From Gelatin to Vegetarian: What Are Pill Capsules Really Made Of?

You are not alone if you have ever wondered what makes up the capsule that holds your medication or supplements. Capsules are marvels of pharmaceutical engineering.  

Beyond being mere enclosures for your vitamins or prescription drugs, capsules determine to a great degree their effectiveness, safety, and appeal. Also, capsules come in different shapes and forms, borne from the interplay of science, patient needs, and ethical considerations.  

The characteristics of capsules are reflected in the materials they are made of, from the traditional gelatin capsules to the modern vegetarian and vegan shells.  

So, in this article, we peel back the layers on pill capsules and explore the various materials they are made of and how they matter to your health.  

General composition of capsules 

Generally, capsules are composed of (1) core materials that serve as their building block and (2) the additives (or adjuvants) that enhance their production and functions.  

The core materials are mainly pharmaceutical-grade ingredients that form uniform gel-like matrices in solution and are amenable to capsule-making. They also have other desirable characteristics like inertness, stability, ease of source, and suitability for mass production. Examples include gelatin, agar, alginate, hydroxypropyl methylcellulose (HMPC), hypromellose phthalate, pullulan, etc.  

Different types of additives are also used in capsule production. These include gelling agents, plasticizers, colorants or opacifiers, lubricants, moisture barriers, disintegrants, preservatives, pH modifiers, antioxidants, flavors, and sweeteners, among others (Check the summary table below for more details on their function and examples).   

As with core materials, capsule additives are also required to be perfectly safe for consumers’ health. Reputable empty capsule manufacturers do adhere to local and international regulatory requirements in choosing and using any of these ingredients. Their selection also depends on the type and function of the capsules being produced. The type of additives chosen influences the final properties of the capsules from appearance to shelf life and dissolution behaviour.  

Gelatin, HPMC, and pullulan are the most common core materials used in commercial capsule manufacture today. We will look at these materials and their capsules in a bit more detail. 

Bovine gelatin and gelatin capsules 

Gelatin is the oldest core material used in commercial capsule production. It is a proteinaceous substance derived from the bones and hides of cattle, pigs, and fish. Gelatin derived from cattle (bovine gelatin) is generally preferred to the porcine and piscine types due to its better acceptability and superior performance in use.   

At Capsuline, we use high-quality pure bovine gelatin to produce our gelatin capsule range.   

Other desirable properties of gelatin as a core ingredient include its good gelling and emulsifying ability, stability, non-reactivity, and glossy appearance.   

As such, gelatin capsules have made remarkable progress as formulation vehicles over the centuries. In 2021, gel caps accounted for 88.5% of the global capsule market.  

Gelatin shells are used in human and veterinary drug delivery for solids, semisolids, oils, and non-aqueous liquid formulations. They are available on the market as either the separable two-piece ‘hard capsules' or the hermetic one-piece “softgels”.   

Typically, producing a gelatin shell requires using only a small range of additives, which contributes to its relatively low-cost production compared to vegetarian capsules. 

Vegetarian capsules 

Changing demands by consumers and advances in capsule technology have caused a recent shift towards vegetarian capsule production.  

For example, consumers with dietary and religious restrictions to animal-based capsules have continuously demanded plant-sourced alternatives. Also, the technological drive – to correct the limitations of gelatin capsules such as their incompatibility with hygroscopic and aqueous formulations, as well as the prospect of specialized drug delivery e.g. targeted delivery – has also contributed to the trend.   

There are many types of vegetarian capsules; however, HPMC and pullulan capsules are the most popular in the vegetarian category.

HPMC and Vegetarian Capsules  

Hydroxypropyl methylcellulose (HMPC), or hypromellose, is a carbohydrate polymer used widely in oral drug delivery systems including tablets and capsules. HPMC has an excellent profile as a capsule core material reflected by the versatility, stability, delivery characteristics, and performance of its capsules on filling equipment. Yet, gelling agents and pH stabilizers are required in the production of HPMC capsules to enhance their stability due to HPMC's sensitivity to pH. 

HPMC capsules have grown in popularity among consumers due to their vegetarian origin. They can be used for hygroscopic, aqueous, and other fills that are incompatible with gel caps, as they do not cross-link with contents. HPMC shells are approved by Kosher and the Vegan Society, and are increasingly favored for drug trials and launch due to their wide acceptability. 

Hence, these capsules have progressively claimed larger portions of the capsule market over the years, especially in the two-piece space. The HPMC market was valued at $359.2 million in 2023 and is expected to double by 2030. 

Pullulan capsules: the new contender 

Pullulan is also a carbohydrate polymer derived from corn starch. It offers a unique alternative to meet the demand for vegetarian shells, offering sustainable eco-friendly options. Its advantages as a capsule core ingredient include its great film-forming ability, non-toxicity, tastelessness, biodegradability, solubility, transparency, and non-mutagenic properties. 

However, it requires the addition of gelling agents to enhance its performance. Also, pulullan cannot be classified as a grain-free product and it is difficult to prove it a Non-GMO, as corn starch is usually extracted from genetically modified corn.  

Yet, pullulan capsules have emerged as a strong contender in the vegetarian capsule sector. They exhibit similar levels of functionality and acceptability as HPMC capsules; although pullulan capsules are often reserved for dry powders, as their high moisture content interacts with absorbent powders and liquid ingredients. Nonetheless, they compensate with an excellent oxygen-resistance property making them the best choice for air-sensitive formulations. 

Bottom line  

It should be noted that consumer demands and technological advancements are bringing up further innovations in capsule production and materials beyond vegetarian requirements. The rise of specialty capsules such as enteric capsules and nanocarriers; techniques such as 3D printing; and increasing ethical and regulatory demands for sustainability may bring more raw materials into capsule manufacturing.  

Overall, the evolution of the materials used in pill capsule production highlights significant developments in pharmaceutical engineering and consumer awareness. Therefore, understanding the materials and processes behind pill capsules can lead to more informed choices and a better appreciation for these small yet significant components of modern medicine.