Investigation of the effect of colloidal structures formed during lipolysis of lipid-based formulation on exemestane permeability using the in vitro lipolysis-permeation model

Timur B., Yılmaz Usta D., Teksin Z. S.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.77, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 77
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.jddst.2022.103797
  • Dergi Adı: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Anahtar Kelimeler: Lipid-based formulation, Self-nanoemulsifying drug delivery systems, Exemestane, In vitro digestion, Supersaturation, Permeation, DRUG-DELIVERY SYSTEM, WATER-SOLUBLE DRUGS, OPTIMIZATION, TESTS, BIOAVAILABILITY, PRECIPITATION, ESTABLISHMENT, PERFORMANCE, MECHANISMS, PREDICTION
  • Gazi Üniversitesi Adresli: Evet

Özet

This study aimed to examine the effect of colloidal structures forming and changing with dispersion and digestion of lipid-based formulation (LBF) on the permeability of exemestane (EXE), a poorly water-soluble drug. Self-nanoemulsifying drug delivery system (SNEDDS), one of the LBF, was developed using Imwitor (R) 988, Kolliphor (R) RH 40, and Labrasol (R) according to the solubility study and optimized using Box-Behnken Design. The EXE-loaded SNEDDS formulation has a 14.46 +/- 0.23 nm droplet size with a 0.119 +/- 0.053 polydispersity index. EXE was loaded into SNEDDS at 15 mg/g. In vitro digestion was conducted to investigate the EXE permeability at the digestion medium and the flux of EXE through a dialysis membrane and porcine intestinal tissue was assessed with the permeability step. In vitro digestion study revealed that the SNEDDS formulation retained the solubi-lization of EXE and showed moderate supersaturation. The permeation of EXE through the dialysis membrane was observed that the EXE amount on the acceptor side was similar during different digestion phases, but the permeation of EXE through porcine intestinal tissue was slightly different during different digestion phases and EXE permeability was higher at 60 min of digestion although statistically not significant. However, EXE pre-cipitation was observed since the solvation capacity of colloidal structures was slightly decreased at 60 min of digestion. It can be explained by the fact that EXE re-dissolved and increased the free fraction, increasing permeability. This study showed that the drug precipitation in the digestion study does not always result in low permeation and minor differences could be observed more evident in the porcine intestine tissue.