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

Abstract

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 (Papp crystalline VAR = 6.83 × 10−6 cm/s vs. Papp 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 (Papp amorphous VAR = 8.75 × 10−6 cm/s vs. Papp 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.

Vardenafil Oral Dispersible Films (ODFs) with Advanced Dissolution, Palatability, and Bioavailability

“…Similar results were reported elsewhere with different excipients. Enhancement of vardenafil solubility was also reported with other hydrophilic carriers such as hydroxypropyl methyl cellulose (HPMC) and β-cyclodextrin, Complete amorphization of vardenafil was obtained at 1:1 and 1:5 weight ratios using the freeze-drying technique, improving solubility by 1.44-fold [ 17 ].…”

Amorphous Form of Carvedilol Phosphate—The Case of Divergent Properties

“…The observed improvement in solubility in combination with Pluronic ® F-127 can be attributed to the dispersion of amorphous API, eliminating the physical hindrance of the hard, solvent-impermeable API surface. Improved wettability translates into more significant CVD contact with the medium used, significantly affecting the obtained dissolution rate [52]. Carvedilol phosphate belongs to the 2nd BCS group characterized by poor solubility, limiting bioavailability, and good permeability through the biological membrane system.…”

“…The observed improvement in solubility in combination with Pluronic ® F-127 can be attributed to the dispersion of amorphous API, eliminating the physical hindrance of the hard, solvent-impermeable API surface. Improved wettability translates into more significant CVD contact with the medium used, significantly affecting the obtained dissolution rate [ 52 ].…”

Cellulosic Polymers for Enhancing Drug Bioavailability in Ocular Drug Delivery Systems

“…For example, Benzalkonium chloride alters the ocular barrier, but it has a toxic effect when used for several days by accumulating in the cornea [89] and EDTA acts by altering the tight junction of superficial cells and cause paracellular transport of the drug. Cyclodextrin, by complexing with the drug, solubilizes the lipophilic molecules [90] and results in increased permeation [91]. The colloidal system provides controlled drug release and prolonged pharmacological effects.…”