The tablet and capsule choice relies on drug characteristics and patient needs. From the viewpoint of bioavailability, the overall rate of absorption of capsules is 30% more than tablets due to first-pass effects avoided by them (such as fat-soluble vitamin D3 filled in soft capsules) (FDA 2022 study), whereas tablets are able to lower the fluctuation range of blood concentration to ±15% by employing wet granulations (such as metformin sustained-release tablets), which is better than capsules’ ±25%. As of 2023, based on Pfizer’s data, the tablet production qualification rate (99.5%) is slightly lower than that of capsules (99.2%), since the shell of gelatin can be deformed under the humidity action (≥60% RH), and the scrap rate is 0.3% higher.
Production efficiency and cost vary immensely. The tablet adopts the direct tablet process (e.g., aspirin tablet), single production capacity of 500,000 tablets/hour, cost of one tablet is approximately 0.02 US dollars; The capsule filler machine (e.g., Bosch GKF 2500) speed is only 300,000 capsules/hour, due to the procurement cost of the gelatin shell ($0.015 / capsule) and the filling precision (±3% weight deviation) limitations, cost of one tablet is as much as $0.035. However, capsules may be disintegrated into multiple particles with flexibility (e.g., probiotic pellets), and the dose setting error is ±5%, and the tablet segmenting error is as high as ±20%. According to Novartis’ data of 2021, the ratio of capsule versus tablet development cost is 1.3:1 because capsules need additional package compatibility testing (15% of the total budget).
The patients’ compliance followed a differentiated trend. Swallowing disorder patients and children preferred capsules (63%) since they could be disintegrated to swallow pellets (e.g., omeprazole enteric-coated capsules), while oral collapse tablets (e.g. Zopicone) had a lower taste score (7.2/10) than capsules (8.5/10) although they disintegrated in ≤30 seconds. However, 72% of the market share of elderly chronic diseases belonged to tablets (IQVIA 2023), as aluminum-plastic panel packaging is more convenient than a bottle of capsules, and stability tests show that the main component degradation rate of tablets in hot storage (40°C) is as low as 0.5%/year, while 1.2%/year is for capsules.
Stability and storage conditions dictate the application scenario. Film-coated tablets (such as enteric acrylic resin) will not disintegrate ≥2 hours in the stomach acid environment (pH 1.5), but the gelatin capsule shells will dissolve in 15 minutes under the same environment and lead to premature release of the drug. In 2022, Merck lost $48 million due to the recall of an antibiotic capsule in hot and humid climate (humidity ≥75%); Meanwhile, the use of silica gel desiccant (moisture absorption rate 0.5 g/day) can extend the shelf life to 36 months, and reduce transportation costs by 18%.
New technologies redefine the competitive landscape. 3D printed tablets (such as Aprecia’s ZipDose) are dose adjustable (50-1000 mg), porous ≥90%, but the production rate is 200 tablets/hour; Capsule liquid filling technology (such as CapsCanada’s Licaps) can fill temperature-sensitive drugs (such as insulin) with ≥95% retention rate and production rate of 150,000 capsules/hour. Johnson & Johnson spent $270 million in 2023 on developing nanocrystalline capsules that doubled bioavailability, but were 300% higher in unit cost than usual tablets. Capsule vs. tablet market share worldwide will be 55%-45% by 2028, with tablets retaining the chronic disease market due to cost and stability, and capsules will grow 12% in the biologic medicine and customized therapy market.