Comparison of Domestic and Imported Hydroxypropyl Methyl Cellulose Used in Nifedipine Sustained Release Tablets

Abstract: Objective To compare the effect of domestic and imported hydroxypropyl methylcellulose (HPMC) in the preparation of sustained-release tablets. Methods Taking Nifedipine Sustained Release Tablets as a model drug, the physical and chemical properties, tablet preparation process and sustained release effect of domestic and imported HPMC were compared. Results It is not feasible to prepare sustained-release preparations with domestic high-viscosity HPMC, and cannot form stable sustained-release preparations like imported HPMC. Conclusion To use domestic high-viscosity HPMC in sustained-release preparations, further breakthroughs in technology are required; to improve the level of domestic preparations, the quality of domestic excipients must also be improved.

Key words: hydroxypropyl methylcellulose; domestic; imported; nifedipine sustained-release tablets; excipients

In recent years, hydroxypropyl methylcellulose (HPMC) has been widely used, and the price of imported products is about three times that of domestic products, which is related to the difference in performance between the two. The author has studied the different effects of domestic HPMC and imported HPMC when used in nifedipine sustained-release tablets, and the report is as follows.

1. Instruments and reagents

TDP single-punch tablet press (Beijing Sinopharm Longli Technology Co., Ltd.); UV-2501PC ultraviolet-visible spectrophotometer (Shimadzu, Japan); RCZ-6B intelligent dissolution tester (Shanghai Huanghai Drug Inspection Instrument Factory). Domestic HPMC (KIMA CHEMICAL CO.,LTD); Imported HPMC (U.S. Dow Company); Nifedipine (Tianjin Tianan Pharmaceutical Co., Ltd.).

2. Methods and Results

2.1 Model, appearance and physical and chemical properties

The domestic HPMC models are high-viscosity HPMC 75 RT4000 and HPMC 75 RT50, and the imported HPMC models are HPMC Methocel K4M. The appearance of the two is different, and the domestic HPMC 75 RT 4000 cannot completely pass through the 60-mesh sieve, and there are flocs, while the imported HPMC can completely pass through the 60-mesh sieve. The reason may be that there are differences in the production process between the two.

2.2 The influence of moisture

When the hydrophilic gel matrix tablet meets water, the surface hydration forms a gel layer, which is the primary condition for controlling drug release. When domestic high-viscosity HPMC and imported HPMC are used in sustained-release preparations, gels will be formed after absorbing water, which can reduce the drug release rate, but the sustained-release properties are different. After domestic HPMC is formed into a preparation, there is a big difference between when it is dried as much as possible and when it contains a certain amount of water, and the drug release becomes much faster; imported HPMC also becomes faster, but not so much. From the appearance, this is caused by flocs, which are difficult to mix in the material, so to obtain a stable release curve, the problem of flocs must be solved first. From the point of view of the drug nifedipine sustained-release tablets, using domestic high-viscosity HPMC as the sustained-release material, the initial release rate is slow, but after half a year at room temperature, the release rate becomes faster. The author has tried to obtain a stable release profile by controlling the water content and HPMC ratio, but found it difficult to maintain moisture.

2.3 Sustained release effect

Prepared with a certain amount of imported HPMC Methocel K4M, when the water content of the granules is 3.9%, the slow-release effect is obvious; when the same amount of domestic HPMC 75 RT4000 is used, the slow-release effect is acceptable when the water content of the granules is 4.9%. The two granules were baked at 60-65°C for 3-4 hours and then pressed into tablets to test the release rate. The imported HPMC 4000 still had a slow-release effect, although the release became faster, but the range was not large; the domestic HPMC 75 RT4000 had a poor slow-release effect The amount of HPMC 75 RT4000 can not be released according to the national standard of nifedipine sustained-release tablets, and the sustained-release effect is still not as good as imported ones. Therefore, from the perspective of cost performance, domestic HPMC 75 RT 4000 has no advantages, and there is a risk of unstable formulations.

Changing the use ratio of domestic HPMC 4000 and repeating the test, it is found that the law is not easy to grasp, and the release curve of nifedipine sustained-release tablets is always unstable.

3.Discussion

Using domestic high-viscosity HPMC 75 RT4000, although the preparation can retain a certain amount of water and have a slow-release effect, this effect is very unstable because the moisture will change with the change of the environment. When the preparation is baked to the lowest possible moisture, the domestic high-viscosity The sustained-release effect of HPMC is greatly weakened, which is related to the production process and quality control. The content of the hydrophilic group hydroxypropoxy is the main factor determining the hydration rate of HPMC, so different types of imported HPMC have different hydration rates, such as Methocel K>Methocel E>Methocel F. This is also the reason why Methocel K and Methocel E are widely used in matrix preparations. Sun Guoqing and others used domestic RT series HPMC (produced by KIMA CHEMICAL CO., LTD, equivalent to Methocel E) to make glipizide sustained-release tablets. They believed that the surface hydration rate was not fast enough to provide effective protection for the tablet core. Glipizide is released very quickly. This is consistent with the results of this experiment. It is also believed that the sustained-release effect of the matrix tablet made of HPMC RT4000 on water-soluble propranolol hydrochloride is similar to that of Methocel K4M. Although the combination of domestic HPMC 75 RT4000 and HPMC 75 RT 50 in a certain proportion may also have a sustained release effect. However, according to the sustained-release test of domestic high-viscosity HPMC 75 RT 4000, the release uniformity and stability of the sustained-release preparations made with it are not as good as the imported ones, and the technical risk is high. The price/performance ratio is not high.

At present, the application of domestic high-viscosity HPMC as a film-coating material in gastric-soluble coating is very successful, but it is not feasible to prepare sustained-release preparations. A stable sustained-release formulation could not be obtained. In order to use domestically produced high-viscosity HPMC 4000 in sustained-release preparations, further research on its synthesis process is required to break through the shortcomings of the existing technology.