The Development of Minitablets for a Pediatric Dosage Form for a Combination Therapy.

Minitablets are an appealing option for an age-appropriate pediatric dosage form. In particular, for combination therapies where multiple active ingredients are dosed simultaneously, the use of minitablets will enable independent adjustments of each dose. The work presented describes the development of Compound A and Compound B minitablets for a combination therapy. Since both actives are formulated as spray dried amorphous solid dispersions (ASDs) due to low solubility of their crystalline forms, the choice of minitablets for the pediatric dosage form allows the application of the same formulation strategy across different age groups. To address the potential need for taste-masking, an ethylcellulose-hydroxypropyl cellulose coating system was developed. In-vitro performance testing was conducted to guide coating development and to ensure proper taste-masking without slowing down API dissolution in the GI tract that can negatively impact exposures. As a result, the exposure of orally dosed coated tablets was comparable to those of uncoated minitablets in the canine model. The work presented can serve as a case study on how minitablets can be designed and developed as an appropriate pediatric dosage form for a combination therapy comprised of ASD of active ingredients.