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СATALOGUE / PHARMACEUTICAL PRODUCTION TECHNOLOGIES / Production of hard gelatin capsules

Production of hard gelatin capsules

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СATALOGUE / PHARMACEUTICAL PRODUCTION TECHNOLOGIES / Production of hard gelatin capsules

Production of hard gelatin capsules

As mentioned above, encapsulated dosage forms are gaining importance due to their distinct advantages over other dosage forms. This section will consider the technology of production of hard gelatin capsules, which are the most widely used in the modern pharmaceutical industry, as well as the equipment used for their manufacture. Characterization of the main and auxiliary substances included in the composition of hard gelatin capsules. To obtain capsule shells, film-forming high-molecular substances capable of forming elastic films characterized by a certain mechanical strength are used. Such materials include casein, zein, simple and complex cellulose esters, fats and wax-like substances, as well as some synthetic polymers (e.g. copolymer of me-tacrylamide and methacrylic acid, etc.). However, these substances have not found widespread practical application for pharmaceutical capsules, and therefore, to date, the pharmaceutical industry produces predominantly gelatin capsules.
One of the most common molding materials for the production of gelatin capsules is gelatin – a high-molecular compound of protein nature.
It is a product of partial hydrolysis of collagen, which forms the main part of vertebrate connective tissue (bones, cartilage, horns, hooves, skin, tendons of cattle and pig skin). The protein molecule of gelatin is based on a polypeptide chain formed by 19 amino acids, most of which are essential for the human body. The main ones are: glycine (up to 30%), proline, oxyproline, glutamic acid, arginine and lysine.
Collagen from bones and animal skins is subjected to maceration (softening and loosening due to prolonged exposure to liquid) and purification by acids or alkalis, which break it down hydrolytically into virtually unbranched amino acid chains of various lengths, i.e. gelatin. Depending on the chain length, gelatin has a molecular weight of 40,000 to 100,000,000,The method of decomposition used determines the nature of the final product.

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  • Information updated : 28 / 04 / 2024
  • In stock
  • Manufacturer : 1 year for Production of hard gelatin capsules

Model: Hard gelatin capsules

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Most often titanium dioxide is used as a clouding agent, less often aluminum hydroxide or calcium carbonate. In addition, the composition of gelatin capsule shells may include: water-absorbing agents – substances” allowing to prevent moisture retraction from the capsule shell by hygroscopic substances, which can be used when filling capsules. For this purpose, it is recommended to use polypeptides, oligosaccharides, starch and its derivatives, as well as some other substances; disintegrants – substances that contribute to maintaining a constant level of capsule disintegrability during long-term storage (since gelatin, being a product of collagen processing, has the property of “aging”), as well as achieving a rapid release of the contents of the dosage form. Amino acids, proteins, casein, croscarmellose, tweens, sodium hydrogen carbonate can be used in this capacity. To achieve rapid disintegration of capsule shells, the technology of dispersing some gases (oxygen, nitrogen, carbon monoxide, argon, etc.) into the gelatin mass can also be applied, which, among other things, allows saving the shell material. Also noteworthy is the original method of treatment of gelatin itself with amber anhydride proposed by Japanese scientists; sliding agents – substances that prevent possible sticking of capsules. Usually D-mannite, D-sorbitol, xylitol are used (relevant primarily for soft capsules sold in countries with hot climates, and when it is impossible to comply with the rules of storage of this dosage form).
Other additives may be added to the composition of gelatin capsule shells. As already noted, hard capsules are designed for dosing loose powdery, granular and microgranular substances. They have the shape of a cylinder with hemispherical ends and consist of two parts: the body (body) and the cap; which should freely enter one into the other. General information on capsules was given in section 3.4. In this section, the technology of production of hard gelatin capsules and the equipment used to produce them will be discussed. The steps in the production of hard gelatin capsules are as follows: preparation of the gelatin mass; manufacture of hard gelatin capsule shells; and filling of hard gelatin capsules.

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Technical specifications

There are two types of gelatin: acid gelatin A and alkaline gelatin B, which differ in some physical and chemical properties. Usually in the manufacture of pharmaceutical capsules use mixtures of gelatin A and B, as it allows to obtain masses for the manufacture of capsule shells with the most optimal rheological characteristics (in particular, in terms of strength, viscosity, pH, iron content, etc.). Gelatin is easily and quickly digested by the human body even with severe gastrointestinal disorders, non-toxic and has no adverse reactions. A characteristic property of gelatin (from Latin gelare – to solidify) is the ability of its solutions to gel when cooled, forming a solid gel. Production of gelatin capsules is based on this property of gelatin. To obtain a stable capsule shell, the composition of the gelatin base may include various auxiliary substances approved for use: plasticizers, film formers, stabilizers, preservatives, correcting agents, dyes and pigments. In order to improve structural and mechanical properties and to ensure appropriate elasticity, increase strength and reduce brittleness of shells, plasticizers are introduced into the composition of gelatin mass. The most popular plasticizers are glycerin, sorbitol, PEO-400, polyethylene glycol, polypropylene, polyethylene sorbitol (3-15%) with oxyethylene (4-40%), hexanthropol and others. For the manufacture of hard capsules gelatin mass should contain a small amount of plasticizers (0.3-1.0 %), for soft – their amount increases to 20-45 %.
In some cases, gelatin capsules become more stable with partial or complete replacement of glycerol in the shell with sorbitol, PEO-400 or other plasticizers.
Among the disadvantages of gelatin capsules can be noted their high sensitivity to moisture, which requires compliance with certain conditions of storage of capsules. Therefore, sometimes gelatin capsules are coated with special coatings – film formers, which reliably protect the shells from moisture, while not preventing their rapid destruction in the stomach.

Additional information

Such film formers include para-aminobenzoate sugars and cellulose amino derivatives, which improve the moisture resistance of gelatin capsules. Another way to overcome the moisture sensitivity of gelatin capsules is to use zein or other moisture-resistant film-forming agents instead of gelatin. For encapsulation of complex compositions of vitamins Japanese researchers proposed a method of obtaining “double” capsules: water-soluble vitamins are covered with a film of wax-like substances, and then a hydrophilic film of gelatin. The gelatin mass is a favorable environment for the reproduction of microorganisms. To ensure antimicrobial resistance of shells in the composition of the mass introduced preservatives: a mixture of salicylic acid (up to 0.12%) with potassium (sodium) metabisulfite (up to 0.2%), benzoic acid and sodium benzoate (0.05-0.1%), nipagin (0.1-0.5%)” To give capsules an attractive commercial appearance or protect the active substances from photochemical reactions, the composition of the gelatin mass introduced corrective auxiliary substances. Sometimes aromatizing substances (essential oils, essences, ethyl-vanillin 0.1%) are added to the gelatin base to give capsules a pleasant smell. The addition of sweet substances (sugar syrup, sucrose, glucose, etc.) improves the taste of capsules and reduces the unpleasant sensation when swallowing. Currently, all capsules (with rare exceptions) are colored to give them a more aesthetic appearance. For this purpose, coloring agents are introduced into the gelatin mass. Different coloring is also convenient for the release of different names of drugs in the form of capsules, as it allows you to distinguish products by color. As dyes can be used substances of natural origin (carminic acid, chlorophyll, beta-carotene, etc.), the low toxicity of which allows their use without restrictions in most countries, inorganic pigments (yellow, red and black iron oxide, titanium dioxide), as well as organic dyes approved for medical use. The amount of dyes in one capsule, as a rule, does not exceed 50 mcg. Capsules intended to be filled with photosensitive substances should be opaque. For this purpose, obscuring agents are used – substances that make it possible to obtain opaque capsules due to their ability to form a stable fine suspension in the gelatin mass.

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