Effect of precipitation inhibitors on pH-induced supersaturated phase behavior of dl-tetrahydropalmatine
10.7501/j.issn.0253-2670.2020.24.007
- VernacularTitle: 沉淀抑制剂HPMC K4M, HPMC AS MG, Soluplus对pH值诱导延胡索乙素过饱和相行为的影响
- Author:
Hai-Bo DING
1
Author Information
1. Key Laboratory of Modern Preparation of Chinese Meteria Medica, Ministry of Education, Jiangxi University of TCM
- Publication Type:Journal Article
- Keywords:
Dl-tetrahydropalmatine;
HPMC AS MG;
HPMC K4M;
Maximum supersaturation;
PH-shift dissolution;
Phase diagram;
Precipitation inhibitor;
Solubility;
Soluplus;
Supersaturated phase
- From:
Chinese Traditional and Herbal Drugs
2020;51(24):6188-6195
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the effect of three types of precipitation inhibitors (PPI) HPMC K4M, HPMC AS MG and Soluplus on the pH-induced supersaturated phase behavior of dl-tetrahydropalmatine (dl-THP) at oral clinical doses. Methods: dl-THP pH solubility phase diagram and desaturation curve during pH-shift were drawn, and the solubility phase diagram was used to support dl-THP phase behavior. Area under the concentration-time curve and supersaturation ratio were used to analyze the effect of PPI on the phase behavior of dl-THP; Polarized light microscope and differential scanning calorimetry were used to analyze the precipitation properties. Results: Under the clinical dosage, the maximum supersaturation of dl-THP during the pH-shift was 3.93, and the supersaturation was lost over time; HPMC K4M, HPMC AS MG, and Soluplus could all maintain the supersaturation within 180 minutes during the pH-shift dissolution. HPMC K4M, HPMC AS MG, and Soluplus maintained supersaturation levels of 1.19, 1.89 and 1.36 respectively at a concentration of 5%, 1.30, 2.35 and 1.86 at a concentration of 20%, and 1.30, 2.60 and 2.07 at a concentration of 50%. Polarized light microscopy and differential scanning calorimetry results showed that crystalline precipitation occurred. Conclusion: All precipitation inhibitors can improve the pH-induced supersaturated phase behavior of tetrahydropalmatine, and this improvement behavior varies with the type and concentration of precipitation inhibitors. HPMC AS MG has the best effect.
