High-Boiled Lozenges of Prednisolone: proof of concept of Novel Paediatric Oral Dosage Form

INTRODUCTION The development of age-appropriate medicines remains a major challenge in paediatric pharmacotherapy. Prednisolone is widely prescribed in children for the treatment of inflammatory and immune-mediated disorders; however, currently available oral dosage forms of prednisolone — tablets, solutions, and syrups — are often associated with poor palatability, swallowing difficulties, and limited dosing flexibility [1, 2]. High-boiled lozenges (HBL) represent an attractive and largely unexplored paediatric-friendly alternative by combining ease of administration, taste-masking potential, and improved acceptability. The aim of this study was to develop an isomalt-based prednisolone HBL as a low-dose formulation suitable for paediatric use and to investigate the influence of different prednisolone incorporation pathways on the macroscopic appearance, content uniformity (Ph.Eur.), disintegration time, and dissolution in PBS pH 6.8. METHODS Isomalt (galenIQ™ 720 #L1214936U1; BENEO Palatinit GmbH, Obrigheim/Pfalz, Germany) and citric acid (Merck KGaA, Darmstadt, Germany) were used as excipients, and prednisolone (Tokyo Chemical Industry Co Ltd, Tokyo, Japan) as a model drug. Prednisolone HBLs (target dose of 5 mg/unit; 0.25 g/batch of 50 lozenges) were prepared using isomalt (99.3wt.%) and citric acid (0.5wt.%). Three drug incorporation scenarios were compared. Scenario 1: direct addition of prednisolone and citric acid as powders to the molten isomalt mass. Scenario 2: pre-dispersion of prednisolone and citric acid in purified water before isomalt incorporation. Scenario 3: pre-dissolution of prednisolone in ethanol 96% followed by addition to the molten mass. RESULTS A dose strength of 5 mg per lozenge was selected, corresponding to the minimum therapeutic adult oral dose and enabling flexible weight-based dosing in paediatric patients. All formulations produced slightly translucent glassy lozenges. Unit weight ranged from 2,3 ± 0,1 g (Av.±SD). Disintegration test showed mean disintegration times of 798±34, 740±31, and 777±17, for Scenario 1, 2, and 3, respectively. Dissolution test results shoved the distinct difference between the formulations. The speed and completeness of drug release increased from Scenario 1 to 2, and to 3. Content uniformity was improved in the same way. CONCLUSION This study introduces prednisolone HBLs as a novel age-appropriate dosage form designed to address key challenges in paediatric corticosteroid therapy. The prednisolone incorporation significantly influenced drug release, content uniformity, and almost didn’t influence the disintegration time. These findings support the further development of high-boiled lozenges as an innovative platform for paediatric oral drug delivery requiring low-dose administration and effective taste masking. REFERENCES 1. Yoo, O., Tang, E., Hossain, M. L., et al. (2024). The Development of a Chocolate-Based Chewable Tablet of Prednisolone—Enhancing the Palatability of Steroids for Pediatric Use. Pharmaceutics, 16(8), 1099. Retrieved from https://doi.org/10.3390/pharmaceutics16081099. 2. Mitchell, J. C., & Counselman, F. L. (2003). A taste comparison of three different liquid steroid preparations: prednisone, prednisolone, and dexamethasone. Academic emergency medicine, 10(4), 400-403.