Effect of porcine pancreatic α-amylase on dexamethasone release from aqueous solution containing natural γ-cyclodextrin

  • Int J Pharm. 2020 Jul 30:585:119452. doi: 10.1016/j.ijpharm.2020.119452.
Suppakan Sripetch  1 ,  Phatsawee Jansook  2 ,  Thorsteinn Loftsson  3
Affiliations
  • 1. Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland; Oculis ehf, Alfheimar 74, 6th Floor, 104 Reykjavik, Iceland.
  • 2. Oculis ehf, Alfheimar 74, 6th Floor, 104 Reykjavik, Iceland; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Wangmai, Pathumwan, Bangkok 10330, Thailand.
  • 3. Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland; Oculis ehf, Alfheimar 74, 6th Floor, 104 Reykjavik, Iceland. Electronic address: [email protected].
PMID: 32464233 DOI: 10.1016/j.ijpharm.2020.119452
Abstract

Dexamethasone release from natural γ-cyclodextrin (γCD) complexes was investigated in presence of porcine pancreatic α-amylase (PPA). The phase-solubility of dexamethasone in aqueous γCD solutions was determined, PPA degradation of γCD was investigated, and permeation studies were performed in simulated tear fluid. The phase-solubility profile was of Bs type and the stability constant (K1:1) of the dexamethasone/γCD complex determined from the initial linear section of the profile was relatively high or 12887 M-1. The high K1:1 value indicates that dexamethasone has high affinity for γCD under the test condition. From the PPA catalyzed γCD degradation studies the Michaelis-Menten constant (Km) and Vmax were determined to be 3.24 mM and 9.79 × 10-3 mM/min, respectively. The permeation studies performed at low γCD concentrations, showed that dexamethasone is released from the complex solutions at faster rate when PPA was present than when no PPA was present.

Keywords
Complexation; Dexamethasone; Hydrolysis; Porcine pancreatic α-amylase; γ-Cyclodextrin.
Products