Capsule Making Definitions
Listed below are some terms and their definitions that are commonly used in the manufacture of capsules for the pharmaceutical and nutraceutical industries.
Active Pharmaceutical Ingredient (API)
An active pharmaceutical ingredient is defined by the USA Federal Drug Agency as ‘any substance or mixture of substances intended to be used in the manufacture of a drug product and that, when used in the production of a drug, becomes an active ingredient in the drug product’.
The term API often refers also to the pharmaceutically active component in medicine capsules. This could a pharmaceutical drug, vitamin, mineral, herbal extract or other supplement.
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The release of the contents of a capsule can be controlled according to the nature of the drug formulation and capsule material. The hydrophobicity of the formulation, including the capsule excipients will control the rate of release of the drug. The shell of the capsule can also be modified by making the coating semi-permeable. See also enteric-coating.
Auger filling machine /method
When manufacturing capsules using a capsule filling machine, powder is pushed into each capsule using a rotating auger (screw) that sits inside a hopper. This ensures flow of the materials and encourages the powder to move through the machine. Powder is fed continuously out of the hopper due to rotation of the auger. The amount of powder fed into the capsule depends on the capsule size, the time the capsule body spends under the hopper, and the speed of rotation of the auger (slower rotation increases fill weight).
The body of a capsule is the section that the powder sits in before the cap is pushed on to seal it.
Cap or Caps
The cap can also refer to the top part of the capsule that sits on top of the body. Empty capsules are sometimes referred to as caps, hard caps or gel caps.
In the pharmaceutical industry a capsule usually refers to a relatively stable shell that encloses a dose of active ingredients allowing them, for example, to be taken orally or to be used as suppositories.
The two main types of capsules are:
- Hard capsules, which are typically made using gelatin but are also made using HPMC and Pullulan. Empty capsules are then filled using with dry, powdered ingredients or miniature pellets e.g., made by extrusion. Hard capsules are made in two halves: a lower-diameter ‘body’ that is filled with the powder ingredients and which is then sealed using a higher-diameter ‘cap’.
- Soft- capsules, primarily used for enclosing oils or active ingredients that are dissolved or suspended in oil. Soft capsules are made and filled in a continuous process.
Hard capsules are filled using a capsule filling machine. These are available in three main forms:
- Manual (Hand held) Capsule Filler
- Semi Automatic Capsule Filling Machine
- Fully Automatic Capsule Filling Machine
In each case, the powder or formulation that contains active ingredients combined with excipients are loaded into the powder hopper of the filling machine. Capsules are filled by admitting powder from the hopper into the body of the capsule, with the aid of filling rings.
Capsules are usually coloured by the addition of colourants to the gelatin solution during the manufacturing stage. Two types of colourant are commonly used: water–soluble dyes or insoluble pigments. The most common dyes are erythrosine, indigo carmine and quinolone yellow. The two types of pigments commonly used are iron oxides (black, red or yellow) and titanium dioxide (white and used to make the capsule opaque). To make a range of colours, dyes and pigments are mixed together as solutions or suspensions.
A type of capsule dosing machine that uses the capsule body directly to measure the powder fill. Uniformity of fill weight can only be achieved if the capsule is filled completely, e.g. using an Auguer filling machine.
A diluents is an excipient usually present in the greatest concentration in a formulation. Diluents make up the necessary bulk when the quantity of active ingredient is not sufficient to make up the required bulk. Example diluents include lactose, maize starch and calcium sulfate.
Disintegrants are substances added to tablet and some capsule formulations to promote the breakup of the tablet capsule contents into smaller fragments in an aqueous environment thereby increasing the available surface area and promoting a more rapid release of the drug substance. Example disintegrants are corn starch and microcrystalline cellulose (Avicel).
A type of hard capsule filling machine where the powder added is measured independently of the body in a special measuring device. Weight uniformity does not depend on filling the body completely. The dosator uses a piston tamp method in which the dosator head is inserted into a bed of powder, compacting the powder into the dosator body. The dosator is withdrawn from the powder bed, extracting with it a slug of compact powder. The dosator then moves above the capsule body where the slug of powder is ejected. There are many different types of dosator machine.
Dry granulation is a process used to form granules without using a liquid (aqueous) solution because the product granulated may be sensitive to moisture and heat. Forming granules without moisture requires the compaction and densification of powders. In this process the primary powder particles are aggregated under high pressure. A Sweying granulator or a high-shear mixer-granulator can be used for the dry granulation process.
A drying oven is designed to remove moisture. Typical applications are in the pre-treating of powder formulations, curing of painted tablets, and the preparation of gelatin capsules. Such ovens are also sometimes known as kilns, though they do not reach the high temperatures employed in kilns for firing ceramic materials. Hard gelatin capsules are formed from a gel at room temperature that is dried at different temperatures in a series of steps. Soft gelatin capsules contain 30-40% by weight of water in the wet formulation. The water content is reduced to around 10% by weight by passing the capsules through a series of drying ovens.
Enteric coated capsules resist disintegration in the stomach (low pH) but break down in the intestinal tract (high pH). Types of coatings applied include cellulose acetate phthalate and mixtures of waxes and fatty acids and/or their esters.
A mixture of peptides and protein. Gelatin is a translucent and brittle material that is made by the partial hydrolysis of collagen extracted from various animal parts. Pharmaceutical and photographic grades of gelatin generally are sourced from cattle bones and pig skin. A form of gelatin that may be acceptable to vegetarians can be obtained by extracting collagen from fish bones. Gelatin capsules are the most commonly used in manufacturing.
Gelcap / Gel-Cap
Informal name for gelatin capsule.
Granulation is the process making granules. It is specifically bringing together or aggregating powder particle by creating bonds between them. Bonds are formed by compression or by using a binding agent. If the particles of a powder are too small, they are very difficult to compress into tablet form. They would have to be compressed very slowly for a long period of time to make a worthwhile tablet. Unless the powdered is granulated, it could not efficiently be made into a tablet that has good tablet characteristics such as uniform content or consistent hardness. The granulation process combines powder particles to form larger granules that will allow the tableting process to be predictable and will produce quality tablets within the required tablet-press speed range. Granulated powder with uniform particle size and good flow properties makes it ideal for filling capsules.
– Also see: Wet Granulation, Dry Granulation and Granules.
A granule, in pharmaceutical usage, refers to a cluster of particles of medicinal powder or formulation that forms the basis for tablets. By themselves medicinal granules often have an unpleasant and bitter taste, making patients feel nauseous if taken in the powdered form. When the granules are compressed into a tablet or filled into a capsule these can be swallowed with the patient experiencing no effect of taste. This is beneficial as large quantities of the powder are often required even for a single dosage.
Preservatives and surfactants (wetting agents) may be added to the gelatin solution during capsule manufacture to aid in processing.
A material embedded in gelatin to make the softgel cell elastic and pliable. The most common plasticizers are glycerol, sorbitol and propylene glycol used either separately or in combination. The choice and concentration of plasticizer is important in ensuring optimal compatibility between the capsule shell and the liquid fill formulation. Typically plasticizers account for 20-30% by weight of the gelatin.
Rotary capsule machine
This machine has two cylinders located side by side, in each of which half-moulds are cut. The cylinders rotate in contrary directions. Two ribbons of gelatin are fed between the rollers, and just before the opposing rollers meet, jets of formulation press the gelatine ribbon into the moulds, filling each half. Immediately pressure is applied to the two halves, sealing them together to form a capsule. Rotary machines are capable of producing between 25000 and 30000 capsulese per hour with a dosage accuracy of ca. + 1 %.
A softgel is an oral dosage form of medicine similar to a hard capsule. It consist of a gelatin-based shell surrounding a liquid fill. Softgel shells are usually formed by a combination of gelatin, water, opacifier and a plasticiser such as glycerin or sorbitol.
Seamless gelatin capsule (Globex method)
Seamless capsules are manufactured using the principle of drop formation. The machine for making the capsules consists of two concentric tubes. The active formulation flows through the inner tube, and the gelatine solution flows through the outer tube. The material falls from the tubes into a bath of liquid paraffin or other inert liquid in which the gelatin is insoluble. Spherical drops are formed in which the formulation is encased in gelatin. Regular pulsed flow causes drops of the correct size to be formed. The bath of inert liquid is maintained at around 4°C or below which is low enough to ensure that the gelatine is rapidly congealed. Capsules are subsequently degreased and dried.
Sustained release capsule
The traditional method of taking a dose of medication three or four times a day leads to periods of excess and deficiency in blood concentration of the medicament. An alternative means of addressing this variation in efficiency, and reducing the number of doses per day, is to administer a capsule that contains a number of different coated pellets that release the drug successively over a long period. The pellets contain protective coatings of different thicknesses, designed to delay the release of API. Each coating can be coloured differently to facilitate identification and control of mixing.
Traditional wet granulation is the process of mixing and adding solution to the powder formulation and then transferring the product to a tray dryer. Mixing of the granulation liquid to the powder can be achieved by using a high-shear mixer or granulator, a twin-screw granulator, or a fluidized bed granulator. The mixing, or agitation, along with the wetting of the components within the formulation results in the aggregation of the primary powder particles to produce wet granules. The granulation liquid (fluid) contains a solvent which must be volatile so that it can be removed by drying, and be non-toxic. Typical liquids include water, ethanol and isopropanol either alone or in combination. The liquid solution can be either aqueous based or solvent-based. Aqueous solutions have the advantage of being safer to deal with than solvents.