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СATALOGUE / PHARMACEUTICAL PRODUCTION TECHNOLOGIES / Filling technologies for hard gelatin capsules

Filling technologies for hard gelatin capsules

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  • Methods of filling solid gelatin capsules
  • Production of medical capsules
  • Gelatin capsules in a blister pack
  • Equipment for filling solid gelatin capsules
  • Horizontal flow pack packaging machine
  • Mixing of pharmaceutical powder
  • Vials plastic packaging

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СATALOGUE / PHARMACEUTICAL PRODUCTION TECHNOLOGIES / Filling technologies for hard gelatin capsules

Filling technologies for hard gelatin capsules

Over the past few years, capsule filling technology has undergone significant changes in the pharmaceutical industry. The principle idea of capsule filling has expanded from filling with solid dosage forms to filling with liquid dosage forms. Until recently, soft gelatin capsules were the only alternative for encapsulation of difficult to dissolve dosage forms. Today, new technologies have been developed to fill hard gelatin capsules with liquid drug substances and seal them as an alternative replacement for soft gelatin capsules. This simplifies the capsule filling process and avoids many of the problems associated with filling soft gelatin capsules. The fundamental differences between filling hard and soft gelatin capsules are as follows. Moisture content. Hard gelatin capsules can have a moisture content of up to 50%. Soft gelatin capsules consist of a plasticizer that retains up to 30% moisture. As a consequence, the moisture absorption capacity of soft gelatin capsules is much higher than that of hard gelatin capsules. Another property of plasticizer is the migration of excipient into the walls of soft gelatin capsule, which can lead to changes in the formulation of the drug substance. Oxygen transfer level. In soft gelatin capsule film, the oxygen transfer level increases with increasing levels of glycerol and moisture. Since hard gelatin capsules have minimal plasticizer content, their wall permeability is lower than that of soft gelatin capsules. As a result, hard gelatin capsules can be filled with medicinal substances with high odor permeability, such as fish oil, valerian, and garlic oil. In addition, the aesthetic appearance of the dosage form is a concern for many manufacturers. This problem is easier to solve when filling solid gelatin capsules with liquids and sealing them, as there is a whole range of colors to improve their appearance. Biological activity. The biological activity of difficult-to-dissolve drug substances can increase significantly if these substances are “packaged” in hard gelatin capsules, which makes their use possible and improves the effectiveness of the drug. Dissolution Temperature. Materials with low dissolution temperatures (or those materials that become liquid at room temperature) are difficult to produce in powder form.

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

Model: Filling of hard gelatin capsules

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In addition to gelatin capsules, polymeric capsules are used in the pharmaceutical industry. Let us explain their use by one example. Scientists at the Faculty of Chemistry of Lomonosov USA State University proposed to give insulin in tablets instead of injections to diabetics. They developed a multilayer polymer capsule that protects insulin from the destructive action of gastric juice. This invention has largely made life easier for diabetics, as they have to take regular injections (up to several times a day) to control their blood sugar levels. But the fact that insulin breaks down quickly in the acidic environment of the stomach makes it very difficult, if not impossible, to create insulin in tablets. Scientists have found a way to protect insulin from gastric juice while preserving its properties by creating a multi-layered polymer capsule. In an acidic environment it is stable and remains intact, while in a neutral environment it gradually releases insulin. To create such a capsule, the scientists used two polymers: positively charged protamine and negatively charged dextran sulfate. They were successively layered on top of each other on the principle of “plus to minus”, forming a multilayer shell around the insulin filling, which makes up to 85% of the entire microparticle. The insulin in the protective capsule is stable at pH between 1.7 and 5, and is released at higher pH values. This pH dependence of protective polymer capsules makes it possible to create insulin in tablets. In the stomach, where the environment is very acidic, the capsules will protect the insulin molecule and prevent it from breaking down. After passing through the stomach and reaching the small intestine and ileum, where the pH reaches 6-8 units, the capsules will begin to release insulin intensively. From the small intestine, insulin can enter the bloodstream. It turns out that the capsule itself will determine where to keep the insulin closed and where to release it. The substances used to create the capsules are natural biodegradable polymers. They are easily broken down by enzymes and excreted from the body without causing any harm to health. All the above-mentioned diversity in approaches to the creation of capsule compositions and technology of their production must be taken into account in the development of drugs in the form of capsules. Each drug substance, possessing inherently specific physicochemical, pharmacological and pharmacokinetic properties, requires an individual approach to the creation of a dosage form. This is taken into account by scientists in the development of encapsulated pharmaceuticals.

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Technical specifications

Currently, the capsule manufacturing process is continuously monitored by sampling at each stage of production. Parameters such as dimensions, visual defects, moisture content, color and microbiological purity are continuously monitored during production. If a defect is detected, the entire batch is withdrawn regardless of the stage of readiness. The capsules are subjected to all types of analysis once again at the end of the production process, after which the final result of the quality check is issued. In recent years, capsules with specified release properties of the active ingredient have become more and more widespread – these are intestine-soluble capsules (with release of the drug substance in the intestine) and so-called retard capsules (with prolonged release). Creation of enteric soluble dosage forms is carried out in order to prevent the release of the active substance in the stomach (to ensure the stability of the drug substance, to prevent its concentration decrease under the action of gastric juice, to reduce possible side effects, to prevent possible undesirable neutralization of gastric juice, etc.). Intestine-soluble capsules are produced by two methods: by applying film coatings to the finished and filled capsule. Special compositions are used to coat capsules, the main components of which are most often shellac, cellulose derivatives (e.g., simple or esters), polymethacrylates, copolymers (styrene and maleic acid, vinyl acetate, caproic acid, etc.), natural waxes, sodium alginate and others; intestine-soluble properties are imparted to the filler itself – intestine-soluble film coatings are applied directly to granules, pellets or microcapsules. Along with the previous method, this method is by far the most demanded in the production of enteric soluble preparations in capsule form. To give prolonged properties to capsulated drugs use technological methods of introducing special ingredients in the composition of the filler for capsules. Usually used combinations of substances that prevent the rapid release of the active components of the dosage form, among which the most used are indifferent to the human body acrylic polymers (Eudragit several brands), cellulose derivatives (microcrystalline cellulose, oxypropyl methyl cellulose, methyl cellulose, etc.), some other substances.

Additional information

Currently, the dosage form in the form of gelatin capsules has become very popular with pharmaceutical manufacturers, consumers and physicians due to a number of advantages and positive characteristics. These include, among others:
High dosing accuracy of the drug substances placed in them. Modern equipment ensures high accuracy of filling capsules with filler (with a tolerance not exceeding ±3%) and minimal losses. High bioavailability. Studies have shown that capsules often disintegrate faster in the human body than tablets or dragees, and their liquid or unabsorbed solid contents are more quickly and easily absorbed. The pharmacological action of the drug substance is manifested in 4-5 min. High stability. Drug substances in capsules are protected from various unfavorable environmental factors – the effects of light, air, moisture, mechanical influences – due to the shell, which provides a sufficiently high tightness and isolation of components. Therefore, in the manufacture of capsules it is possible to avoid the need to use antioxidants or stabilizers or reduce their amount.
Corrective ability – unpleasant taste and odor of medicinal substances is eliminated, which is especially important in pediatrics. High aesthetics – achieved through the use of various dyes in obtaining capsule shells. Today, leading pharmaceutical companies use up to 1,000 different colors and shades for coloring capsule shells.
Possibility to set specific properties of drug substances – creation of intestine-soluble capsules, as well as urethard capsules (with prolonged drug release), which can be achieved by various technological methods.

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