Hydroxypropyl methylcellulose (HPMC) is a nonionic cellulose alkyl hydroxyalkyl mixed ether obtained by alkalization, etherification, neutralization, and washing of cellulose.
As a nonionic cellulose mixed ether with excellent performance, HPMC has good dispersing, emulsifying, thickening, bonding, water retention, and glue retention properties like other cellulose ethers such as CMC, MC, HEC, CMHEC, HEMC, and HBMC. It is soluble in water and dissolved in ethanol and acetone below 70%. HPMC can be widely used as film coating, sustained release agent, and adhesive for pharmaceutical preparations. Its thickening, dispersing, and emulsifying film-forming properties can also be commonly used in petrochemicals, building materials, ceramics, textiles, food, daily chemicals, synthetic resins, medicine, coatings, and electronics industries.
The etherification reaction of HPMC is a complex yet fascinating process. It involves the replacement of the hydroxyl group (—OH) on cellulose with hydroxypropyl (-OCH₂CHOHCH₃), followed by a continuous chain polymerization with propylene oxide. Theoretically, the hydroxyl group on the hydroxypropyl group on the side chain can continuously react with propylene oxide. However, the reaction is not limited to the hydroxyl group on the glucose ring of cellulose. Methyl chloride can also react with the hydroxyl group on the attached hydroxypropyl group, which terminates the side chain and the hydroxypropylation. This complexity adds to the intrigue of HPMC’s production process.
1. Control of methoxy and hydroxypropyl content of hydroxypropyl methylcellulose
The methoxy and hydroxypropyl content and ratio of HPMC influence the product’s water solubility, water retention capacity, surface activity, and gelation temperature.
HPMC with high methoxy content and low hydroxypropyl content typically has good water solubility, surface activity, and low gelation temperature. However, adjusting the hydroxypropyl content and reducing the methoxy content can increase the gelation temperature. It’s important to note that too high a hydroxypropyl content can reduce the gelation temperature, deteriorate the water solubility and surface activity, and improve the solubility in organic solvents.
The main ways to control and adjust the methoxy and hydroxypropyl content are as follows.
Change the amount of alkali used in the reaction system. The amount of alkali used in the cellulose alkalization process will directly affect the product’s etherification efficiency and group content ratio. The general rule is: high alkali concentration or increased amount of solid alkali added will increase the methoxy content of the product; low alkali concentration or less solid alkali added, under the same process conditions, can appropriately increase the hydroxypropyl content of the product. In other words, the hydroxypropyl content is inversely proportional to the alkali concentration, and the methoxy content is proportional to the alkali concentration.
②Adjust the temperature change of the production process. In the etherification stage of the HPMC production process, the primary reactions are methylation and hydroxypropylation. The reaction conditions required for these two reactions are different, and the positive and negative reaction rates of the two reactions are also quite different. This difference in reaction conditions and the difficulty in coordination makes the HPMC production process control and product structure more complex and unpredictable. Combined with the product index requirements, full consideration of the equipment’s structural characteristics, and quantitative analysis and testing on the basis of a large amount of practice, it is possible to reasonably control the process, adjust the formula, and achieve the desired effect.
Generally speaking, the hydroxypropylation reaction can be carried out at about 30°C, and the reaction rate is greatly accelerated at 50°C; the methylation reaction is slow at 60°C and even weaker at below 50°C. According to the difference in the reaction temperature of the two, a specific temperature is usually controlled to make a particular reaction the primary reaction, such as keeping a constant temperature at 50-60°C for some time, mainly for the hydroxypropylation reaction. Then, the heating rate is controlled to rise to the second etherification reaction stage dominated by the methylation reaction within a certain period, and the reaction time is controlled to achieve a balance between the methoxyl group and the hydroxypropyl group and obtain a product with a reasonable structure. This multi-stage control technology is also conducive to reducing side reactions and post-processing.
The amount of etherifying agent added Under the determined process conditions, the amount of etherifying agents methyl chloride and propylene oxide and the ratio of the two have a direct and noticeable effect on the methoxy and hydroxypropyl values of the product. Constant reaction conditions, unchanged ratio, increasing the content of etherifying agent, improving the content of substituent groups, methoxy, and hydroxypropyl values are constant within a specific range; changing the ratio, increasing the content of one etherifying agent, the corresponding content of substituent groups increases, and the content of the other substituent group decreases.
Our research findings underscore the importance of the amount of methyl chloride and propylene oxide added. They allow us to control the methoxy and hydroxypropyl content of the product within the range of 4% to 12%, providing valuable insights for the production process.
2. Control of viscosity and purity of hydroxypropyl methylcellulose
Depending on the application requirements of the product, HPMC usually has extensive requirements for viscosity and purity.
At the same degree of substitution, viscosity has a particular influence on gel temperature: low viscosity means high gel temperature; high viscosity means low gel temperature. When other indicators are the same, the purity of the product also has a particular influence on the gel temperature. When the salt content is high, the gel temperature of the product will decrease.
Adjusting the purity of HPMC through the washing process is a critical step in the production process. To increase the viscosity, high-polymerization cellulose raw materials can be used, antioxidants can be added, air can be evacuated, and nitrogen can be filled for protection. The viscosity of the product can also be increased by micro-crosslinking the final product. To reduce the viscosity of the product, low-polymerization cellulose raw materials can be used, oxidants can be added during the alkalization process or etherification process, and the viscosity can also be reduced by radiation.
