All4Nutra
We all know that medicines are often tablets and capsules right? But what are they, how do they work and how are they made? In this video PharmaDrama aka Prof. Simon Gaisford looks at the formulation of hard-shell pharmaceutical capsules.
See the video:
and read the transcript:
Welcome to Pharma Drama, the channel where we look at the science of healthcare and healthcare products. In this video I’m going look at a very common type of medicine – capsules. What they are, how they are made and how they work. So, if that sounds good to you, get yourself a drink – I’ve got… ah coffee – and let’s make a start.
After tablets, capsules are the second most common type of dosage form and I am sure you will be familiar with them. If you’ve watched the video on tablets, and if you haven’t I have put a link below, then you’ll know they were patented by a Brit, in 1843. Capsules, on the other hand, were patented slightly earlier, in 1834, in France by a Parisian pharmacist called Joseph Gerard Dublanc, who encapsulated drugs in one-piece gelatin shells. Today we would call these soft-gel capsules, and they are generally used to encapsulate liquid formulations, so are marketed as fast-acting. We will look at soft-gel capsules in a separate video.
The most common type of capsule design are two-piece, hard-shell capsules. These are designed to encapsulate powders and were first patented by another Brit, James Murdoch, in 1847. The School of Pharmacy, where I work, was founded in 1842 by the Royal Pharmaceutical Society of Great Britain and I like to think that the patenting of tablets (in 1843) and capsules (in 1847) is a reflection of our inspiring teaching… Anyway, hard shell capsules have two pieces that lock together and they are filled with whatever drug powder needs to be delivered. The narrower diameter part is called the body and is the part that contains the powder or granules. The wider diameter part is called the cap and is the part that keeps the capsule’s contents in place.
Hard shell capsules have many advantages over tablets and other oral formulations. From a manufacturing perspective, since capsules contain the drug powder directly there is no need to compact it into a tablet and hence no need for excipients to help make the powder compress. Any drug powder can be simply poured into the shell and because of this capsules are often used by pharmacists when they are preparing medicines directly for patients; the pharmacist can weigh drug powder into capsules directly for individual patients (we call this extemporaneous preparation or, if you are American, compounding). Colourants can be added to the shell which enables the capsules to be made in various colours helping with appearance, branding and identification. In particular, capsules are commonly produced in two-colour combinations; if a patient is taking multiple drugs per day then colouring capsules differently makes it very easy to identify the different medicines. Capsules can also be film-coated, giving them a smooth and shiny appearance, and can be printed on directly.
From a patient’s perspective capsules look and feel the same – being oval and smooth to the touch, they are easy to swallow with water. The capsule shell is readily soluble in water, and so once in the stomach capsules will dissolve in a few minutes to release their contents. Since the drug they contain is inside the shell, capsules also keep the drug away from the mouth and so mask any unpleasant tastes (nearly all drugs taste extremely bitter) or odours. And finally, if a patient finds them difficult to swallow, capsules can be opened up and their contents dispersed in a drink or sprinkled on food (although this means the formulation no longer provides any taste-masking).
Capsule shells were originally made with gelatin, and many still are. Gelatin is made up of proteins and it is an excellent material for making capsule shells – it is non-toxic and forms films easily with good mechanical strength and shine. It is also readily soluble in water. However, because gelatin is derived from animals, there has been a drive to replace it with a plant-based alternative. Usually a cellulosic polymer is used, typically hydroxypropylmethyl cellulose (HPMC or hypromellose). Like gelatin, HPMC has been used for many years in pharmaceutical products and it is non-toxic (it is classified as a Generally Regarded as Safe, or GRAS, excipient by the regulators). If you want to know more about gelatin, HPMC or indeed any other pharmaceutical excipients, then I suggest heading over to the PharmaExcipients website, which contains masses of information (there is a link in the description below).
Films made from gelatin and HPMC both contain water – the water helps make the films soft and malleable. Gelatin films generally contain around 15% water while HPMC films contain around 6% water. This has a consequence for the stability of the capsules however; the higher water content of gelatin films means there is more chance of water interacting with the contents of the capsule – water can degrade drugs via hydrolysis. Also, water has a plasticising effect – making the film more malleable – so if water if lost on storage a film can become brittle. Since gelatin films contain more water, they are more plasticised than HPMC films and so are more at risk of becoming brittle upon storage.
Irrespective of what polymer is used, capsule shells are made by a dipping process. Metal moulds (called pins) are dipped into a heated solution of the polymer. The solution can contain other excipients too, such as colourants. Because the pins are cold, the polymer forms a film on the pins. Once the film is thick enough the pins are removed and the film is dried in an oven until the desired water content is reached. Two sizes of pins are used – one for the body and one for the cap.
Capsules are filled with powders using capsule-filling machines. The two parts of the capsule are separated, the body is filled with powder or granules and the cap is put back on. To facilitate filling, the body and cap have grooves and dimples on. These are designed to interlock, which is how the cap locks onto the body. Usually there are also small air vents – these are designed to allow air to escape from the cap as it is placed over the body. This is very important, especially on high-speed filling machines, as otherwise a positive pressure would build up inside the capsule during filling that would blow the cap back off!
Capsules come in different sizes, depending on the volume of powder that needs to be delivered. Somewhat confusingly, the smaller the number of the capsule, the larger the volume it contains! The smallest capsule, size 5, has a volume of 0.13 millilitres while the largest, size 000, has a volume of 1.36 millilitres (I should note here that larger capsules are available, but they are not generally used for oral delivery to humans). The volume refers to the body of the capsule (the part that is actually filled with powder).
Capsules can be filled with powders, granules, pellets, microparticles and, indeed, almost anything else you can think of. Other than liquids though – they tend to dissolve the capsule shell and so are put into softgel capsules, as we will look at in a separate video. This versatility means capsules are really good early in the development process of a medicine when almost anything can be dosed into them.
One other thing to note is that while gelatin and HPMC capsules readily dissolve in water, and so make excellent immediate-release dosage forms, it is possible to formulate capsules in a way that makes them dissolve more slowly. This can be done by using a different polymer from HPMC or by coating the capsule with a polymer film. The film is made from a polymer that is insoluble at low pH and becomes soluble at higher pH. Because the pH increases along the GI tract, this keeps the capsule from dissolving until it reaches a particular section. We call these films enteric coats. There are lots of polymers that can be used to make enteric coats and again if you are interested in them I highly recommend the Pharma Excipients website!
Right, that’s the basics of hard-shell capsules covered. Hard-shell capsules have two pieces, the body and the cap, that are made from gelatin or HPMC and snap together. The body holds the drug powder and the cap keeps everything in place. Capsules can be used to deliver any sort of solid formulation and they are available in a range of sizes. Liquids are delivered in softgel capsules as we shall explore in another video. If you found that useful please hit the like button and consider subscribing – it really helps the channel. Otherwise, thank you so much for watching, and I’ll see you again soon.
See our background article on binder excipients:
