Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pediatric Formulations

Background:

• Poor patient compliance with 4-phenylbutyrate (PB) treatment for urea cycle disorders (UCDs) persists despite taste-masked formulations.
• Orally disintegrating tablets (ODTs) offer improved compliance, particularly for pediatric and dysphagic populations.
• Cyclodextrins (CDs) have demonstrated potential for taste-masking PB.

Purpose of the Study:

• To develop a novel cyclodextrin (CD)-based orally disintegrating tablet (ODT) formulation of 4-phenylbutyrate (PB).
• To evaluate the feasibility of this ODT formulation as an alternative for UCD patients, especially pediatric and dysphagic individuals.

Main Methods:

• Characterization of PB-CD interactions using X-ray diffraction, SEM, dissolution, and stability studies.
• Formulation of lyophilized PB-CD systems into ODTs via wet granulation.
• Evaluation of ODT physical characteristics, disintegration time, and pH stability.

Main Results:

• The developed αCD-based ODT exhibited a disintegration time of 28 seconds.
• The formulation achieved a suitable pH (≈5.5) for effective PB-CD complexation and taste masking.
• ODTs demonstrated adequate physical properties and good storage stability.

Conclusions:

• A novel cyclodextrin-based orally disintegrating tablet formulation for 4-phenylbutyrate has been successfully developed.
• This ODT formulation shows promise as an improved alternative for urea cycle disorder patients, particularly pediatric and dysphagic individuals, by enhancing compliance.