title: 3D printing of five-in-one dose combination polypill with defined immediate and sustained release profiles.
abstract: We have used three dimensional (3D) extrusion printing to manufacture a multi-active solid dosage form or so called polypill. This contains five compartmentalised drugs with two independently controlled and well-defined release profiles. This polypill demonstrates that complex medication regimes can be combined in a single personalised tablet. This could potentially improve adherence for those patients currently taking many separate tablets and also allow ready tailoring of a particular drug combination/drug release for the needs of an individual. The polypill here represents a cardiovascular treatment regime with the incorporation of an immediate release compartment with aspirin and hydrochlorothiazide and three sustained release compartments containing pravastatin, atenolol, and ramipril. X-ray powder diffraction (XRPD) and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) were used to assess drug-excipient interaction. The printed polypills were evaluated for drug release using USP dissolution testing. We found that the polypill showed the intended immediate and sustained release profiles based upon the active/excipient ratio used.
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Shaban A
authors.initials: SA
authors.lastname: Khaled
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Burley
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Morgan R
authors.initials: MR
authors.lastname: Alexander
authors.affiliation: Division of Drug Delivery and Tissue Engineering, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham NG7 2RD, UK. Electronic address: clive.roberts@nottingham.ac.uk.
authors.forename: Clive J
authors.initials: CJ
authors.lastname: Roberts
mesh_terms: D001241:Aspirin / Q000737:chemistry; D001262:Atenolol / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004338:Drug Combinations; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D006852:Hydrochlorothiazide / Q000737:chemistry; D033362:Powder Diffraction; D017035:Pravastatin / Q000737:chemistry; D066330:Printing, Three-Dimensional; D017257:Ramipril / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005079:Excipients; D013607:Tablets; D006852:Hydrochlorothiazide; D001262:Atenolol; D017035:Pravastatin; D017257:Ramipril; D001241:Aspirin
keywords: 3D printing; Aspirin (PubChem CID: 2244); Atenolol (PubChem CID: 2249); Hydrochlorothiazide (PubChem CID: 3639); Immediate release; Personalised medicine; Polypill; Pravastatin sodium (PubChem CID: 16759173); Ramipril (PubChem CID: 5362129); Sustained release