Views: 7 Author: Site Editor Publish Time: 2023-04-14 Origin: Site
Abstract: Hydroxypropylmethylcellulose (HPMC) is used as the mother material. Using succinic anhydride as esterification agent and anhydrous sodium acetate as catalyst, hydroxypropyl methylcellulose succinate (HPMCS) was prepared by esterification reaction in acetic acid. By changing the reaction temperature, the amount of esterification agent and catalyst, five kinds of hydroxypropyl methylcellulose succinates with different succinyl content were obtained. The content of succinyl group was determined by conductivity titration. The structural characterization and performance tests were carried out by infrared spectroscopy (FI'-IR), viscosity analysis and rheological analysis. The results showed that: the average content (molar ratio) of succinyl groups on each macromolecular chain was 6.57-12.42; The gel temperature of HPMC is 59.85℃; the more succinyl group content and the more uniform distribution, the lower the coagulation cavity temperature, but the greater the gel strength.
Keywords:hydroxypropylmethylcellulose succinate; hydroxypropylmethylcellulose; succinic anhydride; succinyl; gel temperature
In recent years, the thermoreversible gel properties of cellulose derivatives derived from natural resources such as hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) have gradually become a research hotspot. The formation of the gel is mainly due to the association between molecules or segments caused by the hydrophobic group methoxy group in the molecular chain which is very sensitive to temperature, and the existence of hydroxypropyl group has a great influence on the strength of the gel, especially for the gel. The temperature effect is very large. At low temperature, such cellulose derivatives are completely hydrated, and water molecules form an ice-like structure around the hydrophobic group; as the temperature increases, the hydration gradually weakens, thus destroying the ice structure; at the same time , The hydrophobic interaction between polymers is gradually enhanced. Finally, a gel with a three-dimensional cross-linked network structure is formed. The gel temperature can be effectively adjusted by adding some small molecules (salts, alcohols) into the aqueous solution. However, the stability of the gel system formed by this kind of additive mixed system is not good. Therefore, chemical modification of MC, HPMc, etc. has become the most effective way.
hiroyasu% et al carried out the embodiment of the chemical modification of HPMC by trimellitic anhydride. In this paper, succinic anhydride was used to modify HPMC to prepare hydroxypropyl methylcellulose succinate, and the focus was on the effect of succinyl group content on the gel temperature.
1. Experimental part
1.1 Materials and reagents
Hydroxypropyl methylcellulose HPMC (60HD20000), medical food grade, the mass Shu numbers of methoxyl and hydroxypropyloxyl are 28%-30% and 7%-12% respectively; before use, store at 50°C Dry in vacuum for 2h. Succinic anhydride, analytically pure. Anhydrous sodium acetate, glacial acetic acid and 38% hydrochloric acid were all analytically pure. Deionized water was used without further purification.
1.2 Preparation of hydroxypropylmethylcellulose succinate (HPMC)
In a dry round-bottom flask equipped with a reflux tube, add 80 mL of glacial acetic acid and pre-dried 2.59 HPMC, control the temperature at 70 ° C, and stir for about 1 h. After heating to the desired temperature, add 2.59 succinic anhydride and 1.259 anhydrous sodium acetate. After incubation for 5 hours, terminate the reaction with 30 mL of deionized water, then add 3 mL of concentrated hydrochloric acid, and shake well. Slowly pour the reactant into excess 600C deionized water while stirring mechanically to obtain a white flocculent polymer. Filter and wash with 60°C deionized water until neutral. Vacuum-dry at about 50°C and pulverize to obtain HPMCS.
1.3 Infrared Spectroscopy Determination
Infrared spectrum measurement was completed by Nicolet company MAGNA-IR 550 (series Ⅱ) type Fourier transform infrared spectrometer, KBr pellets, resolution 4cm-1, sampling 32 times.
1.4 Preparation of HPMC and HPMCS solutions
Dissolve the dried sample in a certain amount of water and stir it magnetically for about 1 hour, then place it in a refrigerator at 5°C for more than 1 week. spare.
1.5 Measurement of viscosity
The viscosity of the 0.05% (wt) solution was measured using an Ubbelohde viscometer.
1.6 Determination of succinyl content
DDS-307 conductivity meter (Shanghai, China) was used to measure its content. The mass fraction of the sample solution used was 0.2%, and the NaOH concentration was 0.1mol/L. Definition of succinyl group content: the average number of succinyl groups attached to each macromolecular chain.
1.7 Measurement of condensation temperature of HPMCS
Rheoxplorer 200 rheometer (Sweden) measures the influence of temperature on the shear storage modulus G', and the cone angle and diameter of the cone and plate are 4° and 40mm, respectively. The heating rate is 2°C/min. The range is 30°C to 85°C, and the frequency is 1.0Hz. Drop a small amount of silicone oil around or on the surface of the sample.
2. Results and Discussion
2.1 Structural characterization
In the IR diagram of HPMCS 5, a strong sharp absorption peak appears around 1740cm-1, indicating the presence of carbonyl groups, which can be attributed to the carbonyl stretching vibration of hydroxypropyl methylcellulose succinate; while HPMC, at 1730— At 1715cm-1, there is no characteristic absorption of carbonyl. This indicates that the structure of the prepared product is different from that of HPMC.
Viscosity reflects the size of the gravitational force between molecules. Under the condition that other conditions remain unchanged, the mutual attraction between molecules increases with the increase of polymer molecular weight and the enhancement of polarity. From the data in Table 1, it can be seen that the absolute viscosity and intrinsic viscosity of HPMCS are greater than that of HPMC, which shows that the interaction force between macromolecules in the sample solution obtained from the reaction is stronger. Under the conditions of this experiment, the esterification has little effect on the molecular weight, and the molecular weight of the product ranges from 130,000 to 210,000. It can be seen that the main factor affecting the viscosity change of the product is the content of succinyl group.
2.3 Succinyl content
The conductivity titration curve of HPMC and HPMCS 5 shows the conductivity titration curve of HPMC and HMPCS5, the consumption volume (v) of NaOH corresponding to the stoichiometric point and the content of succinyl group obtained therefrom. It can be seen from the synthesis conditions and tests of HPMCS that the content of succinyl group first increases and then decreases with the increase of NaoH consumption volume, and also increases with the increase of the amount of esterification agent and catalyst and the increase of reaction temperature.
2.4 Gel temperature
The measurement of gel temperature has been debated over the years. Winter et al. believe that the temperature corresponding to the intersection point is the gel temperature; this method is simple and convenient, but this method has a certain dependence on the frequency of measurement. Sarkar regards the humidity corresponding to the minimum value of G’ on the G’-T(°C) curve as the gel temperature; but when the scanning temperature exceeds the gel temperature, c’ should show a trend of rapid increase. For the cellulose derivatives herein, neither of these two methods is suitable. In contrast, regional median values are more suitable.
The so-called regional median method: with the increase of the test temperature, the condensation cavity begins near the temperature (t1) corresponding to the first turning point of the storage modulus G'. The gel structure is basically completed around the temperature (t2) corresponding to the second turning point of c'; the average value of the temperatures corresponding to these two turning points is taken as the gel temperature.
It can be seen that: (1) the gel temperature of HPMCS decreases with the increase of succinyl content, and the lowest drops to 41.95°C; (2) the higher the succinyl content, the narrower the temperature range of the gel region, and HPMCS4 is the opposite. in addition. The gel strength tends to increase with the increase of succinyl content and distribution uniformity; the gel strength first increases and then decreases with the increase of catalyst dosage, and decreases with the increase of reaction temperature.
When t<53.7℃, c'decreases slowly with the increase of temperature, showing a typical chain entanglement phenomenon. At 53.7 °C, G' showed the first turning point, indicating that the gel phenomenon began to occur. After crossing the first turning point. c' begins to increase gradually with the increase of temperature. At about 66 °C, G' appeared the second turning point, indicating that the gel network structure was basically completed. The available gel temperature is 59.85°C.
And for HPMCS5. In the initial scanning temperature range, there is no phenomenon that G' decreases with the increase of temperature, and when the scanning temperature is lower than 34.2 °C, G' appears the first turning point, indicating that the gel phenomenon is relatively low. Occurs at low temperature; the second turning point occurs at 49.7°C. The available gel temperature is 41.95°C. In addition, you can also see. When the temperature is lower than 33.3 ℃. The G' value of HPMCS5 is lower than that of HPMC.
In summary, on the one hand, succinyl increases the distance between macromolecules and reduces the chain entanglement between macromolecules, which is why the G' value of HPMCS5 is lower than the c' value of HPMC at lower temperatures s reason. On the other hand, because the carboxyl group is hydrophilic, it can undergo strong hydration with water molecules. The water molecules in the hydration layer around the hydrophobic groups of the cellulose ether molecules are consumed, resulting in the weakening of the hydrogen bond between the macromolecules and the water molecules and the increase of the physical cross-linking points that can be formed, and this trend will increase with Ding The increase of diacyl content was more obvious. Therefore, when the temperature rises, hydrogen bonding and hydrophobic interactions can reach equilibrium at lower temperatures, that is, hydrophobic associations occur; and gelation can occur at lower temperatures as the content of succinyl groups increases. In addition, the more uniform the distribution of succinyl groups, the lower the temperature at which the association occurs, that is, the lower the gel temperature. The reason for the wide temperature range in the area.
According to Sarkar's research results, the gel strength of the sample is related to the density of cross-linking points. For the target product in this paper, the density of crosslinking points is related to the content of T-acyl group and its distribution uniformity. The higher the succinyl content, the better the homogeneity, the higher the density of cross-linking points, and the stronger the gel strength of the resulting sample.
For the adjustment of the gel temperature of hydroxypropyl methylcellulose, chemical methods and methods of adding small molecules can be used. Chemical methods change the microstructure of the original macromolecules, thereby changing the gelation of hydroxypropyl methylcellulose. However, the addition of small organic molecules does not change the microstructure of the original macromolecules, and therefore does not change its gel mechanism, but it can promote gelation to occur at lower or higher temperatures, but it is easy to cause solution Inhomogeneous mixing during the heating process leads to poor gel performance, and the influence of the concentration on the gel temperature is opposite.
To sum up. The higher the succinyl content and the more uniform the distribution, the lower the gelation temperature and the greater the gel strength of HPMCS; the succinyl content increases with the increase of the reaction temperature and the increase of the amount of esterification agent and catalyst Properly increasing the dosage of catalyst anhydrous sodium acetate in the process of esterification and moderate reaction temperature can obtain a gel with lower gel temperature and greater gel strength.