Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability
To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients-hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)-were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Book |
| Published: |
MDPI AG,
2021-05-01T00:00:00Z.
|
| Subjects: | |
| Online Access: | Connect to this object online. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | To improve physicochemical properties of vardenafil hydrochloride (VAR), its amorphous form and combinations with excipients-hydroxypropyl methylcellulose (HPMC) and β-cyclodextrin (β-CD)-were prepared. The impact of the modification on physicochemical properties was estimated by comparing amorphous mixtures of VAR to their crystalline form. The amorphous form of VAR was obtained as a result of the freeze-drying process. Confirmation of the identity of the amorphous dispersion of VAR was obtained through the use of comprehensive analysis techniques-X-ray powder diffraction (PXRD) and differential scanning calorimetry (DSC), supported by FT-IR (Fourier-transform infrared spectroscopy) coupled with density functional theory (DFT) calculations. The amorphous mixtures of VAR increased its apparent solubility compared to the crystalline form. Moreover, a nearly 1.3-fold increase of amorphous VAR permeability through membranes simulating gastrointestinal epithelium as a consequence of the changes of apparent solubility (P<sub>app crystalline VAR</sub> = 6.83 × 10<sup>−6</sup> cm/s vs. P<sub>app amorphous VAR</sub> = 8.75 × 10<sup>−6</sup> cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5-more than 1.5-fold increase (P<sub>app amorphous VAR</sub> = 8.75 × 10<sup>−6</sup> cm/s vs. P<sub>app amorphous VAR:β-CD 1:5</sub> = 13.43 × 10<sup>−6</sup> cm/s). The stability of the amorphous VAR was confirmed for 7 months. The HPMC and β-CD are effective modifiers of its apparent solubility and permeation through membranes simulating gastrointestinal epithelium, suggesting a possibility of a stronger pharmacological effect. |
|---|---|
| Item Description: | 10.3390/ph14050453 1424-8247 |