New dosage forms are needed to address the shortcomings of current practice with regard to administration of medications to pediatric populations. Specifically, in the absence of pediatric-specific products - formulations that are both palatable (to ensure compliance) and titratable (to meet the weight/surface area- appropriate dosage) - providers either utilize adult-approved liquid formulations or manipulate available products to create extemporaneous formulations (e.g., by crushing a tablet). Liquid suspensions, while titratable and largely preferred by children over tablets and capsules, are often poorly palatable and thus suffer from poor compliance. Ad-hoc formulations can also alter the performance and risk the likelihood of under or over-dosing. Orbis Biosciences's has developed a free-flowing drug-loaded microcapsule-based powder that will taste-mask bitter pharmaceutical actives during ingestion and exhibit complete dosage form dissolution in the gastrointestinal tract. This microcapsule platform is made possible by utilizing Precision Particle Fabrication (PPF) to place a pH-responsive shell over a solid-dispersed core of poorly water-soluble drug in a water-free, single step process. The first product to use Orbis's microcapsule approach to taste masking will be ORB-101, a prednisone-loaded microcapsule formulation. Upon successful FDA approval, ORB-101 will compete with oral liquid formulations or prednisone and prednisolone, products that suffer from poor palatability. Under the Phase I SBIR work, Orbis successfully developed two formulations, ORB-101 and ORB-102, containing prednisone and ritonavir, respectively. The microcapsule powders were able to: (1) reduce the presence of prednisone and ritonavir in neutral dissolution medium at 2 minutes by 55 and 92% respectively, compared to the RLD syrups for these two drugs, and (2) still exhibit 100% dissolution by 30 minutes when placed in acidic medium. The objective of this Phase II proposal is to optimize the prednisone formulation (ORB-101) into a shelf-stable powder in vitro (Aim 1), verify it's superior palatability compared to the RLD in a human taste screening (Aim 2), and demonstrate its bioequivalence to the RLD in a human pharmacokinetic study (Aim 3). The completion of this Phase II SBIR program will facilitate the efficient and timely submission of an IND filing to the FDA (Phase III SBIR) and have an immediate and lasting impact on the best practices for treating prednisone-responsive pediatric disorders by: (1) establishing the improved palatability or ORB-101 in the first human trials while, (2) readying ORB-101 and the PPF platform on which it is based for a co- development agreement or venture capital funding.
Inadequate pediatric pharmaceutical formulations impair effective treatment of diseases in children due to poor compliance, extemporaneous formulations, and dangerous medication errors. At the foundation of the problem are palatability, accurate dosing, and age-appropriate dosage format challenges. Development of a user-friendly, inexpensive development platform for pediatric reformulation of existing adult drug products to administer taste-masked active pharmaceutical ingredients (APIs) with controlled release rates is needed. Using prednisone as a model foul-tasting API, this project aims to develop pediatric-specific formulations using Precision Particle Fabrication technology that are palatable, age-appropriate, and allow for accurate dosing as a means to safer pediatric medications and better compliance.