Impact of polymeric excipient on cocrystal formation via hot-melt extrusion and subsequent downstream processing

Int J Pharm. 2019 Jul 20:566:745-755. doi: 10.1016/j.ijpharm.2019.06.031. Epub 2019 Jun 15.

Abstract

Pharmaceutical cocrystals have gained increasing interest due to their potential to modify the physicochemical properties of drugs. Herein, a 1:1 cocrystal of ibuprofen (IBU) as a BCS class II active pharmaceutical ingredient (API) and nicotinamide as coformer was produced using a hot-melt extrusion (HME) process. The effect of process parameters such as barrel temperature and screw speed were studied. It was shown that the addition of polymeric excipient such as soluplus (Sol) decreases the cocrystallization temperature by enhancing the interaction between API and coformer. In order to study the effect of cocrystallization on the tableting properties of IBU-NIC cocrystal, 5 different formulations of pure IBU, IBU-NIC cocrystal, IBU-NIC physical mixture, IBU-NIC-Sol physical mixture and IBU-NIC-Sol cocrystal were tableted by a compaction simulator. Tabletability, compactibility and compressibility were investigated. The sample with IBU-NIC-Sol cocrystal formulation outperformed all the other formulations in terms of tabletability, compactibility and compressibility. Interestingly, this sample was even superior to the IBU-NIC cocrystal sample which verified the advantageous effect of the presence of an excipient. Moreover, dissolution test confirmed a noticeable increase in the dissolution of not only the cocrystal samples but even the physical mixtures of IBU and NIC compared with pure IBU.

Keywords: Cocrystal; Compactibility; Compaction triangle; Compressibility; Downstream processing; Hot-melt extrusion; Tabletability.

MeSH terms

  • Crystallization
  • Drug Liberation
  • Excipients / chemistry*
  • Hot Melt Extrusion Technology
  • Ibuprofen / chemistry*
  • Niacinamide / chemistry*
  • Polyethylene Glycols / chemistry*
  • Polyvinyls / chemistry*
  • Tablets

Substances

  • Excipients
  • Polyvinyls
  • Tablets
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Niacinamide
  • Polyethylene Glycols
  • Ibuprofen