The major ingredient of hard gelatin (what is hard gelatin) is the hydrolyzed form of animal collagen, usually obtained from cow bone (65% raw material origin) or pig skin (30%), hydrolyzed after acid (pH 1.5-3.0) or alkali (pH 8-12) treatment. The content of residual collagen is 85-92% (European Pharmacopoeia standard). Its chemical composition consists of 18 amino acids, glycine (33%), proline (12%) and hydroxyproline (10%) were most abundant, and its molecular weight range is 15,000-250,000 Da (results of gel permeation chromatography). ISO 9665 states that hard gelatin must contain ash content ≤2%, moisture ≤15%, and sulfur dioxide residue ≤50ppm (food grade quality standards).
Of physical properties, the strength of gel (Bloom value) of hard gelatin is most crucial, usually 150-300 Bloom (test condition: 6.67% concentration, cooling at 10 ° C for 17 hours). For example, pharmaceutical grade gelatin, such as Rousselot GP-1, has a Bloom value of 250±10 and viscosity of 3.5-4.5 mPa·s (at 20 ° C), suitable for the production of capsule shells (pass rate ≥99.5%). In 2023, the global hard gelatin market will be 3.2 billion US dollars, 60% of which will be allocated to capsule manufacturing (Grand View Research data), with a single capsule shell being 20-150mg (equivalent to capsules 00 to 5) and costing around 0.002-0.005 US dollars/capsule (Capsugel production report).
The chemical stability of hard gelatin was mostly dependent on environmental conditions. At a humidity of > 60% RH, the water content in the capsule increases from 10% to 18%, causing softening and adhesion of the capsule shell (adhesion rate > 5%). At temperatures > 40℃, the crosslinking reaction of the gelatin is accelerated and the disintegration time is extended from 15 minutes to 40 minutes (USP<701> dissolution test). In 2021, Pfizer initiated a voluntary recall of a batch of amoxicillin capsules as they were inadequately stored in the tropics (temperature 30 ° C/humidity 75% RH) and incurred a loss of $2.7 million (FDA warning letter case).
what is hard gelatin? Regulatory requirements are stringent. The European Union requires the rest of the limit of heavy metals to be lead ≤5ppm and arsenic ≤1ppm (EDQM standard), while in the US FDA, the microbial index should meet the total number of colonies ≤1000 CFU/g, and no detection of salmonella (21 CFR 184.1975). In 2022, an Indian producer stopped production of the capsule-making line due to high chromium of raw material gelatin (test value 6.8ppm, standard ≤2ppm), incurring a direct loss of $480,000 (WHO supply chain audit). Under environmental pressure, Rousselot launched carbon-neutral gelatin (35% lower carbon footprint) at a 12% increased cost in comparison with traditional products (Sustainable Materials Summit 2023 data).
Competing materials’ competition is revolutionizing the industry. Vegetarian demand will increase plant-based hard capsules (e.g., hydroxypropyl methylcellulose, HPMC) market share to 22% in 2023 with a 14% annual growth rate, but their tensile strength is still less than that of gelatin capsules (25-30 MPa) at 15-20 MPa. what hard gelatin is supplemented by modification steps such as crosslinking degree control, such as Capsugel’s DRcaps™ enteric gelatin capsule disintegrating ≤30 minutes at pH≥6.8, 40% faster than HPMC enteric gelatin capsules (Journal of Drug Controlled Release research).
In the future perspective, what is challenging in gelatin nano technology (particle size ≤100nm) can improve the bioavailability by 20%-50%, but the production cost increases by 25% (International Pharmacy paper). Lonza is investing $120 million in 2023 to make genetically modified collagen with the target of reducing the gelatin manufacturing cycle from 30 days to 7 days and reducing carbon emissions by 60 percent (Reuters Business News). Yet hard gelatin will still maintain a dominant position in pharmaceutical production and food processing with the global demand estimated to hit 680,000 tonnes (4.3% CAGR) by 2030, led by vaccine capsules such as COVID-19 mRNA vaccines with penetration of more than 75% (Frost & Sullivan estimate).