Effect of external mechanical forces on the crystallographic solid form and dissolution rate of traditional Chinese medicine extracts——taking Ligustrum lucidum extract as an example
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摘要:
以女贞子提取物为例，考察不同制剂工艺条件下机械外力对晶体学固态形式及药物溶出这一关键质量属性的影响，为中药制剂的制备与质量控制提供指导。在不同粉碎和压片工艺条件下，采用偏光显微镜观察女贞子提取物的晶体学固态形式变化。同时，考察该变化对提取物溶出速率的影响，分析晶体含量和溶出速率之间的数学关系。结果显示，球磨及压片工艺对女贞子提取物的晶体学固态形式产生显著影响，无定形态的提取物出现了明显的转晶现象，且转晶后溶出速率显著下降。进一步的研究揭示了晶体含量和溶出速率之间存在负相关的线性关系。研究结果表明，中药提取物在制剂过程中可能会存在晶体学固态形式转变现象，这一现象可能对中药制剂的质量产生潜在风险，提示我们在中药制剂的制备过程中，应重视和加强对中药提取物晶体学固态形式的研究，以保障中药制剂的安全性、有效性与质量可控性。
Abstract:Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.
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Figure 1. HPLC chromatograms of solvent (A), oleanolic acid (B) and Ligustrum lucidum extract (C)
1: Oleanolic acid
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Figure 2. Polarized light microscope(PLM) diagrams of L. lucidum extract with different airflow crushing times
A: Non-airflow crushing; B: Airflow crushing 1 time; C: Airflow crushing 2 times; D: Airflow crushing 3 times
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Figure 3. PLM diagrams of L. lucidum extract after ball milling for different time
A: Non-ball milling; B: Ball milling for 10 min; C: Ball milling for 20 min; D: Ball milling for 30 min
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Figure 4. PLM diagrams of L.lucidum extract under different pressures
A: 75 MPa surface; B: 75 MPa inside; C: 225 MPa surface; D: 225 MPa inside; E: 375 MPa surface; F: 375 MPa inside
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Figure 6. PLM diagrams of L. lucidum extract sample 1–5
A: Sample 1; B: Sample 2; C: Sample 3; D: Sample 4; E: Sample 5
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Figure 7. Intrinsic dissolution profiles of L.lucidum extract sample 1−5 ($\bar{x}\pm {{s}} $, n=3)
Table 1 Intrinsic dissolution rate(IDR) of L.lucidum extract samples 1−5
Sample IDR equation r2 IDR/(mg·cm−2·h−1) Sample 1 Y= 1.3878 X−1.5143 0.9903 1.3878 Sample 2 Y= 0.9259 X−1.0000 0.9970 0.9259 Sample 3 Y= 0.6226 X−0.6791 0.9973 0.6226 Sample 4 Y= 0.4027 X−0.4603 0.9595 0.4027 Sample 5 Y= 0.0197 X+0.1879 0.9831 0.0197 
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