Synthesis and Characterization of a New Norfloxacin/Resorcinol Cocrystal with Enhanced Solubility and Dissolution Profile

Abstract

A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values.

Solubility and permeability enhancement of BCS class IV drug ribociclib through cocrystallization

“…Resorcinol has been used as a coformer to improve the dissolution, solubility and stability of drug cocrystals. 24–26…”

“…Resorcinol has been used as a coformer to improve the dissolution, solubility and stability of drug cocrystals. [24][25][26] 2.3. Single crystal X-ray diffraction X-ray reflections on the multi-component solid forms were collected on a Bruker SMART APEX CCD diffractometer equipped with a graphite monochromator and a Mo-Kα finefocus sealed tube (λ = 0.71073 Å) operated at 1500 W power (40 kV, 30 mA).…”

Modification of Physicochemical Properties of Active Pharmaceutical Ingredient by Pharmaceutical Co-Crystals

“…Fael H et al have prepared co-crystal of norfloxacin-based solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, whereas the co-crystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher [74]. Machado Cruz et al develop a new co-crystal of the poorly water-soluble antifungal agent itraconazole.…”

Impact of L-Pyroglutamic Acid on the Solubility of Puerarin: Preparation, Solid-State Characterization and Physicochemical Evaluation of Puerarin-L-Pyroglutamic Acid Co-Crystal

“…Co-crystal is a solids-state form of crystalline single-stage materials made of at least two or more different molecular or ionic compounds commonly in a stoichiometric proportion that are neither solvated nor simple salts. [3,4] The comprehensive definition of co-crystals consists of two or more components that form a unique crystalline form structure, which has extraordinary properties. The design and synthesis of Crystal engineering is the plan and combination of solid-state structures, because of the agreement and utilization of intermolecular interaction, with required properties.…”