The Half Decent Pharmaceutical Chemistry Blog

In a city where nearly everything revolves around the university, this is a period of the year when it could be really hard to find people to hang out in a pub with for a couple of refreshing pints. Friday night before Easter is, apparently, a lonely one when your so-called best friend is catholic (much more than what you ever thought).
To sum up, yesterday I faced the dilemma of whether to spend the night staring at a computer or to go out on my own. Actually, there was no dilemma at all, as I have always had wonderful times at pub counters. Especially when rough and full of depressed members of the lower-classes.

While sitting at the centre of one of these naturalistic paintings, unwinding in the dim light and finally reconsidering all the things that had happened to me in the last ten days, I began to reconsider an idea one of my colleagues at the chemist’s gave: the World’s Biggest Rectal Suppository ever made! This really could have been an ambitious but gratifying target for a pharmacy and, because we were in a small town, something the locals could have been proud of for the years to come, a tale grandparents would bring out to entertain children.
And, who knows, an attraction for tourists: Visit the land of the Massive Suppository!

I know suppositories are a laughing stuff, but to make them is far from being trivial: there is actually much more science involved than you might expect. It is so complicated that, despite the cheap ingredients, rectal suppositories are being quickly dismissed as means of administration. Compliance is another issue, but not so fast on that front. Just take oral administration, which has rapidly taken over old rectal formulations because of superior compliance: despite the unquestionable user-friendliness of introducing the drug through the right orifice, you can’t think about administering anything through the oral route to an unconscious person, while you could rely on rectal suppositories. What’s more, even in less dire conditions, nausea might make ingestion of oral tablets impossible: therefore, a suppository is just what you need.
When embarking on an ambitious project such as crafting an immense rectal suppository, compliance is obviously not an issue. What could be annoying, on the other hand, is the fragile equilibriums taking place in this type of formulation, which result in them being a lab-course exercise only these days.
When you design a suppository you cannot but start with the environment where it will be absorbed. The rectum is rich in mucous: therefore, hydrophilic excipients such as PEGs or glycogelatin are, theoretically, excellent solutions, dissolving easily and releasing the active ingredients. PEGs are, indeed, fantastic: they give you the opportunity to try incredibly concentrated formulations, highly recommended when defecation is to be promoted (increasing osmotic pressure leads to rectal irritation).
However, if absorption and systemic effects are required, instead of a banal local effect, only lipophilic active substances could be introduced into the aforementioned hydrophilic suppository, as a double partition equilibrium takes place: one between the drug and the mucous (hydrophilic) and the other between the mucous and the mucous membrane.
To sum up, the content and the excipients must have opposite partition coefficients to yield a systemic effect, following a decent absorption.

The same goes for hydrophilic active ingredients, generally expected to reach the blood stream and, thus, frequently combined with lipophilic substances such as triglycerides or, more often, cocoa butter. The latter is the traditional excipients for rectal suppositories, as it’s incredibly cheap and certainly not smelly. These suppositories must melt in the rectum, where the average temperature is 37°C, yielding a huge, oil bubble, through which a partition equilibrium is in place.
However, the main problem with cocoa butter is its polymorphism: there are up to 4 different types of crystals, covering a range of melting temperature from 17°C to 37°C. In particular, the desired 37°C crystal is also the most stable of the lot, but, upon overheating of the mixture to get the water in oil emulsion that we will solidify in our casting mould, a conversion to a less stable form occurs: this form is characterised by an awfully low melting point (26°C), which ruins the whole product, making it unsuitable for the job.
This problem, as every good technician knows, is worsened by freezing point depression of cocoa butter when it gets mixed with the active ingredients, which makes preventing overheating an even tougher task.
Have a nice Easter (whatever your religion).