Usual capsule sizes follow the international numbering system from 000 to 5, a total of 8 sizes whose length and diameter directly affect the drug loading capacity and processability. Taking gelatin capsules as an example, capsule No. 000 has the largest volume (1.37mL), being 23.3mm long and 9.91mm in diameter, suitable for filling light powder (for example, antibiotic apis) with a bulk density ≤0.4g/cm³, while capsule No. 5 is only 0.13mL in volume, 11.1mm long and 6.63mm in diameter. For application to high active content levels (e.g., endocrine products). The global market capsule 0 (0.68mL) is used at 42% because it’s well balanced with loading capability (0.3-0.6g) and swallowing comfort for the patient (89% adult rate), according to Pharmaceutical Technical Manual 2023. Pfizer specifications state that ibuprofen sustained release tablets use capsule 0 filling speed of 2,800 capsules/minute, pass rate of 99.1%, and shift to capsule 1 (0.50mL) when speed is increased to 3,200 capsules but have the additional need of incorporating 15%-20% of microcrystalline cellulose for achieving bulk density of ≥0.6g/cm³, thus 12% higher raw material cost.
Capsule sizes have strong associations with production parameters. The German Bosch GKF 2700 machine accommodates capsule production from 000 to 4, for which 5 calls require an investment of another $80,000 in upgrading the mold module, and a further tightening of the requirement of filling precision from ±5% to ±3% requires an additional increase in energy consumption from 2.8kW to 4.2kW. The cost difference is significant: the unit price for gelatin capsule 0 is $0.028 / capsule, whereas that of the gelatin capsule 5 is only $0.009, but to load the same titer of drug, the API level of the gelatin capsule 5 needs to be increased by 30%, and the process validation cycle is extended from 6 weeks to 12 weeks. The 2024 Novartis case proved that the change of the antihypertensive drug from 00 (0.95mL) to 2 (0.37mL) capsule saved the package cost by 18%, while the particle size decreased from 250μm to 80μm, the brittle failure rate increased from 0.7% to 2.3%, and the annual quality loss was $240,000.
Dimensional accuracy is driven by regulatory demands. USP<7> stipulates that the tolerance of the capsule length is ±0.25mm and the diameter error is ≤±0.1mm. For example, the nominal capsule No. 3 size is 15.9mm, and the tested fluctuation should be kept at 15.65-16.15mm. The new EU 2025 regulation requires the plant capsules’ moisture expansion coefficient (HPMC) to be less than 1.5% (3.2% for gelatin), which requires the wall thickness of capsule 2 to increase from 0.08mm to 0.12mm, which requires the filling equipment pressure to be adjusted from 0.5MPa to 0.8MPa. The Japan PMDA dissolution test showed that the disintegration time standard deviation in pH1.2 medium for capsule No. 4 was 2.1 min (capsule No. 0 was 3.8 min), which led to further designs of small size for the sustained-release products.
Subdivision size innovation has been driven by market demand. The pediatric formulation prefers to use capsule No. 4 (92% swallowing success), but the loading of API must be carried out to 80mg via the nanocrystalline process, and Q30 dissolution must be ≥85%. Capsule No. 1.5 (0.45mL) of 2023 produced by Johnson & Johnson is a segmental type that is capable of loading enteric-soluble and rapid-release particles with a difference of ±2.5% simultaneously, but the production rate is reduced to 2,100 capsules/min. Increased demand for 1,200μm capacity of drug particle-carrying veterinary Animal Medicine 000 capsule, but equipped with a 5.5kW vibratory packing mechanism (standard machines are 3.0kW), hence increasing energy costs by 83%. Under smart capsules, Roche’s ultra-miniature 2026 No. 5 capsule features a pH sensor whose dimensional tolerance specification is ±0.05mm and whose upgrade cost of the detection system is $450,000 / production line.
Environmental and supply conditions adjust sizing possibilities. The shift to No. 2 capsule reduces wasteful packaging space by 28%, the production of 1 billion capsules annually saving 520 tons of PVC material each year to 375 tons, as per EU carbon tax regulation (14 tons of carbon saved per million capsules). However, the 2 mold life of plant capsules (e.g., Vcaps Plus) is just 6 million capsules (gelatin is 12 million capsules), and the replacement frequency is 100% higher. In the new coronavirus epidemic, the shortage of gelatin capsule 0 led to the substitution of pharmaceutical enterprises with HPMC capsule 1, and the revalidation of the process took an average of 5.2 months, and it resulted in an 18% capacity shortage. India’s Dr. Reddy’s reduced the switching cycle to 6 weeks by pre-purchasing a multi-size mold library, yet inventory cost increased by 22%.
Future direction suggests that 3D printing technology will drive the customization of capsules sizes. Merck’s Capsule No. 7 (0.07mL) of 2027 utilizes a microporous structure, where the release of 0.5mg anticancer drugs can be precisely controlled, but the filling accuracy should be as close as ±0.5%, and the equipment transformation cost is more than $600,000. At the same time, the biodegradable capsule must have dimensional stability and expansion rate ≤0.3% in the 75% humidity condition, which promotes the R&D investment of new polymer materials to increase by 34%. The market projects 20 non-standard capsule sizes due to personalized medicine by 2030 but at the cost of overcoming the flexibility of mold, e.g., the price of creating a modular punch system is 40-60% more than traditional alternatives.