hard gelatin capsules mainly contain animal gelatin, plasticizer and water, wherein gelatin is about 80-90% (cow bone or pig skin derived, freezing power value 150-280 Bloom), glycerin or sorbitol as plasticizer is 8-12%. Moisture control of 13-16% for the sake of capsule shell flexibility (breaking strength ≥8 N). According to USP requirements, gelatin must meet microbial limits (aerobic bacteria ≤1000 CFU/g, mold ≤100 CFU/g), heavy metal residues (lead ≤0.5 ppm, arsenic ≤0.1 ppm). In 2023, Capsugel’s Vcaps® series capsules, which are manufactured from bovine bone gelatin (hydroxyproline content ≥12%), have a stable disintegration time of 10±2 minutes at elevated temperatures (40°C), 60% more stable than pig skin gelatin (disintegration variation ±5 minutes).
Production process parameters have direct effects on capsule properties. Gelatin solution concentration normally 28-32%, viscosity 3.5-4.5 Pa·s (measured at 40°C), impregnated using stainless steel mold (capsule size 5, which corresponds to 4.91 mm), drying temperature gradient 25-35°C, humidity gradient 20-40%RH, molding cycle about 45 minutes. Lonza, Switzerland Quali-V® production line narrows the capsule shell thickness deviation to ± 0.02mm through closed-loop temperature control (±0.5°C), and the locking force is increased to 15 N (industry average 10 N), with a yield of 99.5%. Pfizer polished the mold (Ra≤ 0.4μm) in 2021, reducing the capsule closure failure rate from 0.3% to 0.05%, with $1.8 million in annual cost savings.
Additives impart functionality and compliance. Titanium dioxide (0.5-2%) shading agent can make the shading rate of the capsule ≥90%, suitable for use in photosensitive drugs (e.g., nifedipine); Colorant (e.g., iron oxide red) must comply with FDA 21 CFR 73.1200 standard, migration ≤1.0 μg/cm². In 2022, Catalent’s DRcaps™ enteric capsule, based on the combination of hydroxypromethcellulose (HPMC, 15%) with gelatin, resists gastric acid (pH 1.2) for ≥2 hours, intestinal release time deviation ≤±5%, and bioavailability is enhanced by 25%. Vegetarian capsules (e.g., Lonza VCaps® Plus) replace gelatin by hydroxypropyl starch, but tensile strength is only 6 N (gelatin capsules ≥10 N), and the cost increases by 30%.
Regulation and environment drive material innovation. EU REACH regulation requires the residual amount of polycyclic aromatic hydrocarbons (PAHs) in gelatin to be less than 50 ppb and promotes the upgrading of the purification process (activated carbon adsorption rate ≥99%). In 2020, Japanese chemical manufacturer Nitta Gelatin will occupy 35% of the global high-end injection-grade capsule market by developing low endotoxin gelatin (≤ 0.25EU /mg). During COVID-19, the market demand for hard gelatin capsules was boosted (1.8 trillion capsules were manufactured worldwide in 2021, and the growth rate was 12%), and the price of raw gelatin rose from $8 /kg to $14 /kg, so companies had to use recycled gelatin (less than 10%) to reduce expenses. However, ensure the gel strength ≥200 Bloom.
Sustainable development challenges and solutions. The production of 1 ton of gelatin capsules requires 6 tons of fresh aggregate, and COD emission of wastewater is less than 500 mg/L. In 2023, CapsCanada in France launched the EcoCaps® series, which reduces the energy consumption of gelatin extraction by 40% and carbon by 25% through enzymatic hydrolysis process (compared to traditional acid method). China Erkang Pharmaceutical developed starching-gelatin composite capsules (30% starch content), with improved delixing resistance (deformation rate ≤0.3% under the condition of humidity ≥ 70%RH), but the market penetration rate was only 2%, due to the fact that the disintegration time was extended to 15 minutes (normal capsules 10 minutes). According to Grand View Research, in 2030 the global hard gelatin capsules market will be valued at $4.9 billion and the market share of eco-friendly materials will increase to 18%.