Study on the performance of compound system of hydroxypropyl methylcellulose and starch ether

Abstract: High-viscosity hydroxypropyl methylcellulose (HPMC) and hydroxypropyl starch ether (HPS) were compounded according to different mass fractions, and NDJ. Type 1 rotational viscometer and Anton Paar Physica MCR 301 rheometer to study its viscosity and rheological properties, as well as the change law of light transmittance and water retention. The results show that with the increase of the HPS compound content, the viscosity and light transmittance of the compound sample tend to decrease gradually, but the viscosity is relatively stable in a large shear rate range, showing good shear resistance. Cutting property; after adding HPS, the water retention rate of the composite sample was significantly higher than that of the single HPMC product, and with the increase of HPS content, the water retention rate went through a process that first increased significantly, then decreased slowly, and then increased slowly. Reasonable selection of the viscosity and compound of HPMC, and a certain proportion of compounding according to the viscosity of HPMC can meet the needs of pharmaceutical capsule applications at a lower cost.

Key words: hydroxypropyl methylcellulose; hydroxypropyl starch ether; viscosity; rheology; water retention; light transmittance

Hydroxypropyl methylcellulose (HPMC) is a cellulose variety whose output and consumption have been increasing rapidly in recent years. HPMC is made of refined cotton after alkalization treatment, using propylene oxide and methyl chloride as etherification agents, through a A non-ionic cellulose mixed ether produced by a series of reactions. The degree of substitution is generally 1.2 to 2.0. Due to the different ratios of methoxyl and hydroxypropyl content and different viscosities in HPMC, it becomes various varieties with different performances. In medicine, HPMC can be widely used as film coating, slow-release agent and binder of pharmaceutical preparations, and another important use is the base material of pharmaceutical capsules. Experiments have proved that HPMC vegetable capsules have the following advantages compared with gelatin capsules:

1) Low water content. Since vegetable capsules use HPMC as the capsule material, the water content in the shell is lower than that of gelatin, and the appearance and dissolution rate are not sensitive to changes in the water in the shell and the ambient humidity, and the product quality is easier to control.

2) Low water vapor transmission rate, low static electricity, high temperature resistance and chemical inactivity, compatible with many products.

3) Wide applicability. HPMC cellulose belongs to cellulose derivatives, there is no risk of cross-linking reaction of amino acids in gelatin, the drug release rate is relatively stable, individual differences are small, and the stability is high.

4) Low requirements for storage conditions. It is almost not brittle in a low humidity environment, and has good stability at high temperatures. It does not have high requirements on the temperature, humidity and packaging materials of the storage environment.

5) It has good coating properties, and is especially suitable for the preparation of sustained and controlled release coated capsules. Due to the good affinity between HPMC and most polymer materials, the coating material is easy to adhere to the vegetable capsule with good uniformity.

6) Complete varieties and specifications, standard size, suitable for mechanical processing, in line with existing models of capsule filling machines, and no need to replace new machine parts.

7) It is very attractive to vegetarian products and meets the needs of special cultures.

However, physical compounding technology and chemical modification technology are the main ways to reduce its cost and improve its overall performance.

Etherified starch refers to the starch-based ether formed by the etherification reaction between the hydroxyl group in the starch molecule and the reactive substance under alkaline conditions, mainly including non-ionic starch and ionic starch. Etherified starch includes various types of products, such as carboxymethyl starch ether (CMS), hydroxypropyl starch ether (HPS), hydroxyethyl starch ether (HES), cationic starch ether, etc. Industrially produced non-ionic starches are mainly hydroxyethyl starch and hydroxypropyl starch. Hydroxypropyl starch ether can be obtained by reacting starch with propylene oxide or epichlorohydrin under alkaline conditions. Hydroxypropyl has good hydrophilicity and can provide excellent water retention performance of starch paste. Hydroxypropyl is non-ionic and is less affected by electrolytes. It can be used in a wide range of acid-base pH conditions, and has high stability in replacing ether bonds. Substituents are safe during chemical reactions such as hydrolysis, oxidation, and cross-linking. Won't fall off. Taking advantage of this property, it can be subjected to compound denaturation processing and controlling the degree of substitution to obtain products with different characteristics.

In the 1980s, the variety of modified starch was relatively single, mainly oxidized starch and pregelatinized starch. Up to now, domestic modified starch manufacturers have been able to produce almost all kinds of modified starches, which are widely used in medicine, papermaking, feed, food, adhesives and other industries.

In this paper, high-viscosity HPMC and HPS are compounded in different proportions, and the viscosity, light transmittance, water retention and rheological properties of the compound are tested to find out their regularity and trend, in order to Better guide production and application to the market.

1. Experiment

1.1 Instruments and equipment

NDJ． Type 1 rotational viscometer (Shanghai Precision Scientific Instrument Co., Ltd.); UV-757CRT ultraviolet-visible spectrophotometer (Shanghai Precision Scientific Instrument Co., Ltd.); AntonPaarPhysicaMCR 301 rheometer (Anton Paar, Austria)

Ltd.).

Ring mold; constant temperature water bath, temperature 20+0.2°C; thermometer, temperature range 0-50"C, accuracy 0.1°C.

1.2 Materials and reagents

150,000 hydroxypropyl methylcellulose, hydroxypropyl starch ether, all made by KIMA CHEMICAL CO., LTD; citric acid, gypsum powder, provided by Beijing Longshun Chemical Technology Co., Ltd.

1.3 Experimental method

1.3.1 Compounding

Compound hydroxypropyl methylcellulose and hydroxypropyl starch ether according to the mass ratio of 95:5, 90:10, 85:15, 80:20, 75:25, and mix well.

1.3.2 Viscosity test

Weigh 2.4 g of HPMC, HPS and each compound sample dried at 105±2°C for 2 h, accurate to 1 mg, and put the samples into seven 250 mL beakers respectively. Add a certain amount of hot water at 80-90°C to 7 beakers, swell for 5-10 minutes, then put them into cold water (or ice water) at 0-5°C, stir well to make it dissolve, add water to dilute to the mass fraction as a 1% solution. Put 7 beakers in a constant temperature water bath at 20±0.2°C for 1 h, take them out, stir them by hand for 10 s, and use NDJ. The viscosity was measured with a type 1 rotational viscometer.

1.3.3 Light transmittance test

The 1% aqueous solutions of the above samples were poured into 1 cm cuvettes, and the light transmittance was measured at 580 am with a UV-757CRT ultraviolet-visible spectrophotometer.

1.3.4 Rheology test

Using AntonPaarPhysicaMCR 301 rheometer, at 20±0.2°C, the 1% aqueous solution of the above samples was subjected to a variable shear test of 0.1-100 s-1 with a cone and plate, and the viscosity and shear stress were recorded as The curve of shear rate change.

1.3.5 Water retention test

Refer to the test method of water retention rate in the national standard GB/T3183-2003: Weigh 0.15 g of HPMC, HPS and each compound sample, 0.15 g of citric acid and 100 g of gypsum powder, and then dry mix them evenly, a total of 7 mixed samples. Mixed samples

All carried out according to the following procedure: take a certain quality of absorbent paper, place it on a glass plate, and buckle the ring die on the absorbent paper (with the mouth facing down). Put the dry-mixed sample into a beaker, add 80 mL of water, let it stand still for 1.5 min, stir rapidly in the beaker for 1 min, pour it into a ring mold and let it stand still for 3.5 min. Hold the mouth of the ring die with a glass plate, turn it upside down slowly, take out the absorbent paper to weigh its mass, and do a blank experiment without cellulose at the same time.

2. Results and Analysis

2.1 Changes in viscosity after compounding

Under the condition of 20 ± 0.2 °C, the viscosity of 1% aqueous solution of HPMC, HPS and each compound sample was measured with NDJ-1 viscometer, and the viscosity change curve was drawn. The viscosity of 1% aqueous solution of HPS measured by NDJ-1 viscometer is 16mPa·S. Due to the relatively low initial viscosity of HPS, the viscosity of the 1% aqueous solution of HPMC and HPS compound mixed samples gradually decreased with the increase of HPS compound content.

2.2 Changes in light transmittance after compounding

At a wavelength of 580 nm, the 1 cm light transmittance of HPMC, HPS and the 1% aqueous solution of each compound sample were tested with a UV-757CRT ultraviolet-visible spectrophotometer, and the light transmittance change curve was drawn. The light transmittance of 1% aqueous solution of HPS in 1 cm is 64.6%. Since the initial light transmittance of HPS is relatively low, the light transmittance of the 1% aqueous solution of the HPMC and HPS compound mixed samples gradually decreases with the increase of the compound content of HPS.

2.3 Changes in rheology after compounding

Under the condition of 20±0.2℃, use the cone-plate system of Anton Paar Physica MCR 301 rheometer to conduct the variable shear test of 0.1-100 S-1 on HPMC and the 1% aqueous solution of each compound sample respectively. , respectively recorded the viscosity and shear stress as a function of shear rate.

It can be seen from the above that with the increase of HPS content, although the viscosity of the 1% aqueous solution of the compound sample showed a decreasing trend, its viscosity was relatively stable within a large range of shear rate changes; The change of the shear stress under the condition is small, showing better shear resistance performance.

2.4 Changes in water retention after compounding

Using gypsum powder, HPMC, HPS and various composite samples were tested for water retention rate, and the water retention rate change curve was drawn. The water retention rate of HPS is 23.71%. After HPMC and HPS are compounded in different proportions, the water retention rate is significantly improved compared with the single HPMC sample, which shows that after adding hydroxypropyl starch to HPMC, there is a certain synergistic effect, which makes the water retention rate have an overall improvement. In addition, with the increase of HPS content, the water retention of the compound sample increased significantly first, then decreased slowly, and then increased slowly, indicating that adding a small amount of hydroxypropyl starch can make the compound sample achieve a higher water retention rate. Then, with the increase of HPS content, there is a mutual coordination process between HPMC and HPS, that is, the water retention first decreases and then increases. From the above results, it can be seen that adding hydroxypropyl starch can effectively improve the water retention rate of the compound sample.

3. Conclusion

1) Due to the low initial viscosity and light transmittance of hydroxypropyl starch, with the increase of HPS compound content, the viscosity and light transmittance of the compound sample showed a trend of decreasing gradually, but the solution viscosity of the compound sample It is stable in a large shear rate range and exhibits good shear resistance.

2) After adding hydroxypropyl starch, the water retention rate of the compound sample is significantly higher than that of the single HPMC product, and with the increase of the HPS compound content, the water retention rate increases significantly first, then decreases slowly, and then increases slowly big process. It shows that there is a certain synergistic effect after adding HPS, so that the water retention rate has an overall improvement.

3) After adding hydroxypropyl starch, although the viscosity and light transmittance of the compound sample decreased to a certain extent, the solution viscosity of the compound sample was stable in a large shear rate range, and had good shear resistance. performance, and the water retention rate of the compound sample has an overall improvement compared with a single HPMC, and the market price of hydroxypropyl starch is lower, so the initial viscosity of hydroxypropyl methylcellulose and the type of compound are reasonably selected, and according to The initial viscosity of hydroxypropyl methylcellulose can be compounded in a certain proportion, which can meet the requirements of capsule liquid preparation at a lower cost.