Hydroxypropyl-β-cyclodextrin functionalized calcium carbonate microparticles as a potential carrier for enhancing oral delivery of water-insoluble drugs

Abstract

The objective of the present study was to demonstrate that a novel hydroxypropyl-β-cyclodextrin functionalized calcium carbonate (HP-β-CD/CC) based amorphous solid dispersion (ASD) can be used to increase the solubility and oral bioavailability of water-insoluble drugs. Irbesartan (IRB) was selected as a model compound and loaded into the nanoporous HP-β-CD/CC matrix using an immersion method. The IRB-loaded HP-β-CD/CC formulation was characterized by various analytical techniques, such as specific surface area analysis, scanning electron microscopy (SEM), dynamic light scattering (DLS), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Analyses with PXRD and DSC confirmed that IRB was fully converted into the amorphous form in the nanopores of HP-β-CD/CC. From the solubility and dissolution tests, it was observed that the aqueous solubility and dissolution rate of IRB-loaded HP-β-CD/CC were increased significantly compared with those of pure IRB and IRB-loaded mesoporous silica. Likewise, the IRB-loaded HP-β-CD/CC formulation exhibited better absorption compared with that of the commercially available IRB capsules in beagle dogs. The mean peak plasma concentration (C_max) and the area under the mean plasma concentration–time curve (AUC_[0→48]) of IRB-loaded HP-β-CD/CC were 1.56- and 1.52-fold higher than that of the commercial product, respectively. Furthermore, the IRB-loaded HP-β-CD/CC formulation exhibited excellent stability against re-crystallization. These results clearly demonstrate that HP-β-CD/CC based porous ASD is a promising formulation approach to improve the aqueous solubility and the in vivo absorption performance of a water-insoluble compound like IRB.

Keywords:

• nanopore
• solid dispersion
• solubility
• dissolution rate
• bioavailability

Supplementary materials

Figure S1 Nitrogen adsorption/desorption isotherms of (A) HP-β-CD/CC and (B) SBA-16.

Note: Nitrogen adsorption isotherm (♦); nitrogen desorption isotherm (⋄).

Abbreviations: HP-β-CD/CC, hydroxypropyl-β-cyclodextrin functionalized calcium carbonate; SBA-16, Santa Barbara amorphous materials-16; STP, standard temperature and pressure.

Table S1 The materials used in the study

Acknowledgments

This work was financially supported by the National Science Foundation of China (No 81402879), the Natural Science Foundation of Jiangsu Province of China (No BK20140221), and Project for Excellent Talents of Xuzhou Medical College (No 53631309). We would like to thank Dr David Jack for ensuring that the document is free of language errors.

Disclosure

The authors report no conflicts of interest in this work.