Evaluation Of Effects Of Different Drying Processes And Excipients On Hygroscopicity Of Scutellariae Radix And Coptidis Rhizoma Extracts Based On Physical Fingerprint Spectrum Ⅱ
Sep 02, 2024
Fig. 3 Load dispersion diagram of PCA model analysis
Fig. 4 Score chart of PCA model analysis
2.2.6 PLS pair of powder H
The 12 physical property parameters were standardized and used as independent variables, and the H of the powder was used as the dependent variable for PLS model analysis. The variable importance for the projection (VIP) of the powdery properties of the extract powder on its hygroscopicity is shown in Figure 5. If the VIP value is greater than 1, the independent variable has a significant impact on the dependent variable. The study found that span, width, SSA, D50, Dc, Da, H and HR have a significant impact on H, which reflects the stability of the material powder. Dc, span and SSA are respectively the accumulation, uniformity, and Surface morphology index. Therefore, in-process production, the hygroscopicity of the extract powder can be improved through parameter indicators such as the stability, uniformity, and surface morphology of the material powder.
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2.3 Study on the influence of excipients on the hygroscopicity of extract powder
The chemical composition of traditional Chinese medicine extract powder is complex, containing many highly hygroscopic ingredients such as sugar and starch. It is highly viscous and easily absorbs moisture, which brings difficulties to the subsequent preparation molding process. It can be extracted by optimizing the drying process. Refining removes ineffective hygroscopic ingredients and adding moisture-proof auxiliary materials to reduce hygroscopicity. The experiment selected 5 common excipients in solid preparations such as lactose, β-cyclodextrin, dextrin, microcrystalline cellulose and pregelatinized starch, and ground and mixed the extract powder and excipients at a ratio of 1:1 to prepare a pharmaceutical excipient mixture. And the method of "name of traditional Chinese medicine-drying method-type of excipients" was used for coding to study its impact on hygroscopicity.
2.3.1 Construction of dynamic two-dimensional characterization technology of hygroscopicity
Time is used as the independent variable to characterize the dynamic moisture absorption process of CMEs under normal temperature and pressure, and then the moisture absorption rate-time curve is fitted with a mathematical model to derive parameters representing the characteristics of the curve. From the moisture absorption amount and moisture absorption speed 2 Two perspectives simultaneously describe the dynamic moisture absorption process, forming a two-dimensional classification system [17]. Research shows that CMEs conform to the double-exponential model and the first-order kinetic model [18]. The first-order kinetic model was chosen for experiment fitting to obtain the equilibrium moisture absorption rate (F∞), half-equilibrium moisture absorption time (t1/2), and first-order kinetic constants. (k) and the initial moisture absorption rate (K0), comprehensively describing the entire dynamic moisture absorption process. The first-order kinetic model and Taylor expansion are shown in formulas (11) and (12) respectively, and the relationship between indicators is shown in formulas (13) and (14).
Ft＝F∞(1－e−kt) (11)
Ft＝F∞[kt－2!/(kt)2+3!/(kt)
3－…＋(−n)!/(−kt)(n 12)
K0=F∞k (13)
T1/2＝ln2/k (14)
Among them, F∞ represents the equilibrium moisture absorption rate of CMEs, which reflects the total amount of moisture absorption. The smaller t1/2 is, the faster the CMEs reach equilibrium, and it is also an indicator of the strength of hygroscopicity. Therefore, F∞ and t1/2 are combined with the two angles of total moisture absorption and moisture absorption speed to jointly reflect the strength of hygroscopicity. F∞ and t1/2 are combined to construct a two-dimensional coordinate system. According to the characteristics of hygroscopicity of CMEs, F∞ is selected =15%, 1/t1/2=0.05 h−1 is the coordinate center, and the powders are divided into 4 categories according to their hygroscopic behavior: ① Large equilibrium moisture absorption capacity and fast moisture absorption speed; ② Large equilibrium moisture absorption capacity and slow moisture absorption speed; ③ The balance moisture absorption capacity is small and the moisture absorption speed is slow; ④The balance moisture absorption capacity is small and the moisture absorption speed is fast.
Fig. 6 Hygroscopic curves of samples of Scutellariae Radix with different drying methods and medicine-comixture
Fig. 7 Hygroscopic curves of Coptidis Rhizoma samples with different drying methods and medicine-comixture
2.3.3 Two-dimensional characterization results of hygroscopicity of CMEs and drug-excipient mixtures
The first-order kinetic model was used to fit the hygroscopic curves of each CME and its mixtures with different excipients, and the analysis was performed according to the established two-dimensional characterization method. The study found that the samples of the three drying methods of the scutellaria extract powder measured belonged to the second category, with large equilibrium moisture absorption and slow moisture absorption rate. Most of the drug-excipient mixtures belonged to the third category, with different F∞ and t1/2, small equilibrium moisture absorption and slow moisture absorption rate. Among them, the equilibrium moisture absorption of the drug-excipient mixture of the scutellaria atmospheric pressure dried sample and β-cyclodextrin was the smallest, and the moisture absorption rate of the drug-excipient mixture of the scutellaria vacuum dried sample and β-cyclodextrin was the smallest. After adding excipients, its hygroscopicity was improved;
The atmospheric pressure and spray extract powders of Coptis chinensis belonged to the second category, and its drug-excipient mixtures all belonged to the third category. Among them, the drug-excipient mixture of the vacuum sample of Coptis chinensis and lactose had the smallest equilibrium moisture absorption, and the drug-excipient mixture of the vacuum sample of Coptis chinensis and β-cyclodextrin had the smallest moisture absorption rate. The results are shown in Figure 8. β-cyclodextrin has obvious advantages in reducing the equilibrium moisture absorption of Coptis chinensis and Scutellaria baicalensis and reducing their moisture absorption rate. Because of the existence of the cavity structure, the auxiliary materials and the extract powder are fully ground and mixed, and part of the extract powder enters the cavity, forming surface-wrapped particles, which makes the particles (D50) larger, the particle gap ratio (Ie) decreases, and the SSA with air decreases, thereby reducing the hygroscopicity of the material. The secondary index determination of the drug-excipient mixture also further confirms it. Lactose can significantly reduce the equilibrium moisture absorption of vacuum-dried Coptis chinensis extract powder, which may be because it itself has no hygroscopicity. When it is ground with the extract powder, fine auxiliary material particles will adhere to the surface of the extract, reducing the contact area with the environment and reducing the equilibrium moisture absorption.
2.3.3 Two-dimensional characterization results of hygroscopicity of CMEs and drug-excipient mixtures
The first-order kinetic model was used to fit the hygroscopic curves of each CME and its mixtures with different excipients, and the analysis was performed according to the established two-dimensional characterization method. The study found that the samples of the three drying methods of the Scutellaria extract powder measured belonged to the second category, with large equilibrium moisture absorption and slow moisture absorption rate. Most of the drug-excipient mixtures belonged to the third category, with different F∞ and t1/2, small equilibrium moisture absorption, and slow moisture absorption rate. Among them, the equilibrium moisture absorption of the drug-excipient mixture of the Scutellaria atmospheric pressure dried sample and β-cyclodextrin was the smallest, and the moisture absorption rate of the drug-excipient mixture of the Scutellaria vacuum dried sample and β-cyclodextrin was the smallest. After adding excipients, its hygroscopicity was improved;
The atmospheric pressure and spray extract powders of Coptis chinensis belonged to the second category, and its drug-excipient mixtures all belonged to the third category. Among them, the drug-excipient mixture of the vacuum sample of Coptis chinensis and lactose had the smallest equilibrium moisture absorption, and the drug-excipient mixture of the vacuum sample of Coptis chinensis and β-cyclodextrin had the smallest moisture absorption rate. The results are shown in Figure 8. β-cyclodextrin has obvious advantages in reducing the equilibrium moisture absorption of Coptis chinensis and Scutellaria baicalensis and reducing their moisture absorption rate. Due to the presence of a cavity structure, the excipients and extract powder are fully ground and mixed, and part of the extract powder enters the cavity, forming surface-coated particles, which makes the particles (D50) larger, the particle gap ratio (Ie) decreases, and the SSA with air decreases, thereby reducing the hygroscopicity of the material. The secondary index determination of the drug-excipient mixture also further confirms this. Lactose can significantly reduce the equilibrium moisture absorption of vacuum-dried Coptis chinensis extract powder. It may be because it itself has no hygroscopicity. When it is co-grinded with the extract powder, fine excipient particles will adhere to the surface of the extract, reducing the contact area with the environment and reducing the equilibrium moisture absorption.
3 Discussion
The technology for improving the hygroscopicity of Chinese medicine extracts is divided into excipient modification and process modification. Different drying methods belong to process modification, and the use of weakly hygroscopic excipients for mixing or drug-excipient co-grinding, particle coating, granulation, encapsulation and coating are excipient modifications [19]. In this experiment, the extract powders obtained by different drying methods of Scutellaria baicalensis and Coptis chinensis were used as the research objects. The physical fingerprints and similarity matrices of each sample were established with 12 physical parameters corresponding to 5 primary indicators to evaluate the differences in the effects of different drying methods on the powder.
The stacking and stability of the extract powders dried at normal pressure and vacuum were good, which may be because they underwent crushing and sieving after drying. The secondary indicators Da and Dc related to density became larger in the preparation process, which reduced the contact area with the external environment, thereby reducing the moisture absorption and improving its stability. The uniformity and compressibility of the spray-dried extract powder were relatively ideal. The spray drying process atomized the Chinese medicine extract into extremely fine droplets, and at the same time, it was dried at high temperatures instantly. The particle size of the obtained extract powder was small and uniform. The secondary indicators of the compressibility of the extract powder had large porosity and specific surface area, which was conducive to the subsequent granulation, tableting and other preparation processes. At the same time, this also led to obvious moisture absorption of the extract powder and decreased stability. The fluidity indexes were all less than 5, and the secondary index repose angles were all >40°, and the fluidity was poor. Studies have shown that the particle size of powder is the most important factor in determining its powder properties. The adsorption, solubility, fluidity, uniformity and compressibility of Chinese medicine extract powder will change accordingly[20]. The HR and H values representing the stability of the three drying methods are all large, and the hygroscopicity is strong. The hygroscopic mechanism may be related to the chemical composition or crystal transformation of the Chinese medicine extract powder[21].
The experiment found that the fluidity and stability of Scutellaria baicalensis extract powder were slightly worse than those of Coptis chinensis. The main difference between the two was that the moisture absorption of Scutellaria baicalensis extract powder was more obvious during the storage process, and the tendency of agglomeration and dissolution was serious. The physical fingerprint spectrum found that the similarity of Scutellaria baicalensis samples dried at normal pressure was not high, while the similarity of vacuum and spray drying was higher, while the similarity of Coptis chinensis samples dried at normal pressure, vacuum and spray drying was higher. This may be due to the differences in the physical and chemical properties of Scutellaria baicalensis and Coptis chinensis. The main chemical components of Scutellaria baicalensis are flavonoids, terpenoid compounds and polysaccharides. The extract powder was dried and crushed, resulting in powder indicators such as SSA and span lignans. The hygroscopicity of the main components was slightly better than that of Scutellaria baicalensis. The results of the secondary powder indicators D50, IC, Ie and SSA also verified that the Coptis chinensis extract powder was stable and uniform, with a slightly better moisture-proof effect. The preparation process did not destroy the structural stability, and the physical fingerprints of each process were highly similar [22]. The hygroscopicity of CMEs and drug-excipient mixtures was characterized according to the established two-dimensional characterization method. Each CME and drug-excipient mixture was classified according to its hygroscopic behavior. Most of the extract powders of Scutellaria baicalensis and Coptis chinensis belonged to the second category, with large equilibrium hygroscopic capacity and slow hygroscopic rate. After adding excipients and grinding and mixing, most of the drug-excipient mixtures belonged to the third category, with small equilibrium hygroscopic capacity and slow hygroscopic rate. β-cyclodextrin and lactose had the most significant effects. The addition of various moisture-proof excipients would change the contact area between the extract powder particles and the external environment to varying degrees, reducing water absorption. The key powder physical properties of CMEs and mixed powders with excipients, such as particle size, porosity, and specific surface area, are the key factors affecting F∞ and t1/2, and are correlated with the dynamic two-dimensional characterization parameters of hygroscopicity[23]. PCA model analysis found that the contributions to principal component 1 were greater for IH, HR, H, Da, Dc and particle size D50. The clustering part also showed a strong correlation between each other, which was highly correlated with the stability, stacking and uniformity of the powder material. In the production process of solid preparations, reducing the equilibrium moisture absorption of materials and controlling the moisture absorption rate are one of the keys to ensure the quality of preparations. Specific excipients can be screened according to the moisture absorption behavior classification to effectively prevent the moisture absorption phenomenon of traditional Chinese medicine preparations.
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