capsule size comparison is motivated by a number of factors such as drug formulation characteristics, equipment used for production, and regulatory requirements. For instance, when employing the commonly used capsule No. 000 to No.4, 1.37mL No. 000 is suitable for light powder with a density of ≤0.4g/cm³ (micro-pulverized API etc.), while only 0.20mL No. 4 is being utilized, requesting dense active ingredients with the density of ≥0.8g/cm³ (pre-gummed starch composite particles etc.). Pfizer’s 2023 research revealed that the alteration of ibuprofen granules from capsule 1 (0.50mL) to capsule 2 (0.37mL) raised the filling rate from 2,200 to 3,000 granules per minute but resulted in the grinding of the API particle size from 180μm to 75μm to ensure dissolution (Q30≥85%). Consequently, the brittleness test failure rate rose from 0.5% to 2.1%. The European Pharmacopoeia indicates that the capsule filling fault should be ≤±5%. If capsule No.3 (0.30mL) holds 0.28g drug, the bulk density variation greater than 0.05g/cm³ will cause the weight variation greater than 7%, triggering the production batch scrap risk, which will create a loss of 1.2 million US dollars when the annual production volume is 100 million capsules.
Production equipment parameters directly influence capsule size comparison. The Bosch GKF 2500 German model accommodates the 000 to 1 capsule switch, and this takes 45 minutes (mold cleaning and calibration included), whereas the expansion of the GKF 2700 to 4 capsule comes with an additional investment of $120,000 module, but the filling qualification level has been increased from 97.6% to 99.3%, and the annual waste reduction has increased to 1.8 tons. The price difference of capsule shell is astonishing: the unit price of gelatin capsule 0 is US $0.028 / capsule, 86.7% higher than that of gelatin capsule 4 (US $0.015), but when filling the same API, the filling efficiency of capsule 0 is 32% higher than that of capsule 4, and the yearly consumption of coating material can be reduced by 15%. According to the case of Novartis in 2024, when the hypertensive medication was reformulated from No. 00 to No. 1 capsule, while raw material cost increased by 18% (since more flow AIDS had to be added), logistics cost decreased by 23% (120,000 more capsules in a container), and the overall annual savings are $540,000. Apart from that, United States FDA 2025’s new regulation stipulates capsule size labeling precision of ±0.1mm, so the detection system is enhanced, such as Thermo Fisher VisionPro 3D detector size variation rate was enhanced from 92% to 99.8% and the cost of equipment increased by $350,000.
Regulatory and market pressures drive technology upgrading. USP<1151> required the capsule to disintegrate in 30 minutes in the pH1.2 medium, and the RSD value of capsule No.2 dissolution curve (3.8%) was clearly lower than that of capsule No. 4 (6.5%), especially in the sustained release preparation, the difference was widened to 9.2%. The PMDA 2025 regulation of Japan reduced capsule size tolerance from ±0.25mm to ±0.15mm, raising the capsule 00 scrap rate from 5% to 12%, but convenience survey of capsule 00, the patient swallowing reported that capsule 4 (92%) acceptance was 21% higher than capsule 0 (76%). Environmental factors cannot be ignored: capsule 2 can reduce the level of an individual bubble cap by 28%, according to year-to-year production of 500 million capsules, annual PVC material consumption from 380 tons to 274 tons, in accordance with carbon saving objectives under the European Union’s 2023 Green Pharmaceutical Agreement (12 tons of CO₂ equivalent saved per million capsules). In addition to this, there is also new smart capsule technology driving dimensional innovation: Roche developed capsule No.5 (0.15mL) in 2026 with onboard micro sensors to monitor pH levels of stomach acid and trigger drug release, but filling accuracy needs to be improved from ±5% to ±1.5%, and equipment conversion cost reaches up to $800,000 / production line.
Resilience in the supply chain is a new aspect to watch out for. In the recent coronavirus epidemic, the global shortage of capsule 0 has forced pharma manufacturers to change to capsule 1, but the specifications have to be re-validated, which takes 6-8 months on average, resulting in 15-20% capacity loss.
India’s Dr. Reddy’s Lab reduced the switching period to 45 days by pre-purchasing multi-size mold stock but increased storage costs by 18%. Furthermore, plant capsules (HPMC) dimensional stability is better than that of gelatin, and expansion rate is only 0.8% for 75% humidity (3.2% for gelatin), so the market share of plant capsules 2 in tropical regions rose from 12% in 2019 to 41% in 2025. At the same time, the plant capsule mold wear rate is 30% higher than gelatin, with a punch rod having to be replaced with every 10 million pieces made (with a replacement cost of $24,000), whereas the life of the gelatin mold can be up to 25 million pieces.
Finally, clinical needs result in innovation in market segments. Pediatrics tend to use capsule No. 4 (92% success in swallowing), but the API concentration needs to be increased to above 80%, which may cause the problem of dissolution lag. Johnson & Johnson’s segment-type capsule No. 3, developed in 2024, integrates rapid release + slow release with double-layer filling technology, and has a ±3% difference in loading, but the production speed is reduced to 1,800 capsules/minute (3,500 capsules for standard models). More often in animal medicine, capsule 00 is preferred because it can fill large size particles of veterinary antibiotics (≤1,200μm particle size), but it needs to be equipped with a special vibration filling system (power requirement enhanced from 2.2kW to 5.5kW), and energy expense enhanced by 120%.