Views: 1 Author: Site Editor Publish Time: 2023-05-24 Origin: Site
Abstract: Hydroxypropyl methylcellulose is a non-toxic, odorless, white or Class white powder. In the pharmaceutical industry, it is mainly used as a rate-controlling polymer material for coating materials, film materials, and sustained-release preparations. It can also be used as a stabilizer, suspending agent, tablet adhesive, and viscosifier. It can also be used in the construction industry and coatings. industry and other fields.
Key words: hydroxypropyl methylcellulose; medicine; progress
Hydroxypropyl methylcellulose (hydroxypropyl methylcellulose, HPMC), also known as hypromellose or cellulose hydroxypropyl methyl ether, is made of highly pure cotton cellulose through special etherification under alkaline conditions. have to. HPMC can be used as a high-quality pharmaceutical excipient and is widely used in the field of modern medicine. First, when hypromellose is used as a binder or disintegrant, it can significantly improve the solubility of the tablet; secondly, HPMC can also be used as a coating film-forming material to improve the stability of the drug; in addition, when HPMC is used as a sustained-release Or controlled-release matrix materials can finally achieve the purpose of sustained and controlled release of drugs by blocking or controlling the release of drugs, which is of great benefit to some clinical diseases. When HPMC is used as a capsule material for medicine, its stability and drug disintegration and dissolution are obviously superior to other traditional capsule materials such as gelatin capsule materials; when it is used as a suspending agent, it can increase the suspending liquid The stability of the preparation.
2. Physicochemical properties and other characteristics of hydroxypropyl methylcellulose
2 . 1 Physicochemical properties of hydroxypropyl methylcellulose
The appearance of HPMC is white or off-white powder, the relative molecular mass is about 86000, and it is made by etherification of alkali cellulose, propylene oxide and alkyl chloride. The particle size is generally 100 mesh, the pass rate is greater than 98.5%, and the 80 mesh pass rate is 100%. There are also special specifications with a particle size of 40-60 mesh. HPMC is non-toxic, odorless, and resistant to heat, light, and humidity. Strong stability, easily soluble in water, soluble in some solvents, such as ethanol/water solution with proper ratio. Its aqueous solution has surface activity and high transparency, and the products of different specifications have different gel temperatures. The solubility of HPMC generally changes with the viscosity, and the lower the viscosity, the greater the solubility. There are also certain differences in the performance of different specifications of HPMC, and the solubility in water is not affected by the pH value. HPMC is a non-ionic cellulose ether, which is chemically inert and does not interact with other ions or salts. Therefore, when HPMC is applied in the field of medicine, it will not react with other excipients and affect the properties of the substance itself. HPMC does not react with other raw materials and auxiliary materials because of its inertness in the production process of the preparation. At the same time, it has relatively strong anti-allergic properties. With the increase of the degree of substitution inside the molecular structure, the anti-allergy becomes stronger and more stable, which is beneficial to improve the preparation. production efficiency.
2 . 2 Other properties of hydroxypropyl methylcellulose
HPMC is relatively stable to acid or alkali, HPMC aqueous solution can provide strong surface activity, and it has efficient emulsification in two-phase system, so it can be used as a stabilizer in the pharmaceutical field; HPMC aqueous solution has good film-forming properties , Can be applied to tablets or pills as a coating material. Combination of HPMC and glycerol can improve plasticity. In addition, in the toxicity study of HPMC as an excipient, the half-lethal dose response to rats and mice shows that HPMC will not be metabolized in the human body, does not participate in the energy supply of the human body, and is non-toxic and irritating. Drugs have no side effects.
3. Application of hydroxypropyl methylcellulose in the field of medicine
3. 1 Application of hydroxypropyl methylcellulose as binder or disintegrant
When HPMC is used as a binder, it can effectively reduce the contact angle with the drug, make the drug easy to wet when used, and expand several times through its own water absorption properties, significantly improving the dissolution rate of the tablet; and according to the strong viscosity of HPMC It is applied to raw materials such as loose texture, and improves the compressibility of drugs by enhancing the viscosity of granules. High-viscosity HPMC is only used as a binder. According to reports, in the production process of ibuprofen tablets, the use of ethanol solution of HPMC as a binder for granulation can significantly improve the dissolution rate of ibuprofen. The low-viscosity HPMC can be directly used as a disintegrant for tablets, pills, etc. When the temperature is constant, under the same inherent viscosity of HPMC, the viscosity of the solution will increase with the increase of the concentration, thereby increasing the hardness and prolonging the disintegration time. In actual production, if the concentration of HPMC solution is too low, the hardness of the obtained particles is small, the disintegration is fast, and cracks are more likely to occur. In order to avoid the occurrence of the above situation, the intrinsic viscosity of HPMC should be measured, and the effect should be judged according to the hardness and disintegration time after tableting, so as to provide a theoretical basis for the application of HPMC with different intrinsic viscosities in production.
3. 2 Application of hydroxypropyl methylcellulose as coating film-forming material
The application of HPMC as a coating film-forming material is due to its good film-forming properties. HPMC can form a transparent and tough film, and it is not prone to adhesion during production. For unstable drugs such as easy to absorb moisture, using HPMC to form a film can improve the stability of the drug. Relevant experiments show that choosing a certain concentration of HPMC as a film-forming agent can reduce the internal stress of the film and ensure that the coated tablet will not appear "orange peel" or "crack"; for engraved drugs, it can also ensure that the edge of the word No leaks. Shan Yuhua once reported that 2% HPMC alcohol solution was used instead of gelatin as the isolation layer to improve the stability and dissolution rate of aspirin enteric-coated tablets. In addition, the application of HPMC in drug film formation can also ensure that the drug will not be denatured for a long storage period, which is better than gelatin film-forming drugs.
3. 3 Application of hydroxypropyl methylcellulose as a matrix material for sustained or controlled release
Sustained-release preparations refer to preparations that can be continuously released for a long time after medication to achieve long-acting effects. Controlled-release preparations refer to drugs that are automatically released in the body at a predetermined speed within a specific period of time, allowing the blood drug concentration to remain stable for a long time. A preparation that is kept constant within the effective concentration range. Sustained-release or controlled-release preparations are the third generation of pharmaceutical preparations, and they are also widely used dosage forms in the field of medicine. At present, HPMC is used as the skeleton material, and the sustained-release tablets can be prepared according to the different viscosity of HPMC to coordinate the dissolution behavior of the preparation. During the screening of the prescription, it was found that when the dosage of HPMC exceeds 20%, it can show a good sustained-release effect, and the dosage is similar to that of The sustained-release effect is directly proportional to the release rate and inversely proportional to it.
3. 4 Application of hydroxypropyl methylcellulose as capsule material
The capsule shell of traditional capsules mostly uses gelatin. The production process of gelatin as the capsule shell is simple, and it has poor protection against sensitive drugs such as moisture and oxygen. In the process of storage, there will be delays in disintegration, which seriously affects the properties of the drug. Zhang Cunyan and others studied that HPMC can effectively improve the release behavior of drugs through the interaction with different excipients, and can overcome the defects of gelatin as capsule material. By optimizing the prescription and process of the corresponding capsule drug, HPMC can also regulate the release behavior of the drug to optimize the quality of the drug and stabilize the drug release process.
3. 5 Application of hydroxypropyl methylcellulose as suspending agent
Suspending agent refers to an additive that can increase the viscosity of the dispersion medium and achieve the purpose of reducing the sedimentation velocity of the particles or increasing the hydrophilicity of the particles. The colloidal solution of HPMC can effectively reduce the tension of the solid-liquid medium interface, reduce the surface free energy of particles, and stabilize the heterogeneous dispersion system. It can be used as an excellent suspending agent in the field of medicine. Relevant test results show that when HPMC is used as a suspending agent, it can quickly dissolve in the body, and its redispersion performance is good. At the same time, repeated tests show that the stability of the optimal formulation of HPMC is feasible. Taking the preparation of calamine lotion with HPMC as an example, the prepared lotion shows loose solid particles and uniform and fine texture, and the sediment can be redispersed by shaking, with good stability.
3. 6 Application of hydroxypropyl methylcellulose as an auxiliary material for oral preparations
HPMC can be used in combination with polyvinyl alcohol and propylene glycol as a film-forming material for oral preparations. The experimental research results of Wang Tongshun and others on the compound licorice zinc amlexanox film suggest that licorice zinc and amlexanox can penetrate into the skin very well and play a role on the ulcer surface, which can promote the healing of the ulcer surface faster and better. heal. The experimental data of Fu Xudong et al. prepared amlexanox buccal tablets with carbomer and HPMC as adhesive materials showed that when the mass ratio of the two was 1:3, the buccal tablets had better taste, smooth surface, simple and feasible process, and easy Realize mass production, controllable quality, increase the residence time of drugs in the lesion, and improve patient compliance.
3. 7 Application of hydroxypropyl methylcellulose as gel matrix
In recent years, gels have received widespread attention and are often used in eye, nasal and skin system drug delivery. In the comparative study of Fukang gel molding process, the finished product is not delicate enough with carboxymethyl cellulose sodium as the matrix, and the drug extract is unevenly distributed in it with carbomer as the matrix, and the preparation process is cumbersome. As the matrix, there will be stratification after placement, so using HPMC as the matrix can improve the above shortcomings. HPMC is used as the main matrix to prepare Qingkailing ophthalmic gel, which has the advantages of simple operation, high production efficiency, good formability, good clarity, low cost and controllable quality.
With the continuous advancement of modern medical technology, the formulation of pharmaceutical preparations is in the process of continuous optimization, and the selection of appropriate excipients has a greater impact on the preparation efficiency of drugs and the quality of drugs used. According to the physical and chemical properties of HPMC, the choice of viscosity of HPMC determines the application direction of HPMC, and HPMC with different viscosities can be used in different pharmaceutical dosage forms. Scholars at home and abroad are also gradually deepening the research on the drug release mechanism and internal structure of hypromellose, the study of the structure-activity relationship of hypromellose; how to accurately quantify and control the impurities contained; the batch-to-batch differences and Quality stability issues and so on. Only by fully understanding its performance and controlling its quality, can hypromellose be better applied in the research of new dosage forms and new drug delivery systems, and promote the continuous development of pharmaceutical formulations.