of patient.