Photocurable Bioinks for the 3D Pharming of Pharmaceutical Tablets
New technologies for the fabrication of on-demand oral dosage forms are needed in order to provide personalized medicine accessible to patients at pharmacies and point-of-care locations. 3D Pharming, the direct printing of pharmaceutical tablets, is an attractive technology towards the manufacture of oral dosage forms with controlled dosages, drug release kinetics, and the potential to combine multiple drugs into a single tablet. Powder bed 3D printing and fused deposition modeling (FDM) have been the two most explored 3D printing technologies towards the manufacture of personalized medicine. However, these techniques experience limitations in terms of printing speed and operation at high temperatures causing potential drug degradation, respectively. To overcome these limitations, the objective of this dissertation was to design a 3D Pharming system based on the inkjet printing of photocurable bioinks, capable of dispensing hydrophilic and hydrophobic APIs, with quick printing speeds at room temperature. The procedure included the dispensing of drug loaded bioinks onto blank preform tablets, their subsequent light induced polymerization, and the attachment of a preform cap to complete the oral dosage form.
This objective was achieved by 1) chemically manipulating hyaluronic acid to incorporate norbornene moieties into its backbone, resulting in a photoreactive biocompatible polymer to be used as the main component of a hydrophilic bioink; 2) designing a poly(ethylene glycol) based photocurable formulation for the dispensing of hydrophobic compounds; and 3) demonstrating the use of these bioinks towards the fabrication of combination therapies by creating a polypill including two drugs for the treatment of hypertension. The capacity of these bioinks for droplet formation was analyzed by calculating the inverse of the Ohnesorge number and the mechanical properties of the polymerized gels were assessed. Dissolution tests were performed on fabricated tablets containing the hydrophilic drug Ropinirole, Naproxen as a hydrophobic compound, and the combination of Lisinopril and Spironolactone within a polypill for the treatment of hypertension. Immediate and sustained release profiles were achieved for Ropinirole and Naproxen, respectively, demonstrating control over drug release kinetics. This work presents a new 3D Pharming technique with a special application towards drugs that achieve their pharmacological effect at low dosages.