A Novel Desloratadine-Benzoic Acid Co-Amorphous Solid: Preparation, Characterization, and Stability Evaluation

Abstract

Low physical stability is the limitation of the widespread use of amorphous drugs. The co-amorphous drug system is a new and emerging method for preparing a stable amorphous form. Co-amorphous is a single-phase amorphous multicomponent system consisting of two or more small molecules that are a combination of drugs or drugs and excipients. The co-amorphous system that uses benzoic acid (BA) as an excipient was studied to improve the physical stability, dissolution, and solubility of desloratadine (DES). In this study, the co-amorphous formation of DES and BA (DES–BA) was prepared by melt-quenching method and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). Dissolution, solubility, and physical stability profiles of DES–BA were determined. The DES crystals were converted into DES–BA co-amorphous form to reveal the molecular interactions between DES and BA. Solid-state analysis proved that the co-amorphous DES–BA system (1:1) is amorphous and homogeneous. The DSC experiment showed that the glass transition temperature (Tg) of tested DES–BA co-amorphous had a higher single Tg compared to the amorphous DES. FTIR revealed strong interactions, especially salt formation. The dissolution rate and solubility of co-amorphous DES–BA (1:1) obtained were larger than the DES in crystalline form. The PXRD technique was used to assess physical stability for three months at 40 °C with 75% RH. The DES–BA co-amorphous system demonstrated better physical stability than a single form of amorphous DES. Co-amorphous DES–BA has demonstrated the potential for improving solid-state stability, as the formation of DES–BA co-amorphous salt increased solubility and dissolution when compared to pure crystalline DES. This study also demonstrated the possibility for developing a DES–BA co-amorphous system toward oral formulations to improve DES solubility and bioavailability.

Evaluation of Thermal-Induced Polymorphic Transformation on Desloratadine and Desloratadine-Benzoic Acid Salt

“…Furthermore, heating at 190 o C showed a widening of the spectra peak for DES and DES-BA salt, which showed decreased crystallinity and an increased amorphous phase. 26 This was also supported by the PXRD and DSC data above, which showed crystallinity decrease. Based on these data, heating could have initiated the amorphous formation and polymorphic transformation but did not change the chemical structure of DES.…”

Preparation of Spray Dried Coamorphous Solids to Improve the Solubility and Dissolution Rate of Atorvastatin Calcium

“…Methanol was used to prepare the feed solution of the spray drying process because it dissolves AC and coformers (INA and MA) quite well. Furthermore, the use of methanol as a solvent in the formation of active coamorphous pharmaceutical compounds has been stated in several literature [10,20,29,30].…”

Applying Supercritical Fluid Technology to Prepare Ibuprofen Solid Dispersions with Improved Oral Bioavailability

“…Therefore, we further adopted DSC characterization and molecular simulation to prove that the drug can be spontaneously loaded in the carrier to form a stable system (△G < 0). IBU, indeed, converted to amorphous, which is beneficial to the dissolution of the drug [ 27 , 28 , 29 ]. In the supercritical CO 2 , hydrogen bond dimers formed between the molecules of IBU.…”