The Formal Introduction of Gelatin Capsules in America
From the proceedings of the American Pharmaceutical Association annual meeting, August 1896
Held in Montreal, Canada
The Formal Introduction of Gelatin Capsules in America
Capsules received a formal introduction to the American Pharmaceutical Association (APhA) in August, 1896 in a presentation given by APhA member WM. C. Alpers. While capsules had been used by pharmacists and physicians for over fifty years, they were not yet listed in the US Pharmacopeia. For the annual meeting, Alpers prepared a historical background of the development of capsules and presented it as a means of formalizing the recognition of capsules as a dosage form.
Alpers’ related the history of Mr. A. Mothes of Paris, France, the inventor of the first patented gelatin capsules in 1834. The first capsules were used to successfully mask the taste and odor of balsam of copaiba without the use of excipients.
The method of manufacturing used a small leather pouch that was filled with mercury; these together created a mold. The mercury-filled pouch resembled the shape and size of a small olive. The mold was dipped into a solution made of one part gelatin and three parts water. A rotary motion helped to distribute the gelatin over the pouch, with additional dipping done as needed to form a consistent outer layer. Once the gelatin capsule layer was firm, the mercury was emptied from the leather and the collapsed skin was removed from the outer shell. The small neck opening of the capsule was trimmed, and it was then filled with copaiba oil (the medicine) by syringe. A small drop of gelatin was applied to the remaining hole, and the capsule was sealed.
While the new dosage form gained popularity for its successes, Mothes, and his partner DuBlanc were protective of their new product and for a time would not supply empty capsule shells for filling by other pharmacists. Similarly, competing pharmacists were protective of their custom formulations, and did not want to supply these to Mothes and DuBlanc for filling. This gave way to the exploration of alternative methods of using gelatin to hide the taste and smell of medications.
Alpers shared the case of a Parisian pharmacist, Mr. Garot, who in 1838 engineered a related but different method. Garot would use the active ingredients to form a mass, like a dough, and cut these into small pills. A needle was used to stab and pick up the pill, where it could then be immersed in the gelatin solution and then dried. Once dried, the needle was carefully warmed over a candle until the instrument could be removed. A spatula with a small amount of gelatin sealed the hole made by the needle. Great care was exercised to not allow the active ingredients to contact the outside of the gelatin shell so that taste-masking was as effective as possible. (original source: Journal de Pharmacie, 1838 p. 78)
Further methods were described in various places using molds such as wood (Bucharest), sheep intestine (London), and iron (France, Germany and the United States).
Particular to the United States, Alpers quotes the American Journal of Pharmacy in 1835 wherein Alfred Guillou (Philadelphia College of Pharmacy) described the following method:
“Provide a suitable number of narrow tin dishes, about 18 or 20 in length, ½ in. deep, and about 2 in. in width. In the length of these and in a line, plant or solder at a distance of one inch from each other a number of smoothly formed metallic knobs of an ovoid shape, whose apex having been somewhat lengthened out, forms a thin neck by which they are attached to the tin dishes. This neck may be about ½ of an inch in length. Procure a sheet of tin and perforate with round holes, of which the diameter will be equal to the thickness of the knobs. Having greased the knobs well with lard, so as not only to prevent any adhesion to them, but also the adhesion of the inner sides of the capsules to each other after casting, pour melted glue (the most transparent having been selected) upon them and allow it to become tolerably stiff. If you think the shell is too thin, a second coat may be poured upon the first. The capsule having been coated, this cast is allowed to cool down to the ordinary consistency of India rubber, and having run a knife around the neck, you twist it briskly around and pull it upwards off the knob. It will immediately collapse and lose the form imparted to it on the mould, but if laid aside to dry, will by the time it has hardened have regained the desired rotundity. Place it upon your perforated plate or “filler”, and you can thus conveniently fill it with the article prescribed, and close the opening with a piece of gold-beaters skin.”
Eventually empty two-piece capsules were manufactured and sold. This was a difficult process, as small variations in capsule wall thickness made the capsule joining process inconsistent. Automation would lead to greater consistency and lead to success for two-piece capsule manufacturing.
F.A. Hubel of Detroit, Michigan is credited by Alpers as securing the first patent for an automated machine to make empty two-piece capsules. Like manual manufacturing, the process involved dipping mold pins into a gelatin solution, and drying the gelatin, and cutting and stripping the two-part shells off the molds. In Hubel’s early machines, the capsule parts were then inspected and joined manually.
Albers quoted from a letter of “The Merz Capsule Company” of Detroit describing the difficulties:
“In order to make capsules properly and sufficiently cheap it requires a large amount of complicated and expensive machinery, and constant attention to small details, in as much as the one-thousandth of an inch difference, more or less, in the thickness of a capsule will either make it a loose-joining or a tight-joining capsule.”
As empty two-piece capsules became more available through mass production, their popularity and use soared. Another inventor, Mr. Heineman summed up several benefits as follows:
“By means of these (capsules) the druggist is enabled himself to fill elastic capsules as occasion may require, perfectly and without loss of time, doing the work as well as the capsule manufacturer himself could do the same in the factory. The convenient shells will keep almost indefinitely, are always ready for use, and enable the druggist not alone to avoid carrying a large stock of filled capsules, but enable him to dispense freshly made capsules containing an almost indefinite variety of formulas with whatever variations physicians may be pleased to give them from time to time, as the needs of the patient may require.”
