Additive Manufacturing of a Point‐of‐Care “Polypill:” Fabrication of Concept Capsules of Complex Geometry with Bespoke Release against Cardiovascular Disease

Abstract

Polypharmacy is often needed for the management of cardiovascular diseases and is associated with poor adherence to treatment. Hence, highly flexible and adaptable systems are in high demand to accommodate complex therapeutic regimens. A novel design approach was employed to fabricate highly modular 3D printed 'polypill' capsules with bespoke release patterns for multiple drugs. Complex structures were devised using combined fused deposition modelling 3D printing aligned with hotfilling syringes. Two unibody highly modular capsule skeletons with 4 separate compartments were devised: i) concentric format: two external compartments for early release whilst two inner compartments for delayed release, or ii) parallel format: where non-dissolving capsule shells with free-pass corridors and dissolution rate-limiting pores were used to achieve immediate and extended drug releases, respectively. Controlling drug release was achieved through digital manipulation of shell thickness in the concentric format or the size of the rate limiting pores in the parallel format. Target drug release profiles were achieved with variable orders and configurations, hence confirming the modular nature with capacity to accommodate therapeutics of different properties. Projection of the pharmacokinetic profile of this digital system capsules revealed how the developed approach could be applied in dose individualization and achieving multiple desired pharmacokinetic profiles.

Three-dimensional Printing of Customized Bioresorbable Airway Stents

“…In combination with medical imaging techniques, three dimensional (3D) printing technologies [6][7][8][9][10][11][12][13] , such as digital light processing (DLP) 14 , provide enormous opportunities for rapid and affordable production of personalized medical devices [15][16][17][18][19] , including airway stents 5 . This specific manufacturing technology is based on the localized light-initiated photopolymerization of a liquid resin containing (macro)monomers 6,20 .…”

3D Printing as a Promising Tool in Personalized Medicine

“…The capsule shell composed of polyvinyl alcohol and polylactic acid. Customized release profiles were obtained through the alteration of shell thickness in the concentric configuration or size of rate limiting orifices in the parallel configuration ( 134 ).…”

<p>Moving the Dial on Heart Failure Patient Adherence Rates</p>

“…However, patients require different doses and combinations of medicines and a rigid formulation would only be suitable for a very limited number of patients. 11 One proposed solution is to use 3D printing as a way to quickly and easily manufacture personalized polypills at pharmacy level. 3D printing has the capability to create highly modular capsules which allow for bespoke drug release patterns by controlling concentric shell thickness or shell porosity.…”

“…10 These issues may be exacerbated for patients requiring polypharmacy (40-50% of elderly patients in high-income countries) where >25% of elderly patients have a chronic intake of 10+ medicines. 11,12 Polypharmacy can impact adherence through myriad drivers including increased financial burden, unwanted drugdrug interactions, and complex/difficult dosing regimens. Studies have shown that a patient's perceptions on the number of prescribed medications have a stronger correlation with low adherence than the actual number, making polypharmacy a complex issue to tackle.…”