Abstract
In 2025–2026, research on softgels focuses concurrently on (i) „greening” and diversifying shell materials (modified starch, carrageenan, pullulan, agar, and other polymers) and evaluating the impact of these changes on material behavior during manufacturing and product stability.[1] A second strong direction is the development of lipid-based and self-emulsifying formulations (SNEDDS) specifically designed for softgel filling to address the low aqueous solubility and variable bioavailability of many drug candidates.[2] Concurrently, there is increasing emphasis on process engineering and technology selection (e.g., seamless capsule manufacturing by the droplet method vs. spray-drying microencapsulation) depending on the active ingredient type, required scale, and storage conditions.[3] An important quality trend is the modeling of shell stability and the „leakage” phenomenon as a function of moisture absorption, along with predicting mechanical failure time using Arrhenius and generalized Eyring models, which aims to shorten shelf-life evaluation from months to a few days of research.[4]
Innovations in Capsule Shell Materials
Research and reviews from 2025 show that the market and literature are systematically shifting towards alternative shells to classic gelatin, including systems based on starch, carrageenan, and pectin, as well as alginates, pullulan, cellulose derivatives, PVA, chitosan, gellan gum, and agar, with these alternatives potentially considered as single gelling agents or in combinations.[1] This trend is described as beneficial not only from a „plant-based origin” perspective but also in terms of compatibility, manufacturability, stability, and release control, as well as cost and sustainability.[1]
Modified Pea Starch as a Plant-Based Shell
A 2026 report showed that modified pea starch-based shells (starch/carrageenan premix, LYCAGEL®) can be manufactured on standard softgel equipment alongside gelatin shells, and the resulting capsules exhibit „similar performance” with concurrently higher stability against environmental stress (heat, moisture).[5] In stability tests, a decrease in hardness was reported, among other things, after 3 months of storage in blisters for both gelatin and starch capsules, with a stronger effect under 40°C/75% RH conditions.[5] Simultaneously, the disintegration of gelatin capsules was <5 min under the tested conditions, while starch capsules did not exceed 10 min (and additionally shortened in blisters at 40°C/75% RH).[5] In bottles at 40°C/75% RH, the hardness of gelatin capsules could not be measured due to melting/deformation and sticking, whereas starch capsules remained measurable, which is a practically significant sign of process-logistic resilience in higher humidity/temperature.[5]
A key design conclusion from this source is the impact of packaging and moisture barrier: water content in the shell increased during stability for all capsules, more in blisters than in bottles, and more at 40°C/75% RH than at 25°C/60% RH. The authors emphasize the need to select packaging with an adequate moisture barrier for both gelatin and starch (LYCAGEL®) capsules.[5] Concurrently, the material indicates that the industry is seeking vegetarian alternatives with „similar or higher” technical efficiency compared to gelatin, manufacturable on standard equipment and at „full speed,” with additional options for filling materials and better stability.[5]
Carrageenan as a Gelatin Substitute
A 2025 review indicates that iota-carrageenan (from red algae) is considered more suitable for softgels than kappa-carrageenan due to its ability to form flexible, elastic gels, which is critical for the mechanical integrity of the shell during processing, storage, and administration.[6] The same review, however, highlights technological challenges for iota-carrageenan in softgel shells, including low solubility, high viscosity, and slower disintegration compared to gelatin.[6] Strategies for improvement included structural modifications (fermentation or depolymerization), the use of plasticizers, and blending with other polymers (e.g., modified starch) to enhance the mechanical and functional properties of carrageenan films.[6] The authors conclude that, after optimization of formulation and process, carrageenan has potential as a halal, environmentally friendly, and competitive material, and carrageenan shells can achieve properties comparable to commercial softgel shells.[6]
Additionally, an experimental work from July 2025 on „seaweed” shells based on kappa-carrageenan showed that the choice of disintegrant significantly modulates the disintegration mechanism (wicking vs. swelling) and allows for targeted improvement of disintegration/swelling parameters in plant-based systems.[7] In particular, Primogel exhibited the lowest swelling degree (949.944%) and the fastest disintegration (36 min 21 s), while NaCMC and PVP resulted in longer disintegration times of 47 min 02 s and 48 min 26 s, respectively (none of the formulations achieved the <30 min goal).[7] The authors attribute these differences to the wicking mechanism for Primogel, and SEM analysis revealed structural differences (e.g., large granules for Primogel vs. smoother surfaces for PVP), which supports the approach of „microstructure engineering” of plant-based shells through additive selection.[7]
The table below numerically synthesizes selected results for alternative shells, directly useful for R&D benchmarking.
Formulations and Bioavailability
In 2026, reviews dedicated to SNEDDS in softgels describe them as a formulation strategy enabling the creation of fine oil-in-water nanoemulsions upon gentle mixing in gastrointestinal fluids, aiming to address the barrier of low aqueous solubility and the resulting low and variable bioavailability of many new drug candidates.[2] These reviews emphasize that the incorporation of SNEDDS into softgels can enhance dosage accuracy, improve patient acceptance, and protect labile substances, which stems from the nature of the capsule form and its „closed” environment for lipidic formulations.[2]
From a qualitative perspective, review articles direct the development of SNEDDS „for softgels” toward principles of excipient selection and critical quality attributes, as well as physicochemical characterization and in vitro and in vivo studies interpreted in the context of fill-shell compatibility, stability, and biopharmaceutical behavior.[2] Concurrently, practical limitations and risks specific to softgels were highlighted, including fill-shell interactions, risk of precipitation upon dilution, and long-term stability concerns, with a parallel indication of development directions such as supersaturable systems, innovations in lipid excipients, and approaches to predictive in vitro–in vivo correlation (IVIVC).[2]
From the perspective of manufacturing transfer, a full-text review (published February 15, 2026) directly addresses industrial scale-up challenges and regulatory expectations for SNEDDS products filled into gelatin capsules, which significantly shifts the discussion from „formulation itself” to the area of CMC and quality control throughout the product lifecycle.[8]
Manufacturing Processes and Quality Control
Selection of Capsule Manufacturing Technology
A 2025 publication compares two primary technologies for manufacturing seamless gelatin capsules: the droplet (coaxial) method and spray-drying microencapsulation, describing the design features of the devices and key process parameters (including capsule size/shape, shell composition, dosing accuracy, and productivity).[3] Conclusions from the analysis (based on technical documentation, publications, and pharmacopoeial standards USP/EP) indicate that the droplet method is associated with high dosing accuracy and an attractive appearance of large spherical capsules with a liquid core, while spray-drying enables mass production of microcapsules for bulk mixtures and maintaining the stability of sensitive ingredients.[3] The authors emphasize that technology selection should depend on the active ingredient type, required scale, and storage conditions, and also point to possible future improvements, such as new shell materials and milder drying regimes.[3]
Prediction of Stability and Leakage Phenomenon
A study from July 2, 2025, proposes a method for estimating the „leakage” stability of gelatin softgel shells during storage, combining a description of moisture absorption with a prediction of time to mechanical failure.[4] The authors report that the leakage phenomenon primarily results from gelatin swelling after water penetration, rather than chemical changes, which was confirmed by FTIR and SEM observations (no appearance of new structures / disappearance of original structures and changes in morphology after moisture absorption).[4] The Arrhenius equation for the temperature dependence of the moisture adsorption coefficient (e.g., and ) was introduced into the modeling.[4]
In the mechanical section, a generalized Eyring model was applied to estimate failure time (in puncture and tensile tests), achieving agreement with experiments at a relative error level of 4.0% (puncture) and 3.1% (tensile).[4] For example, under conditions of 30°C and 92.31% RH, the failure time in the puncture test was 7.29 h (measured) versus 7.00 h (estimated), and in the tensile test, 9.54 h (measured) versus 9.84 h (estimated).[4] From the perspective of quality control and accelerated product development, the authors emphasize that shelf life can be estimated in „a few days” of experiments with this approach, whereas traditional accelerated and long-term tests usually require 6–12 months, which can shorten the decision cycle in R&D and facilitate future quality prediction.[4]
Therapeutic and Nutraceutical Applications
In the application area, a 2025 work describes the development and evaluation of gelatin capsules with an ethanol extract of Terminalia chebula, indicating the purpose of use as support for „nutritional deficiencies” and general dietary well-being, while simultaneously requiring compliance with pharmacopoeial standards regarding stability, uniformity, and quality.[9] The authors report a preformulation approach encompassing the evaluation of physical properties, solubility profile, and parameters such as loss on drying and sulfated ash, followed by the formulation of the shell (gelatin, glycerol, purified water) and a fill containing the extract with hydrogenated vegetable oil, soy lecithin, soybean oil, and beeswax.[9] The scope of post-manufacturing evaluation included, among other things, permeability and leak tests, as well as assays for potency, dose unit uniformity and content, disintegration time, moisture level, and microbiological limits, which reflects the practical quality control requirements for products with plant extracts.[9]
Consequently, the authors indicate that among the prepared batches, combination F4 (fill) and F2 (shell) were selected as having better quality under given storage conditions, with assay values maintained within limits. The capsules were characterized by a uniform appearance, consistent fill weight, appropriate hardness, and acceptable disintegration.[9] The authors conclude that stable, high-quality softgels with T. chebula extract were obtained, and the formulation protected the active substance from degradation and ensured consistent API delivery, which is a typical functional argument for softgels in the nutraceutical and phytopharmaceutical segments.[9]
Future Directions and Conclusions
In the area of shells, the collected sources from 2025–2026 indicate a practically oriented transition from „material alternatives” to „property engineering”: the selection of polymer (e.g., starch/carrageenan) and additives (e.g., disintegrants) is combined with measurable parameters such as disintegration, swelling, hardness, and moisture absorption, as well as with the selection of packaging providing a moisture barrier.[1, 5, 7] In particular, data on the increase in shell moisture and property degradation under 40°C/75% RH conditions strengthen the hypothesis that for softgels (both gelatin and plant-based), packaging is an element of „extended formulation,” not solely a logistical component.[5]
In the area of formulations, SNEDDS reviews directly link the design of the lipid system with shell–fill compatibility, as well as with the risk of precipitation and long-term stability, which shifts the focus to critical quality attributes and risk reduction strategies at industrial scale and in regulatory expectations.[2, 8] From the perspective of process and quality, 2025 works show that softgel technology development includes both the selection of the „process family” (droplet vs. spray-drying) based on product requirements, and the development of predictive models that can quantitatively forecast shell failure (leakage) as a function of temperature and humidity, potentially shortening the shelf-life evaluation time in R&D.[3, 4]
From an implementation perspective, the most „industrially ready” solutions in the presented sources are those that simultaneously: (i) operate on standard softgel equipment, (ii) have documented behavior under stability conditions and in various packaging systems, and (iii) are embedded within quality control and risk modeling frameworks (shell–fill interactions, moisture absorption, leakage).[2, 4, 5]
