3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy

Abstract

Therapy for Parkinson’s disease is quite challenging. Numerous drugs are available for symptomatic treatment, and levodopa (LD), in combination with a dopa decarboxylase inhibitor (e.g., benserazide (BZ)), has been the drug of choice for years. As the disease progresses, therapy must be supplemented with a dopamine agonist (e.g., pramipexole (PDM)). Side effects increase, as do the required dose and dosing intervals. For these specific requirements of drug therapy, the 3D printing method fused deposition modelling (FDM) was applied in this study for personalized therapy. Hot melt extrusion was utilized to produce two different compositions into filaments: PDM and polyvinyl alcohol for rapid drug release and a fixed combination of LD/BZ (4:1) in an ethylene-vinyl acetate copolymer matrix for prolonged drug release. Since LD is absorbed in the upper gastrointestinal tract, a formulation that floats in gastric fluid was desired to prolong API absorption. Using the FDM 3D printing process, different polypill geometries were printed from both filaments, with variable dosages. Dosage forms with 15–180 mg LD could be printed, showing similar release rates (f2 > 50). In addition, a mini drug delivery dosage form was printed that released 75% LD/BZ within 750 min and could be used as a gastric retentive drug delivery system due to the floating properties of the composition. The floating mini-polypill was designed to accommodate patients’ swallowing difficulties and to allow for individualized dosing with an API release over a longer period of time.

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

“…For example, lisinopril and amlodipine for hypertension, indapamide as a diuretic, and rosuvastatin for dyslipidemia were combined within the same solid dosage form. Filaments were prepared by hot-melt extrusion using PVA and sorbitol as excipients using distilled water as a temporary coplasticizer to reduce the extrusion temperature from 170 to 90 °C [ 62 ].…”

Orodispersible Films—Current State of the Art, Limitations, Advances and Future Perspectives

“…The innovative approach is that patients can easily scan the QR-encoded ODF using a smartphone and obtain information about the drug. 3D printing is also used for the preparation of tablets in the field of personalized therapy [ 57 , 62 ].…”

A Review of the Benefits 3D Printing Brings to Patients with Neurological Diseases

“…Windoft et al [ 58 ] developed an oral dosage form with pramipexole (PDM), LD, and BZ with FDM 3D-printing process, aimed at patients with PD. Hot-melt extrusion created all the filaments with 1.85 mm diameter for the FDM printing.…”

“…Different geometries can impact the surface area-to-volume ratio. In this case, hollow mini cylinders were printed which were thought to have been easier to swallow for patients with PD [ 58 ]. Due to the low density of the formulation, the tablet had a floating property which resulted in prolonged gastric residence time.…”