Dissolution rate enhancement of loratadine in polyvinylpyrrolidone K-30 solid dispersions by solvent methods

• Published in: Powder technology 2013-02, Vol.235, p.532-539
• Main Authors: Frizon, Fernando, Eloy, Josimar de Oliveira, Donaduzzi, Carmen Maria, Mitsui, Márcia Lina, Marchetti, Juliana Maldonado
• Format: Article
• Language: English
• Subjects: Applied sciences; Bioavailability; biopharmaceuticals; Chemical engineering; differential scanning calorimetry; Dispersions; Dissolution; Drugs; Evaporation; Exact sciences and technology; Fourier transform infrared spectroscopy; hydrophilicity; light scattering; Loratadine; Miscellaneous; particle size; particle size distribution; Polyvinylpyrrolidone; PVP K-30; Rotary evaporation; scanning electron microscopy; Solid dispersion; Solid-solid systems; Solubility; Solvents; Spray-drying; surface area; temperature; thermogravimetry; water solubility; wettability; X-ray diffraction
• ISSN: 0032-5910; 1873-328X
• DOI: 10.1016/j.powtec.2012.10.019

Poorly water soluble drugs tend to have low bioavailability, however, this can be improved by several methods. One of the most promising strategies is the employment of solid dispersions to increase water solubility and enhance oral bioavailability of these drugs. Nonetheless, the mechanisms of solid dispersion formation may influence the solid-state characteristics and thus the dissolution profile. In this study, rotary evaporation and spray-drying solvent evaporation techniques were used to produce solid dispersions of the anti-allergenic loratadine, a class II drug in the Biopharmaceutical Classification System, with the hydrophilic carrier polyvinylpyrrolidone K-30. Thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, particle size distribution by light scattering, solubility at different pHs, and dissolution profile experiments were carried out to evaluate the solid dispersions and physical mixtures. Results showed an increase in solubility, especially in acid medium, where the drug is protonated, and an enhancement in dissolution profiles, following first order kinetic, of solid dispersions manufactured by both the rotary evaporation and the spray-drying methods. Both methods proved to be equally adequate, when compared to physical mixtures. This is a consequence of particle size reduction, increased wettability due to intimate contact of the drug with the hydrophilic matrix, increased surface area, and the conversion of the crystalline to the amorphous state, which proved to be stable after 6months at room temperature. Loratadine is a drug used to treat allergy, however its low water solubility limits the bioavalability. In this paper, we used solid dispersions with a hydrophilic polymer as a strategy to increase loratadine water solubility, using solvent methods. Solid dispersion formation resulted in increased water solubility and enhanced dissolution of the drug in comparison to the physical mixture. [Display omitted] ► Spray-drying and rotary evaporation produced solid dispersions of loratadine in PVP. ► Properties of loratadine in solid dispersions differed from physical mixtures. ► Loratadine in solid dispersions was converted from crystalline to amorphous form. ► Hydrogen bonding between drug and carrier could not be detected. ► Solid dispersions improved solubility and dissolution rate of loratadine.