The Half Decent Pharmaceutical Chemistry Blog

Whenever I think about olive oil (not very often, if you were wondering) I always link it to Renaissance. In my mind, to be precise, oil extraction makes me visualise the image of a Renaissance court: people wearing elaborate and uncomfortable (for the job in hand) clothes making a medieval, group dance while working with a 15th century grinder, with its traditional heavy grindstone.

To complete the picture, I also imagine the tune guiding the dancers/workers throughout the extraction: a music which is pretty famous here in Italy (well-known for olive oil and, moreover, Renaissance courts), because it was the jingle of an old TV programme.
Play it while reading: it’s worth it.
Although olive oil is now a massively utilized ingredient in cosmetics, it’s rather uncommon to find it in prescribed galenic preparations. When it comes to ointments, physicians tend to indicate less expensive oils.

Happily, however, this week I’ve had the opportunity to realize how helpful olive oil could be in the making of salves containing vicious zinc oxide. Last time I met it was for an incredibly dense ointment that, to make things worse, was required in large quantity.
This time, on the contrary, the final weight was ridiculously low: only 100 g. Besides, the prescription immediately revealed I wouldn’t have a hard time, as it said: “Zinc Oxide 50 g, Olive Oil 50 g”.

For the very first time, thus, the problem was that the salve would have been much closer to a liquid emulsion or suspension rather than to any solid preparation. One way to deal with the problem could have been to simply pour the oil in the beaker with all the zinc oxide and start mixing the two components but this approach, apparently, lead to clots formation, no matter how long or vigorously you stir. Or, at least, you would oddly spend an huge amount of time stirring it with few chances of eventually yielding a decent result.

So, I worked as usual, using marble platform and spatulas, but, in this case, dropping all the powder first and then adding little by little the oil, carefully stirring in the two components especially towards the end, when the oil was being absorbed slowly and the liquid tent to go everywhere
In the end, though, the fluidity of the salve proved to be a bit of an issue when it was time to transfer it from the platform to the plastic vase, with the last bit that had to be literally trickled in.
Still, although much more expensive than other oils generally employed for these purposes, olive oil undoubtedly makes preparation incredibly easy, quick and, more importantly, is anallergic, which might explain why it was chosen by the physician, and terribly effective for treating minor skin problems such as dry skin or sunburns.

Did Louis XIV suffer from acne? Was his heir subject to recurrent episodes of impetigo in his childhood? Does Staphylococcus aureus have huge problems with French? These are some (pointless) questions that popped into my mind a few days ago when, at the chemist’s, I was told to prepare a solution whose name, like everything in French, sounds like a perfume: eau de Dalibour.

This galenic preparation is named after its inventor, Monsieur Jacques Dalibour, surgeon general of the French army under Louis XIV. While not busy on a battlefield, however, monsieur Dalibour spent time in his laboratory working at his remedies (this very preparation, for instance, can be made as an ointment varying the excipients but leaving unaltered the active substances), which are still pretty popular in France.

L’eau de Dalibour is an astringent and is topically administered to treat either acne and impetigo, which, in case you didn’t know, is just another, sophisticated name for school sores. Obviously, in the pre-antibiotics era, it was used on its own, while, nowadays, it remains a very reliable coadjutant to oral antibiotics, which helps relieve local pain. However, mild forms of impetigo are apparently still treated with Dalibour remedies.

These drugs may be a must for all those weird people who think antibiotics, as well as any synthesised molecule, are evil. L’eau de Dalibour, in fact, contains only natural (whatever that means) compounds: zinc and copper sulphate (both present in minerals, so, I guess we can say they’re natural), saffron tincture (very exotic), camphor and water. Mind you, at least they’re much better than Bach Flowers, hypnosis or homeopathy.
To work by the book you should stick to this recipe: copper sulphate 1g, zinc sulphate 3.5 g, saffron tincture 0.1g, camphor 0.1 g and enough water to reach a final weight of 100 g (ingredients for galenic preparations are often given in weights even when solutions: this simplifies the calculations for the price, as the tables are all in euro/gram).

Unfortunately, we didn’t have any saffron (not to mention its tincture) and, although I tried to convince the pharmacist who usually look after the lab that we could buy saffron at the market and I was willing to prepare the tincture, she said it was a stupid way of wasting time: let’s just forget about saffron and use only an alcoholic solution of camphor, adding it to the aqueous solution of the sulphates until camphor begins to precipitate. Very accurate.
Then, filter the lovely, pale blue solution and that’s it.
It is appalling, in my opinion, to work this way: monsieur Dalibour would have never thought to save time just because an exotic ingredient was missing or (because she felt the need to add another reason to support her silly decision) claim the blue colour had to be preserved and saffron would have turned the whole solution into a weird, different colour. That’s just another reason why don’t fancy the idea of working at a chemist’s for the rest of my life.
Anyhow, I’m there just because I have to and, so, I followed the instructions and (quickly, indeed) prepared a beautiful blue, Dalibour solution.

Once upon a time, pharmacists were absolutely proper chemists. They sold substances to cure but, at the same time, they also handled extremely poisonous stuff: the line between pain-killer and killer poison was even more subtle than today.

A pharmacists didn’t handle smart boxes either: huge bottles and vases filled with powders were on the shelves behind the counter, usually covered by a two-plates balance and massive books, and he (because in the past there weren’t female pharmacists) had to prepare anything by himself.

Still, at least in Italy, even nowadays making galenic preparations gives you the opportunity to work as in the glorious days, but, unfortunately, there is something that is slowly but constantly becoming so old-fashioned that even students don’t do anymore. This is the old art of folding powders in dose bags.

One of reasons dose bags are dying out is due to the extremely simplicity of filling capsules: even if you need a small quantity of a substance in each unit, you can fill the rest of the volume with some inactive powder. Not only are capsules easier to make, but the customer will buy something which looks exactly like an industrial product and this, apparently, increases dramatically compliance.

Capsule-making is also much faster than preparing dose bags. 100 capsules are opened, filled and closed at the same time, while you have to weigh the content of EACH dose bag and then you prepare EACH one separately.

So, there you are: dose bags are painfully slow to prepare for the pharmacist but also less practical and good-looking than capsules for patients.

Seldom, however, they are a reliable option: for example, if you need less than 100 or 50 units or, as happened last week, a mother has to administer an oral antibiotic to a baby, who, predictably, can’t swallow tablets or capsules.
So, we decided the only way she could solve such a delicate issue was to pulverize the tablets in a mortar and then equally distribute (spending ages weighing everything) the resulting powder in 27 dose bags.

So, I’ve decided to let images speak for themselves and here is a series of pictures to show (step-by-step) how to make dose bags, using glassine paper (the common weighing paper).

For what concerns the second picture, it must be pointed out that the red arrows indicate you must fold up the paper irregularly, so that, in the end, you will have a smaller bit of weighing paper to fold into the other larger end.
In the end make sure you’ve closed each bag perfectly, shaking them on your hand: no speck of powder must come out.

Now, enjoy yourself with handmade glassine paper dose bags: do not let this ancient art die! 

The answer to this huge question isn’t blowing in the wind, friend, but it’s locked inside these capsules.

As for cancer,  prevention is everything and, when it comes to flu, people look instinctively  at vitamin C. So, to show you how a manual capsule filling system works, I’ve chosen the making of a nice set of 100 capsules of ascorbic acid.

If my prediction is right, giving such a detailed description of how to prepare this kind of drug will cause the following results: the wise people will immediately contact a massive Chinese supplier and make an enormous order of this material before its price gets astronomic, once bird flu will have hit the Eastern world, of course. Number two: the aforementioned wise people will instantly cease whatever activity they were involved in and begin to live clandestinely, mass-producing these capsules and giving them for free for the benefit of mankind, while the governments (predictably corrupted by pharma companies) will try to arrest them.

Hmm, well, at least I’ve given you the idea for a novel or a film, haven’t I?

Ok, whatever you want to do with capsules, thing is they are incredibly easy to prepare. All you need, apart from the powder you’ll load them with, are the empty capsules (cheap) and the capsule filling machine. As you can see, the latter is rather simple and costs less than 15 €.
Let’s say you prepare 100 capsules of vitamin C, each containing approximately 0.5 mg. Certainly this quantity isn’t enough to completely charge them, so, plainly, you have to add a filler (such as spray-dried lactose).
To calculate how much of this filler it’s required, you place all the ascorbic acid in a graduated cylinder and add filler powder until you reach the required volume.
Finally you mix the two.
Meanwhile you place the capsules in the machine: to avoid contact with your dirty, wet hands, that would ruin the structural integrity of the gelatine envelop, you can use an “automatic charger": this useful thing allows you to charge the filling machine loading 50 empty capsules, placing them randomly (as shown) and then, pressing a button on a side, making them slide down in the holes in such a way that the long and slim halves goes down.
Sometimes, unfortunately, something goes wrong and you can see a capsule or two are oriented incorrectly, but that’s just “bad” luck: you remove the wrong ones and manually put them in the right way.

Since you load 50 capsules, you repeat the procedure, thanks to the two holes the loader can be plugged into that are present on the filling machine.

Time to open: two screws are regulated so that they block the bottom halves. At this point you close the upper glass, grab the upper part of the machine and quickly pull it.
Oooo! Nice!
Release the bottom layer: everything will slip down, revealing a sort of slide in the plastic layer that helps you to fill. This operation is carried out using a sort of thick, plastic card. Yeah, like a cocaine pusher.
Once all the powder has gone into the capsules, you place the upper part back on the machine. This is the tricky part: you must grab all putting your thumbs on top and you other fingers under the machine. Carefully you lift the bottom layer and “feel” the two-halves touching.
As you realise they match perfectly, you pull the said layer very rapidly: it’s easier to do than to describe, by the way.

If you were right and the halves really matched, you’ll instantly see the capsules “suspended” in a remarkably neat way. Otherwise you need more practice, lad, because your capsules have just crushed into each other, instead of being closed…
Now you can start your own illegal business! Enjoy!

Monday, September 3. Afternoon. On the “to do” list there’s only one prescription to prepare: a mouthwash. Anything difficult or interesting? Not at all: 4% sodium borate aqueous solution.

A borax mouthwash is a common coadjutant therapy to treat oral infections by fungi, with sodium borate particularly helpful for teeth. Obviously, no alcohol must be present in such a preparation or the situation will worsen.
Mind you, these days it’s pretty hard to find alcohol in any mouthwash, unlike the early ones which were often welcomed by dire alcoholics with severe withdrawal syndromes.

The prescription didn’t even say how many millilitres I was supposed to make. So, the most exiting moment was when TWO assistants (after some sort of stormy argument, maybe) said that, although we had to sell it in a 500 mL bottle, I could make between 300 and 250 mL. I chose the highest limit because, at least, the bottle would have looked fuller.
If reading this you think: “It’s all incredibly boring: the prescription is boring, the pictures are boring (although you can see my hand. Wow!) and, above all, this guy sounds terribly boring”, well, it’ll mean I’ve been very good at portraying my most exciting working day this week.

After only two weeks, I realised I’ve always been right thinking I’d have done anything to not work at a chemist’s shop for the rest of my life. I chose Industrial Pharmacy, rather than Pharmacy, because that was something I had clear in my mind even at the high school, when, fortunately, I had limited experience of chemist’s shops as a costumer, too.
The only difference between now and then is that I don’t want to synthesize drugs any more, but I’m going to be a molecular biologist.

On my first week, I’d admit, everything was new and fresh: the colleagues, handling drugs I had only studied, some hard, manual work such as tiding up drawers and looking after the stockroom. And the galenic preparations seemed to increase number as people were coming back from holidays.

Now, instead, I’ve realised what an impossibly annoying job this is. I’m sorry but I haven’t worked hard for four years to work as a clerk, placing boxes on shelves. And, to tell you truth, this is not even the worst part of the day. It’s when you have absolutely nothing to do, that it gets unbearable.

If you think it’s better as a proper pharmacist, you’d be wrong: yes, you are paid and, rarely, your knowledge of pharmacology has to be brought out but, sadly, these are very uncommon episodes in a week.
The fact that this is a very boring job is also confirmed by the huge number of absolutely stupid hobbies my colleagues have.

On Monday, I also saw Michael Moore’s latest film, “Sicko”. If you saw it, you’d probably remember he visits an English chemist’s shop. There, the man behind the counter says pretty much what I’ve written so far: he didn’t spend all those years studying pharmacy to sell, like his American counterparts, soap powders or washing-up liquid. Thing is that chemist’s looked much more “trustworthy” than the one I work at and, moreover, it’s just a job that I’ve always disliked because I felt it wouldn’t suit me.

All this long tirade serves primarily to make an announcement: given that I am allowed to do it, I’ll finish my internship in the middle of October so that I’ll be able to start my thesis long before the scheduled time (December). This is another advantage of having done the exams of 5 years in 4.
Although I’m certainly on holiday at the moment (even if I’m theoretically and officially working), a man can’t remain inactive for too long, can he? At least I can’t.

As I highlighted when outlining the forthcoming massive series of posts, the title for my frequent updates on the thesis in progress was likely to change and, in fact, it has: it’ll be called, following the success of French Laboratoire Organique, Molekularbiologie. I chose German because I wanted to emphasize how quickly and efficiently I’m ready to carry on the project.

Now, for what concerns the blog, given the lack of interesting stuff I can get out of my internship, I’ll launch a series of post dedicated to something I reckon to be one of the most intriguing I’ve ever seen: glass.

Stay tuned.