(M1430-08-53) Development of Pediatric Immediate Release Mini-Tablet Formulation for a Novel FGFR Inhibitor Using Direct Compression and Functional Coating

Purpose: A novel fibroblast growth receptor (FGFR) inhibitor (X) is under clinical development for treatment of advanced solid tumors and skeletal disorders. Pediatric patients often experience difficulty swallowing conventional tablets, creating a need for flexible, age-appropriate oral formulations. This study focused on the development of an immediate release (IR) minitablet formulation of X, intended to be encapsulated and administered via sprinkling on soft foods. The objective was to create a formulation that maintains physical integrity during coating and handling while enabling rapid drug release upon ingestion.

Methods: Minitablets were prepared by direct compression employing conventional unit operations including weighing, dry blending, tableting, and fluid bed coating. Three different formulation approaches were evaluated for development of pediatric immediate-release formulations were. Formulation A was developed with 30% w/w microcrystalline cellulose (MCC) and 1% super disintegrant. Coating was applied using methacrylate-based polymer (EPO) at 10%, 15%, and 20% weight gains and minitablets were visually evaluated for disintegration behavior in food vehicles such as applesauce. The 20% coated tablets remained intact and were encapsulated (four mini-tablets per capsule) for dissolution testing. Formulation B was developed by increasing the disintegrant level to 2% w/w and utilizing a polyvinyl alcohol-based coating system (Opadry® AMB II White) at 10% weight gain. The compression parameters were optimized to get desired weight of 5 mg and hardness of 2.5 kp using 1.8mm multi-tip tooling. The compressed tablets were coated using Fluid bed coater. For Formulation C, the filler system was optimized to a 1:1 ratio of lactose monohydrate and microcrystalline cellulose (MCC), and coated with Opadry® at 10% weight gain. Minitablets from all formulations were evaluated for in vitro dissolution using USP apparatus Type I (Basket) in 500 mL of 0.5% CTAB or 2% SLS dissolved in 0,01 N HCl, maintained under stirring at 100 rpm and 37 °C. Visual evaluation of disintegration in common pediatric dosing vehicles (applesauce, banana and yogurt puree) was also assessed.

Results: After the evaluation of super disintegrant at two levels, (Batch #1 with 1% and Batch #2 at 2%), Batch #2 exhibited the fastest dissolution performance, with more than 75% drug release within 15 minutes was selected as the optimized concentration. As shown by the dissolution data in Fig. 1, the minitablets showed intact behavior in food vehicles and sustained coating integrity. As shown in Fig. 2, it exhibited faster drug release with >75% drug release within 15 minutes. As shown in Fig. 3. it demonstrated complete drug release within 30 minutes and full disintegration in apple sauce within the same period, confirming its suitability for pediatric sprinkle. Lastly, encapsulation of four mini tablets per capsule provided an accurate unit dose format for pediatric use.

Conclusion: A pediatric-friendly mini tablet formulation was successfully developed using direct compression and film coating. The final optimized formulation showed acceptable food compatibility and in vitro dissolution studies supported its suitability for sprinkle administration and advancement to clinical development for pediatric population