Dissolving Technology of Hydroxypropyl Methyl Cellulose and Its Application in Eye Drops

Abstract: Purpose: To obtain the maximum viscosity and clarity of hydroxypropyl methylcellulose solution, which is used as a thickener for eye drops. Method: Fully disperse in hot water, flush with water at room temperature, and place in a cold place for 48 hours. Results: Using the above process to dissolve propylmethylcellulose, the solution with maximum viscosity and clarity was obtained. Conclusion: The dissolution process is worth popularizing.

Key words:hydroxypropyl methylcellulose; dissolution; process; eye drops

Hydroxypropyl methylcellulose is a non-toxic and safe pharmaceutical excipient widely used. It has the characteristics of emulsifying, thickening, suspending, viscosifying, gelling, film-forming and compatible with other substances. The application form of hydroxypropyl methylcellulose in the pharmaceutical industry is mainly its aqueous solution. Like the dissolution process of all polymers, water molecules must fully contact hydroxypropyl methylcellulose and diffuse into hydroxypropyl methylcellulose. In the solid particles of cellulose-based cellulose, a uniform solution can only be obtained after the entanglement between the hydroxypropyl methylcellulose molecules is released. The preparation of hydroxypropyl methylcellulose aqueous solution adopts different processes to obtain solutions with different viscosities and clarity. The author has conducted research on its dissolution process, which is reported as follows.

1. Instruments and samples

UV-1221 ultraviolet spectrophotometer (Beijing General Equipment and Instrument Factory); viscometer: American Bolifei DVⅡ+ programmable viscometer; 65RT50 hydroxypropyl methylcellulose (KIMA CHEMICAL CO., LTD).

2. Prescription and preparation

2.1 Prescription

Hydroxypropyl methylcellulose: 20 g; water for injection: add to 1000 ml.

2.2 Preparation

2.2.1 Flushing method

Take 1/3 of the prescribed amount of water for injection at 80-90°C, add the prescribed amount of hydroxypropyl methylcellulose into the water, and stir for 15 minutes as it is added to form a uniform insoluble paste, then add the remaining amount of room temperature injection Make up to the full amount with water, stir for 15 rain, place in a refrigerator at 2-10°C for 48 h, take out the solution and bring it to room temperature, measure the dynamic viscosity (No. 18 rotor, 35 rpm) and light transmittance (400 am, 310 nm) as sample 1.

2.2.2 Direct dissolution method

Take the prescribed amount of water for injection at room temperature, weigh the prescribed amount of hydroxypropyl methylcellulose, add the hydroxypropyl methylcellulose to the water, and stir for 30 min as it is added. Place it in a refrigerator at 2-10°C for 48 hours, take the solution out to room temperature, measure the dynamic viscosity (No. 18 rotor, 35 rpm) and light transmittance (400 Flm, 310 nm) as sample 2.

2.3 Test results

3.Discussion

The dissolution method of hydroxypropyl methylcellulose, hydroxypropyl methylcellulose is soluble in cold water but not in hot water. However, it is difficult to disperse and dissolve it directly in cold water. Even if it is stirred for a long time, a uniformly dispersed and transparent solution cannot be obtained. Water molecules continue to infiltrate. When the author adopts the direct dissolution method, after stirring for 30 minutes, there are still some large sticky pieces of hydroxypropyl methylcellulose wrapped in water on the surface and dry powder inside. The use of the pulping method is conducive to the uniform dispersion of water molecules among the hydroxypropyl methylcellulose molecules and dissolution. After the hot water forms a uniform paste, when adding room temperature water, it becomes a uniform, slightly tiny transparent hydroxypropyl methylcellulose solution.

Some water soluble polymers. It is often placed at room temperature for 48 h after dissolving to fully hydrate, and a solution with maximum viscosity and clarity can be obtained. The author adopts the condition of 2 ~ 10 ℃ to place it, which can avoid the operation process of cooling the room temperature water first, which is especially suitable in large-scale production. Hydroxypropyl methylcellulose is stable in a dry environment, but its aqueous solution is easily contaminated by microorganisms, so it is fully dissolved at low temperature.

4. Application of hydroxypropyl methylcellulose in eye drops

Obtaining maximum viscosity and clarity of hydroxypropyl methylcellulose solution is important for its application in ophthalmic medicine.

Eye drop preparations generally use many excipients, such as adjusting the pH value at 5.0-9.0, adjusting the osmotic pressure in the isotonic range, adding bacteriostats to prevent microbial contamination, and some drugs need to add solubilizers, stabilizers, etc. The pH of the 1% solution of hydroxypropyl methylcellulose is 4-8, the viscosity is stable in the range of pH 3.0-11.0, and it has good compatibility with electrolytes. It is suitable for use as a thickener in eye drops . The use concentration is 0.45% to 1.0%. It can prolong the contact time with the eyeball, increase the absorption of the drug, and improve the bioavailability.

Hydroxypropyl methylcellulose is often used as a suspending agent in suspension eye drops, which can increase the viscosity of the solvent, reduce the density difference between the particles and the dispersion medium, and increase the hydrophilicity of the particles. Suspended particles are affected by gravity and will naturally settle when left standing. The settling velocity conforms to Stokes' law. The settling velocity is inversely proportional to the viscosity of the dispersion medium and proportional to reducing the density difference between the particles and the dispersion medium. In addition, this product is used as a gel base in gel eye ointment.

Hydroxypropyl methylcellulose can reduce the surface tension and interfacial tension of the water dispersion system by 18-30 raN/‰. It has a moderate emulsifier effect on the dispersion system, and the dosage is as low as 0.001%-1.0%. Next, it is an effective surfactant. The use of hydroxypropyl methylcellulose in eye drops can reduce the surface tension of eye drops, increase the permeability to the cornea, increase the absorption of drugs, improve bioavailability, and make the liquid reach the nasal mucosa. The speed is slowed down to reduce the side effects caused by the systemic absorption of the drug.