AAPS PharmSciTech · 2026
Optimizing Particle Size of pH Modifiers Enhances Dissolution of Weakly Basic Drugs.
СтатьяНазвание и аннотация: Перевод в очереди
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Wu Kejia, Feng Yupeng, Zhang Zherui, Jiao Junyao, Zhang Weiwei, Wei Dandan, He Haibing, Zhang Yu, Yin Tian, Bao Zhihong, Wang Yanjiao, Tang Xing
Аннотация
OBJECTIVE: This study aimed to investigate the pH-dependent dissolution of the weakly basic drug carvedilol (BCS Class II) and systematically examine the influence of citric acid concentration and particle size on its release.
METHODS: A series of dissolution studies was conducted in media simulating the gastrointestinal pH range (1.2-7.8), specifically evaluating the effects of citric acid concentration (3% and 9%) and particle size (fine Dv50 44 μm vs. coarse Dv50 608 μm).
RESULTS: Under acidic conditions (pH 1.2-1.6), carvedilol solubility was high and the effect of citric acid particle size was negligible (<1.3% difference). In the mid-pH range (3.8-6.5), fine citric acid particles rapidly created an acidic microenvironment (pH 3.5±0.2), enhancing carvedilol solubility 2.1-2.8-fold and improving dissolution by 3.1-15.7% compared to coarse particles; increasing the citric acid concentration from 3% to 9% reduced this particle size-dependent variability. At high pH (6.8-7.8), the effect of citric acid weakened, though coarse particles still prolonged acid release.
CONCLUSION: While citric acid concentration universally enhanced carvedilol dissolution, the effect of its particle size was pH-dependent, being negligible at low pH but pronounced at higher pH, where larger particles sustained drug release more effectively.
METHODS: A series of dissolution studies was conducted in media simulating the gastrointestinal pH range (1.2-7.8), specifically evaluating the effects of citric acid concentration (3% and 9%) and particle size (fine Dv50 44 μm vs. coarse Dv50 608 μm).
RESULTS: Under acidic conditions (pH 1.2-1.6), carvedilol solubility was high and the effect of citric acid particle size was negligible (<1.3% difference). In the mid-pH range (3.8-6.5), fine citric acid particles rapidly created an acidic microenvironment (pH 3.5±0.2), enhancing carvedilol solubility 2.1-2.8-fold and improving dissolution by 3.1-15.7% compared to coarse particles; increasing the citric acid concentration from 3% to 9% reduced this particle size-dependent variability. At high pH (6.8-7.8), the effect of citric acid weakened, though coarse particles still prolonged acid release.
CONCLUSION: While citric acid concentration universally enhanced carvedilol dissolution, the effect of its particle size was pH-dependent, being negligible at low pH but pronounced at higher pH, where larger particles sustained drug release more effectively.