Industrial Sustainable Decrystallizing Formulation to Enhance Dissolution of Candesartan Cilexetil: Overcoming Limitations of Traditional Solid Dispersion Approaches

工业可持续去结晶制剂提高坎地沙坦酯的溶解度:克服传统固体分散方法的局限性

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Abstract

Background/Objectives: Conventional solid dispersion methods face significant industrial limitations, including thermal degradation, residual organic solvents, and complex preparation processes. This study presents a novel decrystallizing formulation using poloxamer and propylene glycol that remains solid during storage but liquefies at physiological temperature (37 °C). Methods: Decrystallizing formulations containing various poloxamer types (407 and 188) at different concentrations (5-25% w/w) were prepared and assessed for decrystallization temperature, decrystallization time, and drug solubility. The optimal formulation was further characterized using FTIR analysis, as well as in vitro liquefaction performance and dissolution studies. Finally, the industrial sustainability of the decrystallizing formulation was assessed against conventional methods. Results: Poloxamer 407 exhibited higher decrystallization temperature, longer decrystallization time, and superior solubilization capacity compared to Poloxamer 188. Maximum drug solubility (5.51 ± 0.08 mg/g) was achieved at 20% w/w of poloxamer 407 with a decrystallization temperature of 37 °C, and it took 216 s for decrystallization. FTIR spectroscopy confirmed hydrogen bonding interactions, which are responsible for temperature-dependent phase transitions. The decrystallizing formulation showed remarkable improvement in dissolution efficiency (80.6 ± 3.9%) compared to the raw drug (1.8 ± 0.8%), a physical mixture (11.1 ± 6.0%), and a marketed tablet (30.8 ± 2.2%). Conclusions: The current decrystallizing formulation offers a promising approach for improving the bioavailability of poorly water-soluble drugs and tackling the limitations of conventional methods. Moreover, it provides additional advantages in terms of industrial sustainability for continuous production compared to conventional approaches.

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