Hard Gelatin Capsules
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Introduction
The capsule shell The shell of hard gelatin capsules basically consists of gelatin, plasticizers and water. Modern day shells may, in addition, consist of preservatives, colours, opacifying agents, flavours, sugars, acids, enteric materials etc. The gelatin is marketed in a large number of varieties and a specific quality and gelatin having specified gel strength, viscosity, iron content etc. should be selected for capsules. The variations in gelatin properties arise because of changes in molecular weights and methods followed in conversion into gelatin. The average molecular weight of gelatin, varies between 20,000 and 2,00,000. Two popular grades of gelatin, Pharmagel-A and Pharmagen-B, are acid processed and alkali processed respectively. They have differing isoelectric points (Pharmagel-A: pH. 4.8 to 5.2, Pharmagel-B: ph 6.5 to 9.5). For capsule shells generally a mixture derived from pork skin and bones is used. Pork skin gelatin contributes plasticity while bone gelatin gives firmness. However, in using bone gelatin its calcium phosphate content should be watched since undue amounts can make capsules hazy. One important reason for the exclusive use of gelatin for making hard and soft capsules is its solubility characteristics in stomach fluids. It absorbs cold water readily, though the rate of absorption depends upon moisture content of gelatin.
The plasticizers used are glycerin, sorbitol etc. The exact proportions of gelatin and plasticizers have to be determined on the
basis of the use of capsules and their storage conditions. Preservatives, if included, are generally a mixture of methylparaben
(4 part) and propylparaben (1 part ) to the extent of 0.2%. Flavours, if added, should not exceed 2% and are generally
ethylvanillin or essential oils. Sugar, if included, may be up to 5% ot give the gelatin shell desirable chewable
characteristics.
The capsule shells are nowadays produced on mass scale by sophisticated machinery. Fundamentally speaking, in every machinery,
pairs of pins corresponding to the bodies and the caps of the capsules are dipped in heated gelatin solutions containing the
necessary additives. The dipping is followed by withdrawal of pins and their rotation a few times to distribute the solutions
evenly. Cold air is simultaneously blown on the rotating pins to firm up the gelatin shells. These pins are, thereafter, passed
though series of kilns with controlled rates of drying. After drying, the bodies and caps are remove4d from pins by mechanical
jaws and are trimmed to appropriate lengths by rotating blades. Finally the caps are placed on the bodies.
The capsules shells should be stored under controlled conditions of temperature and humidity. The normal moisture content of
shell is 10 to 15%. Under conditions of low humidity they may soften and grow tacky. The shells for human use are marketed in 8
size depends upon its density and compressibility. Normally the shell manufacturers give a guidance of the approximate quantities
of selected drugs that can be contained in different sizes. For instance, data from Parke Davis & Co. with respect to aspirin
is reproduced below:
For veterinary use larger capsules Nos. 10, 11 and 12 approximating to capaciti9es of 30, 15 and 7.5 gms. are also marketed.
Materials to be filled
The materials to be filled in the hard capsules may need formulation to a certain extent and the following additives may have to be incorporated:
Diluents
The dose of a particular medicament may be enough to fill in a suitable size of the capsule. But there may also be occasions when it is too small in bulk falling far short of the quantity needed for smallest available capsule size.
In such instances one or the other diluents has to be added to bring the medicament up to a desired bulk. The usual diluents selected are lactose, mannitol, sorbitol, starch etc. The quantities of diluents are related to the dose of the medicament and the capsule size.
Protective sorbents
In some cases inclusion of inert materials may be called for to physically separate incompatible or eutectic substances. Sometimes some inert materials are included to prevent absorption of moisture by hygroscopic substances. Materials like oxides and carbonates of magnesium or calcium are suitable for these purposes.
Glidants
Glidants become essential when the powders are filled by s\automated machinery requiring their regular flow into the capsule bodies many materials by themselves lack the desired degree of flow and hence glidants like talcum, stearates etc. are included in suitable amounts.
Anti-dusting compounds
In large scale filling operations dust is a real problem and if allowed to go unchecked, can pose serious health hazards for the workers. Presence of potent drugs in the dust can cause its continuous inhalation. Hence, material to be filled in the capsules should include some anti-dusting components like inert edible oils. The quantities of oils have to be carefully worked out since excessive amounts can cause the particles to cohese together.
Although normally only powders are filled but on occasions fixed oils and other liquids, that do not permeate through gelatin wall, can be filled in the hard capsules. Filling of liquids is done by the use of calibrated droppers or pipettes. The other materials to be filled in could be plastic dough like masses rolled into uniform pipes. Before filling pipes are cut into uniform pieces and put in the capsules. Sometimes potent drugs are filled in the form of small tablets or pellets and are then covered with inert materials to fill the body. Granular materials can also be conveniently filled in the capsules.
Substances which are highly soluble in water lice citric acid, sodium chloride and ammonium compounds should not be filled in gelatin capsules since they may affect the gelatin shell owing to abstraction of water from it. Some water soluble substances may also migrate into the gelatin shell thus reducing potency of the encapsulated substance. Excellent examples were thiamine HCl and ascorbic acid. Sometimes even poorly water soluble substances like benzocaine migrate into the shell.
Filling
Extemporaneous filling of a small number of capsules is possible by spreading the powder to be filled in on a tile or a sheet of paper and pressing the body of capsule on to it until it is full. Cap is inserted on the body and the capsule weighed against a tare of empty capsule to get a feel about the drug amount. It may be necessary to fill in some more or tapout some filled in material in case of variations in weights beyond permitted limits. On an industrial scale semi automatic or fully automatic equipment is used for filling. In these operations the caps are removed, bodies filled, caps replaced and filled capsules ejected. Some machines can fill 15000 to 20000 capsules per hour.
Finishing
The filled and sealed capsules necessitate a finishing operation before inspection, bottling or packing in strips/blisters and labeling. The following steps are involved in the finishing process:
Salt Polishing
In salt polishing, the capsules are rotated in a coating pan type device along with sodium chloride granules. Later the capsules and granules are separated by screening on a suitable device. Such a polishing removes adhering materials from the surfaces of capsules. However, salt polishing should be done before imprinting, if any, since imprinting may be affected by salt.
Cloth dusting
In this process individual capsules are rubbed with cloth which may or may not contain inert oil. This removes some remaining materials and also imparts improved gloss.
Brushing
In brushing capsules are projected under soft a rotating brush which removes all remaining âDustâ. This operation must be
supplemented by exposure of capsules to regulated vacuum.
Inspection
This process is desirable to pick up imperfect and damaged capsules manually or with automated inspecting systems.
Sealing and locking
Sealing and locking devices invented by various manufacturers as their novelties are basically guards against separation of the caps from the bodies during handling, transport etc. However, incidently these devices do not permit any tampering of their contents ruling out foul play.
Sealing of the caps on to bodies is possible by moistening the upper part of the body and slipping the cap on. However, many manufacturers seal capsules by means of a coloured band of gelatin placed at the junction of the body and the cap. More recently some configurations have been developed in the bodies and caps which enable their mechanical locking. For instance, Snap Fit capsules, marketed by Parke Davis, have matching interlocking rings on the body and in the cap. Another method suggested is to bring a hot needle like structure against the cap where it overlies the body to form a sort of spot weld.
Some Modern Uses of Hard Gelatin Capsules
Traditionally hard gelatin capsules have been used for enclosure of powders or other solid substances like granules and pellets. Recently pastes and oils have also been filled in hard gelatin capsules. To prevent leakage of oily materials either thixotropic substances can be added or the cap and body joints banded with molten gelatin or sealed with lacquers.
Incompatible drugs also can be usefully supplied in capsules. Multilayer tablets are devices towards this end. But it would be more useful to make small tablets from each individual drug and encapsulate them all in one capsule.
Hard gelatin capsules have also been used for drug delivery in bronchial tract. The âspinhalerâ of Fisons has the drug in the micronized from in a capsule. To release the drug the capsule is punctured thereby releasing a fine powder mist which is inhaled into the lungs alongwith the breath. Maybe with passage of time some new applications are developed.
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