This projects goal is to develop an innovative cost-effective robotic platform for fast on-demand pharmacy production of pediatric drugs as individually tailored palatable gummy dosage forms. Medi- cation adherence is notoriously low among children due to difficulty swallowing pills and rejection of bad-tasting medications. Although some common pediatric drugs have flavored liquid forms, pediatric adherence is still low due to unacceptable taste and volume. Compound liquid formulations also contribute to the most common pe- diatric medical error incorrect dosing. Current mass manufacturing processes cannot economically provide the variety of flavors and doses needed in the comparatively smaller pediatric market. While existing gummy compounding practices are extremely slow, error-prone, and labor-intensive which limits their practice. This novel gummy production platform for pharmacies combines 3D printing with gummy-based phar- maceutical production for the first time. Vitaes automated compounding platform for on-demand custom dose tablet production provides a strong foundation for this project. Its capabilities will be expanded to support gummy production. The first target is a clonidine gummy to replace current oral compound suspensions. Aim 1 is to develop a flavored clonidine gummy formulation compatible with the robotic plat- forms extrusion process. The proposed chemical gummy base formula is starch-based, an ingredient widely used in food and drug production. We will optimize this base for use with two additional model drugs to ensure platform versatility. Then, a predefined set of flavors compatible with clonidine will be incorporated. A final for- mula will be selected based on the active pharmaceutical ingredients (APIs) stability, viscosity, and viscoelas- tic properties. Aim 2 is to develop algorithms for printing accurately dosed gummies. Existing 3D printing (3DP) software controls output by computing paths based on size and shape. However, producing correct drug doses depends on volume and mass of APIs and excipients. Therefore, mathematical algorithms will be devel- oped to translate the specified dose and characteristics of the starting material (e.g. concentration) into a pre- cise gummy size, shape, volume and path for robotic production via 3DP. Successful completion of this Phase I project will result in a clonidine gummy formulation that pharma- cies can compound with Vitaes automated platform and dispense to patients. Medication acceptance relating to taste can then be evaluated by pediatric patients. This project will also establish feasibility of formulating other drugs in the printable gummy base allowing Vitae to immediately test, verify and deploy additional gum- my drugs after completion. Designed for use in compounding and hospital pharmacies, the proposed robotic platform will fully automate the currently slow, manual extemporaneous preparation process, significantly in- creasing efficiency and reducing costs. Improving accessibility and affordability of tailored gummies would facil- itate large-scale studies to evaluate custom doses and improve critically lacking pediatric dosing guidelines.
Public Health Relevance Statement: PROJECT NARRATIVE Adherence to properly dosed medications is essential for successful treatment outcomes, but pediatric adherence is notoriously low and incorrect dosing is the most commonly reported error in pediatrics. There is a clear need for more palatable medications that accurately provide the range of doses needed by children, especially since taste is the most commonly reported reason for rejecting medication. This project will develop a novel robotic platform based on 3D printing technology to enable fast, on-demand pharmacy production of custom flavored palatable gummy medications with precise tailored doses required by children of all ages and sizes.
Project Terms: Address; Adherence; Age; Algorithmic Software; Algorithms; Azathioprine; base; Characteristics; Chemicals; Chemistry; Child; Childhood; Clonidine; comparative; Computer software; Construction Materials; cost; cost effective; Custom; Deglutition; density; design; Devices; dosage; Dosage Forms; Dose; Drug Delivery Systems; Drug Modelings; drug production; Ensure; Environment; Environmental Pollution; Excipients; experience; Flavoring; flexibility; Food production; Formulation; Foundations; Gel; Goals; Guidelines; Hand; Hospitals; Hour; improved; Individual; Industry; innovation; Instruction; Legal patent; liquid formulation; Liquid substance; Manuals; manufacturing process; mathematical algorithm; Medical Errors; medication compliance; Methods; Modeling; Motion; next generation; novel; Oral; Output; Palate; Patients; pediatric patients; Pediatrics; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacy facility; Phase; pill; Preparation; prevent; Printing; Process; Production; Property; prototype; Quality Control; Quickset; Reporting; robotic device; Robotics; Shapes; software development; Solid; Specific qualifier value; Starch; Sterility; Sum; Suspensions; System; Tablets; Tacrolimus; Taste Perception; Technology; Temperature; Testing; Time; Titrations; Translating; Treatment outcome; Viscosity; Work
