Novel orally Disintegrating Edible Films with Ursodeoxycholic Acid for the Treatment of Hepatobiliary Diseases in Pediatric Patients.

PURPOSE: Ursodeoxycholic acid (UDCA) has low toxicity and restores biochemical parameters in cholestatic preschoolers and children. The edible film is a new dosage form included in USP-NF 2023. The objective was to design edible UDCA films (25 and 50 mg of UDCA/film) for chronic oral administration to pediatric patients.

METHODS

Films were developed with mannuronic acid-rich alginate by casting. They were evaluated for 18 months-storage at 25 °C and 33.3% relative humidity (RH).

RESULTS

UDCA powder crystallinity decreased from 75% to 28-32% in UDCA films. Film water content decreased with increasing UDCA dose. Glass transition temperature (Tg) increased from ‒129.15ºC (UDCA powder) to ≈ ‒80ºC for UDCA films (33.3% RH), while 0% RH UDCA powder (80% crystallinity) had not Tg. Film-FTIR spectra demonstrated that UDCA particles were buried or coated by the alginate film network. Films showed homogeneous UDCA distribution, adequate tensile strength, rapid swelling and disintegration (43-58 s), and UDCA content within USP specifications for 18 months.

CONCLUSIONS

Amorphous systems like these films can improve solubility and oral bioavailability of poorly water-soluble UDCA. Moreover, flexible alginate films ensure not only UDCA stability but also treatment adherence for pediatric oral simple administration given also the alginate taste-masking properties.