Hydroxypropyl methyl cellulose (HPMC) is a white or nearly white fibrous powder or particle. It has excellent cold water solubility and, as it is a non-ionic cellulose ether, it does not carry a charge in the aqueous solution, thus having strong stability and good compatibility with other excipients or API. Toxicological research data indicates that it is not metabolized in the body and has no toxic side effects, making it a safer pharmaceutical excipient. Due to the differences in its molecular weight and viscosity, it possesses properties such as adhesion, thickening, suspension aid, emulsification, and film formation. Therefore, it is widely used in formulations and is commonly employed as a binder, dispersant, thickener, film coating material, sustained-release matrix material, etc. in pharmaceutical preparations. Now, let's briefly introduce these applications.
1) As a binder and disintegrant in tablets
The currently available HPMC products are mostly from Dow Chemical Company. HPMC can be classified into E/K/F series based on the difference of methoxy and hydroxypropyl methyl groups. Each series can be further divided into different types according to the viscosity. Among them, the E3/E5/E6/E15/E50 series can be used as a binder in tablet formulations, while the E series, including E4M/E10M, is generally used as a film-forming material for coating; the K series, such as K100LV/K15M/K100M, is mostly used as a sustained-release matrix material. The HPMC used as a binder is the low-viscosity specification E3-E50 series. The commonly used concentration of 2-5% HPMC solution is used as a binder. The low-viscosity HPMC dissolves in water solution to form a clear and adhesive colloidal solution. As a binder solution, HPMC can effectively reduce the contact angle of the drug, facilitate the wetting of the drug, and its swelling coefficient can reach hundreds of times after absorbing water, significantly improving the disintegration and release rate of the drug. For example, there is a literature study that replaces the original binder starch paste in the ibuprofen formulation with HPMC, which can effectively improve the dissolution of poorly soluble drugs and improve the quality of the tablet. 1) As a binder and disintegrant in tablets
Another advantage of using HPMC as a binder is as follows: Firstly: We all know that the hygroscopicity and moisture content of the binder can affect the stability of the tablets during storage. Hygroscopicity may cause the formulation to agglomerate, deliquesce, undergo crystal transformation, etc., which may further affect the content and dissolution of the formulation, and the tablets after hygroscopicity will be more prone to mold, oxidation, hydrolysis, etc. Therefore, it is advisable to select some types of excipients with lower hygroscopicity. Studies have shown that in a production environment with a relative humidity of 50% or below, the balanced moisture content of PVP and CMC-Na is approximately 18% and 15% by weight ratio, while the cellulose series such as HPMC, HPC, EC, etc. are generally 5% or less. Therefore, it can be regarded as an advantage; Secondly, the commonly used other binder PVP contains a relatively high content of peroxides. Peroxides will directly react with easily oxidizable drugs to generate free radicals, thereby affecting the stability of the drug. Therefore, for this type of drug, it is recommended to use cellulose-based HPMC with lower peroxide content.
2) HPMC can be used as a film coating material
HPMC is favored due to its excellent film-forming properties, resulting in a film with appropriate strength, permeable coating layer, and low brittleness. The film coating is stable under light, heat, and certain humidity conditions, and it can be dissolved in organic solvents and water. It has a relatively small adverse effect on the disintegration and dissolution of tablets. Therefore, it is a widely used and highly effective film coating material for gastric solubility. Among coating materials, HPMC is often combined with pigments, light blockers, and plasticizers in a certain proportion to form a complex. Before use, it is dissolved in a solvent or uniformly suspended and then applied for coating. For example, there have been studies on the application of HPMC in gentamicin film-coated tablets. Since gentamicin has strong hygroscopicity, the quality of the tablets is unstable, prone to cracking and discoloration, and the storage period of the tablets is relatively short, only about one year. However, when HPMC is used for gentamicin film coating, it can to some extent overcome the discoloration and cracking behavior inside the tablet core, and the accelerated experiment results for six months prove that the various performance of the HPMC film coating is superior to that of the sugar-coated tablets.
3) The application of HPMC as a material for capsule shells
Currently, HPMC is also commonly used in the production of capsule shells. Compared with gelatin capsule shells, it has significant advantages. Firstly, it can overcome the cross-linking effect of gelatin. Secondly, because the water content of HPMC is much lower than that of gelatin material (the water content of gelatin material is generally 12.5-17.5%), the water content of HPMC is only 4% to 5%. Unlike the gelatin shell material, which has a water content of 12.5-17.5%, if the content is highly hygroscopic, the gelatin shell will lose water and lose its original toughness. Therefore, using HPMC capsule shells is more suitable for contents with strong hygroscopicity or those more sensitive to moisture. It can effectively extend the shelf life of such products.
4) HPMC can be used as a suspending agent and stabilizer
HPMC can increase the viscosity of the liquid dispersion medium, reduce the interfacial tension between the solid and liquid phases, thereby enabling the suspension to remain in a stable state. Moreover, it can form a protective film on the surface of insoluble particles, effectively preventing the aggregation of particles and delaying the sedimentation rate of particles. Therefore, it is often used as a stabilizer in ophthalmic preparations. Some literature studies have screened the types of stabilizers for acyclovir eye suspension, and various types of stabilizers were selected. The results showed that the sedimentation volume ratio of Prescription 6 (HA/HPMC combination used as a stabilizer) was the largest, and the particle size range was smaller, with more uniform and fine particles. Therefore, in this prescription, 0.05% HA and 0.05% HPMC 4000 were preferred as stabilizers for use.
5) The application of HPMC as a hydrophilic matrix material in sustained-release tablets
In recent years, with the continuous in-depth exploration of drug delivery systems, people have gradually discovered that high-viscosity HPMC is often used as a hydrophilic gel matrix material in sustained-release formulations. The most commonly used one is the HPMC K series. Generally speaking, the higher the viscosity of HPMC, the greater the viscosity of the gel layer formed after encountering water. Then, the speed at which water-soluble drugs are released from the matrix is slower. Usually, the ratio of HPMC to the drug is controlled to control the release rate of the drug. Generally speaking, the release rate of the drug will decrease as the proportion of HPMC increases. Because as the amount of HPMC increases, the thickness of the gel layer also increases, which leads to a slower drug release rate. Of course, one cannot simply increase the amount of HPMC to control the drug release rate while ignoring the issue of tablet weight. If the tablet weight is too large, the patient's medication compliance and acceptability will be poor. For example, for water-soluble drugs, merely adjusting the ratio of the drug to HPMC is difficult to achieve satisfactory release effects. In such cases, it may be necessary to add some other excipients to delay the drug release rate. For instance, there is a literature study that investigated the effects of different viscosities and dosages of HPMC on the drug release rate in hydrophilic gel matrix sustained-release tablets of diclofenac potassium. The results showed that the release rate of the drug slowed down as the viscosity and dosage of HPMC increased. Finally, based on the prescription requirements, the dosage of the matrix material HPMC-K4M was selected as 40%.
Of course, there are studies that show in sustained-release preparations, HPMC is not the case where the higher the viscosity, the better. Because the higher the viscosity of HPMC, the slower its hydration rate, which can easily lead to sudden release at the early time points, while the amount of drug release in the later stage is insufficient. (Generally speaking, the hydration rate of HPMC decreases as the viscosity increases. The one with a faster hydration rate has a faster local expansion after water infiltration, thereby quickly exerting the controlled-release effect). Therefore, it is possible to consider using different viscosities of HPMC in combination, that is, the low-viscosity HPMC has a faster hydration rate, which is conducive to controlling the release rate at the early time points, while the high-viscosity HPMC has a slower hydration effect, based on controlling the release rate at the later time points.
In conclusion, due to its excellent physical and chemical properties, HPMC has been widely applied in the pharmaceutical industry. The above only lists a few of its applications. It can also be used as a carrier for solid dispersions or a thickening agent for gel preparations, etc. This article does not provide a detailed list. We believe that with further in-depth research on HPMC, its application fields will gradually expand, promoting its multi-field and multi-directional development.
