title: 3D printing of tablets containing multiple drugs with defined release profiles.
abstract: We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent 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: D002216:Captopril / Q000008:administration & dosage; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D016503:Drug Delivery Systems / Q000295:instrumentation*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005913:Glipizide / Q000008:administration & dosage; D006801:Humans; D009543:Nifedipine / Q000008:administration & dosage; D057285:Precision Medicine / Q000295:instrumentation*; D066330:Printing, Three-Dimensional / Q000295:instrumentation*; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000295:instrumentation*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005079:Excipients; D002216:Captopril; D009543:Nifedipine; D005913:Glipizide
keywords: 3D printing; Captopril (PubChem CID: 44093); Glipizide (PubChem CID: 3478); Multi-active tablets; Nifedipine (PubChem CID: 4485); Osmotic pump; Personalised medicine; Sustained release