Use

The hard capsule is a drug form (or galenic form) used when the drug (or any other substance to be used by oral way) it contains, has a strong odor or an unpleasant taste that you wishes to mask. It's also used when the drug has a texture not easy to put in the form of tablet.

Normally, the active product must be a dry powder, because the gelatin disaggregates when in contact with water; it's possible to putliquids in a hard capsule, but only is included in an absorbing substate (aerosil for example), or right before swallowing the capsule (it is the case for essential oils).

Nevertheless, the hard capsules can be filled with oily liquids, but in industrial environment only. It's possible to hide in a capsule a smaller product as a compressed tablet or another smaller capsule, for example for clinical trials (known as in " double blind").

Especially treated hard capsules "gastro-resistants" or with "enteric coating" allow to avoid the anactivation of a substance by the stomach acidity, or allow to obtain a delayed release, in the intestine.

The hard capsule is mostly a packaging form easy to realize, with a cheap material, from where its success in hospital, in pharmacies, and even at private individuals doing themselves their mixtures of plants. Thanks to the many combinations of colors that it allows, and with the possibility to print logo and reference n°, the hard capsule makes it possible to personalize a drug or a food complement, with a marketing aim for example. This personalization is also useful for the poisons centers to recognize a product when there is an intoxication

There is also many other more "exotic" uses of the hard capsules: For example, thez are used to store electronics components, or fossils of small size.

Structure

The hard capsule consists of two encased parts: the “head” and the “body”: The body is longer and a little less broad than the head. It is the body that is filled filled with powder, and thus it is the volume of this body which is the normal volume of filling.

Gélule Vide

When one inserts the two parts one in the other (after filling), a light relief allows to block the body in the head, with the result that the filled hard capsules are less long than the empty capsules.

Composition

The traditional hard capsule consists of gelatin of ox or pig (this gelatin is obtained by partial hydrolysis of the collagen contained in the bones or the skin); the gelatin can be added with opacifying products (titanium dioxide for example) and with dyes. It can also be simply left transparent

There is also vegetable hard capsules, containing modified cellulose (Hydroxypropylmethylcellullose, or “HPMC”, or “Hypromellose”) which had a certain success at the time of the “mad cow” epidemic (or “ESB”).

It should be noted that the traditional gelatin capsules from now on are guaranteed free from risks related to this disease. The vegetable capsules continue to be preferred for the “bio” products.

Finally, there is also capsules made with fish gelatin.

Size and weight

For the regular hard capsules, the various sizes go from “000” (largest) to 5 (smallest).

Taille standard des gélules vides

There is also much larger capsules, for veterinary use, as well as “lengthened” capsules, or even capsules especially reserved for the clinical trials

Sizes

000 00 0 1 2 3 4 5
Capsule length when closed 26,1 23,3 21,7 19,4 18 15,9 14,3 11,1
Body length (en mm) 22,2 20,2 18,4 16,6 15,3 13,6 12,2 9,3
Head length (en mm) 12,9 11,7 10,7 9,8 8,9 8,1 7,2 6,2
Body diameter (en mm) 9,5 8,2 7,3 6,6 6,1 5,6 5,0 4,7
Head diameter (en mm) 9,9 8,5 7,6 6,9 6,3 5,8 5,3 4,9

Source : « Technical Reference File 1st edition CAPSUGEL – Gélules Coni-Snap Poids

000 00 0 1 2 3 4 5
Weight (mg) 163 118 96 76 61 48 38 28

Filling methods

It's possible of course to fill the capsules by hand, but it's rather tiresome and the regularity of the filling, therefore the uniformity of the amounts, is very random.

Thus, it exists more or less sophisticated machines, as small plastic fillers for an occasional use, up to automated rotary fillers, used in the industry

The traditional capsule filling machine used in Pharmacy, for example for a capacity of 100 capsules simultaneously filled, consists of a “loader”, or “orienter”, which allows to put directly all the capsules with the head in top, and to place them in the holes of a second apparatus, the filler itself:

This one is composed of various perforated plates, which successively make it possible to block the bodies of the capsules, then to extract the heads, in order to leave the bodies apparent, in order to fill them with powder, then to seal the heads by blocking

In addition to its price, the characteristics to be considered at the time of the purchase of a filler are :

  • Its capacity in capsule number: There exist models for 50,60,100,120,200 and 300 capsules
  • Size of the hard capsules it allows to use, and the possible existence of sets of replacement plates to make other capsule sizes on the same filler
  • A loader option, that become essential as soon as the filler is often used; and even the existence of an electric orienter, for the semi-industrial machines
  • Material used: The plastic is frequent, but the stainless steel or the aluminium allow a hot cleaning, out of washing machine for example
  • The robustness, to privilege as soon as the production volume is high

All these characteristics will condition the number of capsules which it is possible to make per day, very theoretical capacity of course since it depends on the number of batches, or of prescriptions to be prepared, and thus times of cleaning necessary.

This capacity goes thus from 1.000 to more than 20.000 capsule per day, and even much more with industrial rotary fillers.

Filling volumes

In volume

000 00 0 1 2 3 4 5
Volume (ml) 1,37 0,91 0,68 0,5 0,37 0,3 0,21 0,13

Source : « Technical Reference File 1st edition CAPSUGEL – Gélules Coni-Snap

In weight (depending on the powder density)

000 00 0 1 2 3 4 5
For a density of 0,6 g/ml (mg) 822 546 408 300 222 180 126 78
For a density of 0,8 g/ml (mg) 1096 728 544 400 296 240 168 104
For a density of 1,0 g/ml (mg) 1370 910 680 500 370 300 210 130
For a density of 1,2 g/ml (mg) 1644 1092 816 600 444 360 252 156

Source : « Technical Reference File 1st edition CAPSUGEL – Gélules Coni-Snap

Market

The worldwide market is estimated (year 2000) between 1500 and 2000 billion capsules; the European market is approximately 400 to 500 billion.

The main manufacturer is Capsugel (Pfizer Group), with more than half of the market.

Legislation

In France, the hard capsules are regarded as “formulation elements”, and for this reason, belong to the “pharmaceutical raw materials”.

The “preparations good practices” recently introduced in pharmacy and hospital require from capsules suppliers a quality certificate delivered by the AFSSAPS (French Agency for the control of Health products) after audit, and the supply of a certificate of analysis with each batch of capsules.

History

The capsule, in the form of capsule or of seal, is used for a very long time: One thus found some among Egyptians! The seal, or “unleavened seal” is the ancestor of the modern hard capsule. It consists of two unleavened bread cups, which one moistened the edges to stick them

LGA, “Laboratory of the capsules and unleavened”, was since 1891 manufacturer of unleavened seals, but this form fell in disuse and the production is stopped for about fifteen years !