With the deepening of drug delivery system research and stricter requirements, new pharmaceutical excipients are emerging, among which hydroxypropyl methylcellulose is widely used. This paper reviews the domestic and foreign applications of hydroxypropyl methylcellulose. The production method and its advantages and disadvantages, equipment technology and domestic improvement prospects, and its application in the field of pharmaceutical excipients.
Key words: pharmaceutical excipients; hydroxypropyl methylcellulose; production; application
1 Introduction
Pharmaceutical excipients refers to the general term for all other medicinal materials added to the preparation except the main drug in order to solve the formability, availability and safety of the preparation in the process of producing and designing the preparation. Pharmaceutical excipients are very important in pharmaceutical preparations. There are many kinds of pharmaceutical excipients in domestic and foreign preparations, but in recent years, the requirements for the purity, dissolution, stability, bioavailability in vivo, improvement of therapeutic effect and reduction of side effects of drugs are getting higher and higher. , making the rapid emergence of new excipients and research processes in order to improve the efficiency of drug preparation and the quality of use. A large number of example data show that hydroxypropyl methylcellulose can meet the above requirements as a high-quality pharmaceutical excipient. The current situation of foreign research and production and its application in the field of pharmaceutical preparations are further summarized.
2 Overview of the properties of HPMC
HPMC is a white or slightly yellow, odorless, odorless, non-toxic powder obtained by etherification of alkali cellulose, propylene oxide and alkyl chloride. Easily soluble in water below 60°C and 70% ethanol and acetone , isoacetone, and dichloromethane mixed solvent; HPMC has strong stability, mainly manifested: first, its aqueous solution has no charge and does not react with metal salts or ionic organic compounds; second, it is also resistant to acids or bases. Relatively stable. It is the stability characteristics of HPMC that make the quality of medicines with HPMC as excipients more stable than those with traditional excipients. In the toxicology study of HPMC as excipients, it is shown that HPMC will not be metabolized in the body, and does not participate in the human body’s metabolism. Energy supply, no toxic and side effects for drugs, safe pharmaceutical excipients.
3 Research on domestic and foreign production of HPMC
3.1 Overview of the production technology of HPMC at home and abroad
In order to better cope with the ever-expanding and increasing requirements of pharmaceutical preparations at home and abroad, the production technology and process of HPMC are also constantly developing on a tortuous and long road. The production process of HPMC can be divided into batch method and continuous method. Main categories. The continuous process is generally used abroad, while the batch process is mostly used in China. The preparation of HPMC includes the steps of alkali cellulose preparation, etherification reaction, refining treatment, and finished product treatment. Among them, there are two types of process routes for etherification reaction. : Gas phase method and liquid phase method. Relatively speaking, the gas phase method has the advantages of large production capacity, low reaction temperature, short reaction time, and precise reaction control, but the reaction pressure is large, the investment is large, and once a problem occurs, it is easy to cause major accidents. The liquid phase method generally has the advantages of low reaction pressure, low risk, low investment cost, easy quality control, and easy replacement of varieties; but at the same time, the reactor required by the liquid phase method cannot be too large, which also limits the reaction capacity. Compared with the gas phase method, the reaction time is long, the production capacity is small, the required equipment is many, the operation is complex, and the automation control and accuracy are lower than the gas phase method. At present, developed countries such as Europe and the United States mainly use the gas phase method. There are high requirements in terms of technology and investment. Judging from the actual situation in our country, the liquid phase process is more common. However, there are many areas in China who continue to reform and innovate technologies, learn from foreign advanced levels, and embark on semi-continuous processes. Or the road of introducing foreign gas-phase method.
3.2 Production technology improvement of domestic HPMC
HPMC in my country has huge development potential. Under such favorable opportunities, it is the goal of every researcher to continuously improve the production technology of HPMC and reduce the gap between the domestic HPMC industry and foreign advanced countries. The HPMC process Every link in the synthesis process is of great significance to the final product, among which the alkalization and etherification reactions [6] are the most important. Therefore, the existing domestic HPMC production technology can be carried out from these two directions. Transformation. First of all, the preparation of alkali cellulose should be carried out at low temperature. If a low-viscosity product is prepared, some oxidants can be added; if a high-viscosity product is prepared, an inert gas protection method can be used. Secondly, the etherification reaction is carried out at high temperature. Put toluene in the etherification equipment in advance, send the alkali cellulose into the equipment with a pump, and add a certain amount of isopropanol according to the needs. Reduce the solid-liquid ratio. And use a computer control system, which can quickly feedback temperature, Process parameters such as pressure and pH are automatically adjusted. Of course, the improvement of HPMC production technology can also be improved from the process route, raw material use, refining treatment and other aspects.
4 Application of HPMC in the field of medicine
4.1 Use of HPMC in the preparation of sustained-release tablets
In recent years, with the continuous deepening of drug delivery system research, the development of high-viscosity HPMC in the application of sustained-release preparations has attracted much attention, and the sustained-release effect is good. In comparison, there is still a big gap in the application of sustained-release matrix tablets. For example, when comparing domestic and foreign HPMC for nifedipine sustained-release tablets and as a matrix for propranolol hydrochloride sustained-release matrix tablets, it is found that the The use of domestic HPMC in sustained-release preparations requires further improvement to continuously improve the level of domestic preparations.
4.2 Application of HPMC in thickening of medical lubricants
Due to the needs of inspection or treatment of some medical devices today, when entering or leaving human organs and tissues, the surface of the device must have certain lubricating properties, and HPMC has certain lubricating properties. Compared with other oil lubricants, HPMC can be used as a medical lubricating material , which can not only reduce the wear of equipment, but also meet the needs of medical lubrication and reduce costs.
4.3 Application of HPMC as natural antioxidant water-soluble packaging film and film coating material and film-forming material
Compared with other traditional coated tablet materials, HPMC has obvious advantages in terms of hardness, friability and moisture absorption. HPMC of different viscosity grades can be used as water-soluble packaging for tablets and pills. It can also be used as a packaging film for organic solvent systems. It can be said that HPMC is the most widely used film coating material in my country. In addition, HPMC can also be used as a film-forming material in the film agent, and the anti-oxidative water-soluble packaging film based on HPMC is widely used in the preservation of food, especially fruit.
4.4 Application of HPMC as a capsule shell material
HPMC can also be used as a material for preparing capsule shells. The advantages of HPMC capsules are that they overcome the cross-linking effect of gelatin capsules, have good compatibility with drugs, have high stability, can adjust and control the release behavior of drugs, improve drug quality, It has the advantages of stable drug release process. Functionally, HPMC capsules can completely replace the existing gelatin capsules, representing the future development direction of hard capsules.
4.5 Application of HPMC as suspending agent
HPMC is used as a suspending agent, and its suspending effect is good. And experiments show that using other common polymer materials as a suspending agent to prepare a dry suspension is compared with HPMC as a suspending agent to prepare a dry suspension. The dry suspension is easy to prepare and has good stability, and the formed suspension meets the requirements of various quality indicators of the dry suspension. Therefore, HPMC is often used as a suspending agent for ophthalmic preparations.
4.6 Application of HPMC as blocker, slow-release agent and porogen
HPMC can be used as blocking agent, sustained-release agent and pore-forming agent to delay and control drug release. Nowadays, HPMC is also widely used in sustained-release preparations and compound preparations of traditional Chinese medicines, such as in Tianshan Snow Lotus sustained-release matrix tablets. Application, its sustained release effect is good, and the preparation process is simple and stable.
4.7 Application of HPMC as thickener and colloid protective glue
HPMC can be used as a thickener [9] to form protective colloids, and relevant experimental studies have shown that using HPMC as a thickener can enhance the stability of medicinal activated carbon. For example, it is commonly used in the preparation of pH-sensitive levofloxacin hydrochloride ophthalmic ready-to-use gel. HPMC is used as thickener.
4.8 Application of HPMC as bioadhesive
The adhesives used in bioadhesion technology are macromolecular compounds with bioadhesive properties. By adhering to the gastrointestinal mucosa, oral mucosa and other parts, the continuity and tightness of the contact between the drug and the mucosa are strengthened to achieve better therapeutic effects. . A large number of application examples show that HPMC can well meet the above requirements as a bioadhesive.
In addition, HPMC can also be used as a precipitation inhibitor for topical gels and self-microemulsifying systems, and in the PVC industry, HPMC can be used as a dispersion protectant in VCM polymerization.
5 Conclusion
In a word, HPMC has been widely used in pharmaceutical preparations and other aspects due to its unique physicochemical and biological properties. Even so, HPMC still has many problems in pharmaceutical preparations. What is the specific role of HPMC in application; how to determine whether it has a pharmacological effect; what characteristics does it have in its release mechanism, etc. It can be seen that while HPMC is widely used, more problems need to be solved urgently . And more and more researchers are doing a lot of work for the better application of HPMC in medicine, thus continuously promoting the development of HPMC in the field of pharmaceutical excipients.
Post time: Nov-02-2022