Ternary inclusion complex of docetaxel using ß-cyclodextrin and hydrophilic polymer: Physicochemical characterization and in-vitro anticancer activity

Abstract

Docetaxel, one of the highly effective anticancer drugs, cannot be delivered via the oral route to date due to lack of pharmacokinetic cooperation. Poor aqueous solubility of docetaxel is the major barrier for development of its oral formulation. So, the current research aspires to enhance its aqueous solubility with the aid of a complexation technique using β-cyclodextrin. Therefore, binary and ternary complexes of docetaxel were prepared with β-cyclodextrin and hydroxypropyl methylcellulose (HPMC) E5 by the freeze-drying technique. Different polymers were screened as ternary agents and HPMC E5 was selected for the final formulation based on its stability constant and complexation efficiency. When compared to pure docetaxel, both binary and ternary inclusion complexes demonstrated 12.77 and 17.02 times rise in aqueous solubility and 2.22-and 2.48-fold enhanced drug release, respectively. Differential scanning calorimetry, powder X-ray diffractometry, Fourier transform infrared, and scanning electron microscopic examinations all confirmed the complex formation. On MCF -7 cell lines, in-vitro anticancer activity investigations of the pure drug and its prepared complexes were carried out, with the results proving 1.66 times enhanced activity with complexes over docetaxel alone.

Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity

“…Fatmi et al [74] obtained a ternary inclusion complex of camptothecin:PEG 6000:cyclodextrins by solvent evaporation method. In another study, Mane et al [75] prepared docetaxel:HPMC:βCD solid inclusion complexes via the freeze-drying method. Thiry et al [76] used hot-melt extrusion (HME) to form itraconazole:Soluplus ® :cyclodextrin ternary inclusion complexes.…”

“…The formation of inclusion complexes is possible through the emergence of hydrophobic interactions, hydrogen bonding, or van der Waals forces [75,93].…”

“…As predicted by PrankWeb, the AchE active site contained TYR 68 , ASP 70 , TYR 73 , THR 79 , TRP 82 , ASN 83 , GLY 116 , GLY 117 , GLY 118 , TYR 120 , SER 121 , GLY 122 , LEU 126 , GLU 198 , SER 199 , TRP 282 , LEU 285 , SER 289 , PHE 291 , ARG 292 , PHE 293 , TYR 333 , PHE 334 , TYR 337 , TRP 435 , HIS 443 , GLY 444 , and TYR 445 . The BChE's active pocket contained: ASP 67 , GLY 75 , SER 76 , TRP 79 , ASN 80 , GLY 112 , GLY 113 , GLY 114 , GLN 116 , THR 117 , GLY 118 , TYR 125 , GLU 194 , SER 195 , TRP 228 , PRO 282 , LEU 283 , SER 284 , VAL 285 , ALA 325 , PHE 326 , TYR 329 , PHE 393 , TRP 425 , HIS 433 , GLY 434 , and TYR 435 .…”