Gelatin is the traditional gelling agent used to produce softgels. In recent years, different products have progressively emerged on the market based on other alternative polymers such as starch, carrageenan and pectin. Its use, alone or in combination with other gelling agents, conditions the softgel production and modifes the properties of shell cover material, and therefore, the softgel capsules. In addition, the use of new alternative materials such as alginate, pullulan, cellulose and its derivates, PVA, chitosan, gellan gum and agar have been explored and are becoming more important. Their market inclusion has not only led to improvements in terms of compatibility, manufacture, stability, drug release control, cost and sustainability; but also, has enabled to extend the softgel portfolio offering to the consumers friendlier products with vegetal origin. This review provides an updated overview on the alternative options to traditional gelatin shell cover for pharmaceutical and nutraceutical products. Additionally, it evaluates the impact of this change on the shell material behavior over the production and stability of these pharmaceutical forms. This will help to select the best gelling agent, alone or in combination, depending on the defined specifcation during the design and development phase of the softgel product.
1. Introduction
Softgels or soft capsules (SC) are the second more used dosage form for pharmaceutical and nutraceutical products, after tablets. It is a one-piece form based on a shell cover hich contains a wide ariety of hydrophilic and hydrophobic liquid or semi-solid fill matrixes. Many active pharmaceutical ingredients (APIs) and nutrients, alone or in combinations, may be encapsulated together with diferent excipients or additives in solution, emulsion or suspension. In the shell cover, one or more polymers are combined with plasticizer and other optional additives such as colorants, opacifers, favors, sweeteners or preservatives, among others. The shell cover helps to create a “friendly” environment for the active ingredients, protecting them from the external atmosphere,
which is especially important for oils and poorly water-soluble and unstable compounds.[1] Furthermore, the shell flm can modulate the active release profle in specifc locations or at diferent speeds, such as enteric SC hose surface is stable at the acidic pH found in the stomach but breaks down rapidly at the basic pH of the intestine. As ell, SCs have a great acceptance by consumers thanks to ery friendly swallowing capacity, hich is particularly important for oung and old people. Another strong point is the ide ersatility of colors, sizes, and shapes that modify the fnal appearance of capsules playing a strong role on marketing strategies and importantly on consumer diferentiation (Figure 1).
Although SCs have lots of advantages over other dosage forms, there are also challenges and improvement points too. For example, its particular design hich shows two diferent materials – fill and shell can be a particular problem since (1) its direct contact may cause physical and chemical interactions within and between their components; and/or (2) there could be a physical migration of components between the two parts and the external environment, making the SC a ery dynamic system. These phenomena may compromise the integrity of the SC and promote manufacturing and stability issues such as crosslinking, sticking, fragility or blooming issues. In addition, focusing on the SCs based on gelatin, that is the most common polymer used, high sensitivity to the climatic conditions is reported, reducing the shelf-life of these fnished products and/or demanding special storage conditions. Moreover, gelatin has an animal origin, and some consumers demand the use of animal-free materials due to: (1) religion reasons like Islamic and Hinduism, hich do not allow to eat porcine and bovine products, respectively; (2) animal activism that upholds the animal rights and is often against animal exploitation; and/or (3) lifestyles like egetarian and egan diets that do not consume animal meat or any relative animal products, respectively. Last but not least, it is important to emphasize the high cost of SCs production compared to tablets or liquids forms.[2]
These reasons encourage companies to innovate from formulation and production perspectives. On the frst point, the focus has usually been on the fill formulation. There are many studies about the alternatives and improvements of fill formulations in SCs, but the feld of study about shell formulations is less explored and it ofers a large framework of possibilities. In fact, the physicochemical properties of shell cover are critical, having a direct efect on the quality properties of fnal product such as its appearance, release profle and chemical stability of active ingredients encapsulated.[3] Thus, it is necessary to strengthen the knowledge of shell formulations and its potential interactions with the fill materials and the environment to design and develop stable SC products with adequate characteristics.
This review offers a teaching overview on the current “SC world” focusing on the main alternative polymers used to replace gelatin that are already in the market (starch, carrageenan and pectin) or are being evaluated for potential exploitation (alginate, pullulan, cellulose and its derivates, polyvinyl alcohol, chitosan, gellan gum and agar), hich mainly have nonanimal origin obtaining more ecofriendly products with better consumer acceptance. The manufacture of SCs as well as the characterization of their properties are presented in a comparative discussion to understand the diferences that exist between diferent materials. We aim to ofer the readers clear indications to understand hich shell material is the best option for their formulation, manufacture or marketed necessities.
Download the full article as PDF here:
Sustainable Shell Formulations as Alternative to the Conventional Soft Gelatin Capsules in Pharmaceutical and Nutraceutical Applications. A Review.
F. J. Palomero-Hernández, M. Á. Caballo-González, F. J. de la Mata, S. García-Gallego. Sustainable Shell Formulations as Alternative to the Conventional Soft Gelatin Capsules in Pharmaceutical and Nutraceutical Applications. A Review. Macromolecular Materials and Engineering, 2025, 2500003
DOI: 10.1002/mame.202500003
Read also our introduction article on Capsules here:
