The Production Process Of HPMC Hollow Capsules

Hydroxypropyl methylcellulose hollow capsules are plant capsules made mainly from hydroxypropyl methylcellulose, which have the advantages of no animal origin, good low humidity stability, and suitability for sensitive drugs. They are widely used in the fields of medicine, health products, and food. The production process mainly includes key steps such as raw material preparation, sol, billet making, drying, cutting, and nesting. The following is a detailed process flow and technical points:

1, Raw material preparation

Main raw material hydroxypropyl methylcellulose (HPMC): Pharmaceutical grade HPMC is selected, with a viscosity range of usually 3-100mPa · s (2% aqueous solution, 20 ℃), and the viscosity is adjusted according to the capsule specifications.

Hydroxypropyl content (7.0% -12.0%) and methoxy content (28.0% -30.0%) must comply with pharmacopoeial standards (such as USP/NF, EP, or ChP).

Plasticizer: Glycerol or sorbitol is commonly used, with an addition amount of 10% -30% of the dry weight of HPMC, to adjust the flexibility and anti brittleness of capsule films.

Water: Use deionized water or purified water with a conductivity of ≤ 1.3 μ S/cm to avoid impurities affecting the quality of the capsules.

Auxiliary raw materials (optional) coloring agents: such as titanium dioxide (white), iron oxide (red/yellow), or chlorophyll (green), must meet pharmaceutical standards.

Sunscreen: such as titanium dioxide (added at a dosage of 0.5% -2%), to prevent degradation of photosensitive drugs.

Preservatives: such as parabens (with an addition amount of ≤ 0.05%), extend the storage time of the sol.

2, Sol (preparation of gel solution)

Preparation steps: Dry mix HPMC with plasticizers, coloring agents, and other dry powders evenly (stirring speed 50-100rpm, time 10-15 minutes).

Swelling: Slowly add the dry mixture to water preheated to 60-70 ℃ (while stirring) to form a uniform suspension.

Dissolve: Continue stirring and heating to 80-90 ℃, keep warm for 30-60 minutes until HPMC is completely dissolved, forming a transparent or semi transparent adhesive solution.

Defoaming: Use a vacuum defoamer (vacuum degree ≥ -0.08MPa) to remove bubbles from the gel solution and avoid surface defects on the capsule.

Key control point temperature control: Excessive dissolution temperature may lead to HPMC degradation, while insufficient temperature may result in incomplete dissolution.

Viscosity adjustment: Adjust the viscosity of the adhesive solution by adding a small amount of water or HPMC (usually 2000-5000mPa · s, 25 ℃) to ensure subsequent molding stability.

PH value: The pH value of the gel solution should be controlled between 5.5-7.5 to avoid acidic or alkaline environments affecting drug stability.

3, Raw material (capsule film forming)

Preparation of immersion method (traditional process) mold: Capsule molds (needle molds) made of stainless steel or chrome plated steel are used, with a smooth and scratch free surface.

Immersion: Immerse the mold in the adhesive solution (depth of about 5-10mm, time 2-5 seconds), so that the adhesive solution evenly adheres to the surface of the mold.

Pulling: Pulling the mold at a constant speed (50-100mm/s) to form a uniform thin film of adhesive under the action of gravity.

Pre drying: Pre dry in a hot air circulating oven (temperature 40-50 ℃, humidity ≤ 30%) for 10-15 minutes to preliminarily shape the capsule film.

Rotating molding method (modern technology) glue spraying: The glue is evenly sprayed onto the surface of a rotating cooling drum (temperature 10-15 ℃) through a high-pressure nozzle to form a thin layer.

Stripping and molding: Use capsule molds to press the adhesive film, and after peeling, form a capsule body, which is 3-5 times more efficient than the immersion method.

Advantages: Better uniformity of film thickness (± 5 μ m), suitable for large-scale production.

4, Drying and solidification

Segmented drying initial drying stage: temperature 40-50 ℃, humidity ≤ 30%, time 2-3 hours, remove surface moisture, prevent capsule adhesion.

Main stage: Temperature 50-60 ℃, humidity ≤ 20%, time 4-6 hours, allowing the moisture inside the capsule to slowly evaporate to avoid stress cracking.

Final drying stage: temperature 60-70 ℃, humidity ≤ 10%, time 1-2 hours, ensure residual moisture ≤ 8% (in accordance with pharmacopoeia standards).

It is recommended to use tunnel drying oven or continuous mesh belt dryer for drying equipment to achieve precise control of temperature, humidity, and wind speed.

Avoid local overheating that may cause deformation or uneven color of the capsule.

5, Cutting and fitting

Cut the dried capsule film into capsule body and capsule cap according to the preset size using laser or mechanical cutting machine.

The cutting accuracy should be controlled within ± 0.1mm to ensure a tight fit.

The capsule body and cap are aligned and pressed together by an automatic laminating machine, and the laminating force must meet the standard (usually 10-30N).

The length deviation of the capsule after fitting should be ≤ 0.3mm, and the opening degree should meet the design requirements (such as the opening diameter of capsule 0 ≥ 5.5mm).

6, Quality Inspection and Packaging

Online appearance inspection: Remove capsules with bubbles, cracks, color spots, or deformations.

Weight detection: Use an automatic weighing instrument to screen capsules with a weight deviation exceeding ± 5%.

Wall thickness detection: Ensure wall thickness uniformity (± 10 μ m) through a laser thickness gauge.

Laboratory moisture testing: using Karl Fischer method or drying weight loss method, residual moisture should be ≤ 8%.

Dissolution test: Simulate the in vivo environment to detect the capsule dissolution time (usually 10-30 minutes).

Microbial limit: Complies with pharmacopoeia standards (such as total bacterial count ≤ 1000 CFU/g, mold and yeast count ≤ 100 CFU/g).

The packaging is sealed in aluminum foil bags or plastic bottles, with desiccant inside, and stored away from light.

Storage conditions: temperature 15-25 ℃, humidity ≤ 60%, and shelf life is usually 24-36 months.

7, Process optimization direction

Environmental improvement: Using water-based adhesive instead of organic solvents to reduce VOC emissions.

Intelligent upgrade: Introducing machine vision and AI algorithms to achieve real-time quality monitoring and reduce defect rates.

Functional expansion: Develop enteric coated or sustained-release HPMC capsules, achieve targeted release by adjusting HPMC viscosity or adding functional excipients.

8, Common Problems and Solutions

Reason for capsule brittleness: Insufficient plasticizer or too fast drying.

Solution: Increase the amount of glycerol or extend the drying time.

Reason for capsule adhesion: Insufficient drying or high environmental humidity.

Solution: Increase the final drying temperature or reduce the environmental humidity before packaging.

Reasons for uneven film thickness: unstable immersion speed or fluctuation of adhesive viscosity.

Solution: Optimize the lifting mechanism or install an online viscosity meter for real-time control.

Through strict temperature control, humidity control, and precise process parameter settings, hydroxypropyl methylcellulose hollow adhesive