Abstract
Objective: Pemigatinib is an active component in treatment of cholangiocarcinoma, but the low solubility and bioavailability of Pemigatinib limit its wide application. The aim of the present study was to prepare and evaluate supersaturable self-nanoemulsifying drug delivery systems (sSNEDDS) followed by investigating and comparing the pharmacokinetic profiles of Pemigatinib and Pemigatinib sSNEDDS in rat plasma by HPLC.
Methods: Pemigatinib loaded SNEDDS were obtained by dissolving drug in the isotropic mixture of oil, surfactant, and co-surfactant. The conventional SNEDDS were converted to sSNEDDS by precipitation method by using an experimented polymer. An appropriate high sensitivity and selectivity was applied to the comparison of plasma pharmacokinetics in Pemigatinib and Pemigatinib sSNEDDS using Entrectinib as an internal standard (IS).
Results: The droplet of sSNEDDS ranges from 166.78±3.14 to 178.86±1.24 nm with PDI 0.212–0.256, transmission electron microscopy images revealed the spherical shape of the nanodroplets, emulsification time was 15 secs when added to physiological fluids, percent transmittance of the diluted formulation was 99.12±0.46, and viscosity was 574±26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. Cmax of the sSNEDDS 3.52±0.13ng/ml was significant (P<0.05) as compared to the pure drug suspension formulation 2.82±0.42 ng/ml. The AUC0-t, AUC0–∞ of sSNEDDS was increased, while the Tmax and t1/2 was decreased. Moreover, the AUC value in the sSNEDDS group was significantly increased and the relative bioavailability was calculated to be 69% when compared with that of the Pemigatinib group.
Conclusion: These results concluded that Pemigatinib sSNEDDS when compared with pure drug after a single oral administration and the formulation modification of Pemigatinib into sSNEDDS can effectively enhance gastrointestinal absorption and relative bioavailability by improving solubility and dissolution rate.
Publisher
Innovare Academic Sciences Pvt Ltd