Combinations of Freeze-Dried Amorphous Vardenafil Hydrochloride with Saccharides as a Way to Enhance Dissolution Rate and Permeability

• Main Authors: Gabriela Wiergowska (Author), Dominika Ludowicz (Author), Kamil Wdowiak (Author), Andrzej Miklaszewski (Author), Kornelia Lewandowska (Author), Judyta Cielecka-Piontek (Author)
• Format: Book
• Published: MDPI AG, 2021-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/ph14050453; 1424-8247
• Keywords: vardenafil hydrochloride; amorphous dispersion; apparent solubility; permeability; Medicine; R; Pharmacy and materia medica; RS1-441
• Source: Pharmaceuticals, Vol 14, Iss 5, p 453 (2021)

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_{app crystalline VAR} = 6.83 × 10⁻⁶ cm/s vs. P_{app amorphous VAR} = 8.75 × 10⁻⁶ cm/s) was observed, especially for its combinations with β-CD in the ratio of 1:5-more than 1.5-fold increase (P_{app amorphous VAR} = 8.75 × 10⁻⁶ cm/s vs. P_{app amorphous VAR:β-CD 1:5} = 13.43 × 10⁻⁶ 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.