In the design of drug dosage forms, the difference between capsule versus tablet is first reflected in production efficiency and cost. Tablets are usually made through a tablet pressing mechanism, with a single device producing 5000-10,000 tablets per minute (such as the Fette 3090 model), while capsule fillers (such as the Bosch GKF 2500) have a speed of about 3,000 tablets per minute. However, the total production cost is 15-20% lower (International Pharmaceutical Technology 2023 data). For example, acetaminophen tablets cost $0.012 to produce as a single tablet, while the equivalent dose capsules cost $0.015, but the latter does not require the addition of disintegrators (saving 8% of raw material costs). According to Grand View Research, the global tablet market will account for 58.7% and capsules for 31.3% in 2022, but the growth rate of capsules in bioavailability sensitive drugs (9.2%) is higher than that of tablets (5.7%).
The release characteristics of the capsule versus tablet directly affect the efficacy. Gelatin capsules dissolve in gastric juices within 15-30 minutes and peak drug concentration (Cmax) is 20-40% faster than tablets (FDA bioequivalence guidelines), for example amoxicillin capsules have a peak blood concentration of 1.2 hours compared to 1.8 hours for tablets. However, enteric-coated tablets (e.g., omeprazole) controlled the gastric release rate to < 5% by PH-sensitive coating, while enteric-coated capsules (e.g., Eudragit L30D-55 coating) required pH≥5.5 to trigger dissolution, and there was no significant difference in ulcer cure rates (94% vs 93%) (New England Journal of Medicine study).
Differences in physical characteristics determine the applicable scenarios. Tablet hardness range 50-200N (such as ibuprofen tablet hardness 120N), can be divided dose but easily due to moisture absorption caused by disintegration time fluctuation ±5 minutes (USP<701> standard). Capsules can be encapsulated in liquid or powder (such as fish oil softgel containing 500mg DHA), and the size adaptability is strong (capsule size 000 1.37ml, capsule size 5 0.13ml), but when the humidity is > 60%RH, the gelatin water content rises to 18%, resulting in a 35% increase in adhesion risk (Drug Development and Industrial Pharmacy experiment). In 2023, Pfizer switched the antifungal voriconazole from tablet to capsule, resulting in a 27% increase in patient compliance (dysphagia complaints decreased from 19% to 3%).
Market and regulation drive innovation differentiation. In the US, 60% of OTC painkillers are tablets (low cost), while in Europe, plant-based capsules (HPMC) will grow to 24% in 2022 due to vegetarian demand (Euromonitor International). Japan requires tablet size ≤21mm (JP18 standard), while capsules (e.g. 00, 23.3mm long) require special approval. In 2021, the FDA approved the first 3D printed tablet Spritam (levetiracetam), with a porosity of > 90% and a 1000mg dose released in 1 second, while ZipDose capsule technology developed by Aprecia has not yet been commercialized.
Stability and storage costs are significantly contrasted. After 6 months of accelerated testing at 25℃/60%RH, the dissolution deviation of tablets is ≤±5% (ICH Q1A standard), while the disintegration time of capsules may be extended to 40 minutes due to gelatin crosslinking (12% over-standard rate). An Indian pharmaceutical company changed the anti-TB drug rifampicin from capsules to tablets, and reduced the shipping breakage rate from 3.7% to 0.9%, saving US $280,000 in annual logistics costs (WHO Procurement report). However, the oxidative degradation rate of fat-soluble drugs (such as vitamin D3) in capsules is 63% lower than that of tablets (Drug Stability Research paper).
The future of capsule versus tablet is being reshaped by technology. Nanocrystalline tablets (such as Merck’s Itraconazole tablets) increase bioavailability from 55% to 85%, while liquid-filled capsules (such as Catalent’s OptiGel) encapsulate macromolecular drugs (such as insulin) and are stable at room temperature for 24 months (28 days for traditional injections). In 2023, Novartis invested $420 million to develop an AI-powered capsule filler that compresses the production error rate of multi-particle sustained-release capsules (including three apis) to ±1.5%, a 40% improvement over traditional process efficiency (McKinsey Automation White Paper).