Irinotecan (CPT-11) is used to treat advanced colorectal cancer as an intravenous therapy. Depending on pH, CPT-11 exists in either a lactone (active) or carboxylate (inactive) form, or both. In this investigation, the feasibility for systemic delivery of CPT-11 through the buccal route was evaluated. Permeation of CPT-11 across porcine buccal mucosa was studied in vitro using side-by-side flow through diffusion cells at 37°C. Experiments were performed over a pH range from 4 to 9, and the permeability of both the lactone and carboxylate forms of CPT-11 was measured. CPT-11 steady state flux was determined over a range of donor concentrations at pH 4 (0.5, 1, 5, 10, 15, 20 mg/ml) and pH 6.8 (0.5, 5, 10 mg/ml). Steady state flux increased linearly with increasing donor concentration of CPT-11 at pH 4 (r2 = 0.9935) and at pH 6.8 (r2 = 0.9886). CPT-11 permeability was independent of pH, although the distribution coefficient increased with increasing pH. Estimates of permeability for the lactone and carboxylate forms were 4.16 × 10−5 cm/s and 2.6 × 10−5 cm/s, respectively. These calculated permeability values were in agreement with the in vitro experimental data. Overall, CPT-11 was found to permeate through porcine buccal mucosa via passive diffusion. CPT-11 permeability was independent of pH, suggesting that the compound was transported mainly via a paracellular route. Overall, the results of this research suggest that the buccal route is a potential extravascular mode of delivery for CPT-11.

Shah, V., Bellantone, R. D. A., Taft, D. R., Evaluating the Potential for Delivery of Irinotecan via the Buccal Route: Physicochemical Characterization and In Vitro Permeation Assessment Across Porcine Buccal Mucosa, <<AAPS PHARMSCITECH>>, 2016; (Giugno): 1-8. [doi:10.1208/s12249-016-0578-z] [http://hdl.handle.net/10807/91619]

Evaluating the Potential for Delivery of Irinotecan via the Buccal Route: Physicochemical Characterization and In Vitro Permeation Assessment Across Porcine Buccal Mucosa

Vidhi; Bellantone
;
2016

Abstract

Irinotecan (CPT-11) is used to treat advanced colorectal cancer as an intravenous therapy. Depending on pH, CPT-11 exists in either a lactone (active) or carboxylate (inactive) form, or both. In this investigation, the feasibility for systemic delivery of CPT-11 through the buccal route was evaluated. Permeation of CPT-11 across porcine buccal mucosa was studied in vitro using side-by-side flow through diffusion cells at 37°C. Experiments were performed over a pH range from 4 to 9, and the permeability of both the lactone and carboxylate forms of CPT-11 was measured. CPT-11 steady state flux was determined over a range of donor concentrations at pH 4 (0.5, 1, 5, 10, 15, 20 mg/ml) and pH 6.8 (0.5, 5, 10 mg/ml). Steady state flux increased linearly with increasing donor concentration of CPT-11 at pH 4 (r2 = 0.9935) and at pH 6.8 (r2 = 0.9886). CPT-11 permeability was independent of pH, although the distribution coefficient increased with increasing pH. Estimates of permeability for the lactone and carboxylate forms were 4.16 × 10−5 cm/s and 2.6 × 10−5 cm/s, respectively. These calculated permeability values were in agreement with the in vitro experimental data. Overall, CPT-11 was found to permeate through porcine buccal mucosa via passive diffusion. CPT-11 permeability was independent of pH, suggesting that the compound was transported mainly via a paracellular route. Overall, the results of this research suggest that the buccal route is a potential extravascular mode of delivery for CPT-11.
Inglese
Shah, V., Bellantone, R. D. A., Taft, D. R., Evaluating the Potential for Delivery of Irinotecan via the Buccal Route: Physicochemical Characterization and In Vitro Permeation Assessment Across Porcine Buccal Mucosa, <<AAPS PHARMSCITECH>>, 2016; (Giugno): 1-8. [doi:10.1208/s12249-016-0578-z] [http://hdl.handle.net/10807/91619]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/91619
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 7
social impact