The production process of capsules of the type softgel - definition and key steps

Soft capsules (softgel) are one-piece shells with flexible, soft walls, usually filled with a liquid or semi-solid medicine or supplement. Their shell is thicker and more plastic than in hard capsules due to the content of plasticizers, which allows for hermetic sealing of the liquid content inside. The shell of such a capsule consists mainly of gelatin (derived from animal collagen) and a plasticizer (e.g. glycerol or sorbitol) and water, with added dyes, opacifiers (e.g. titanium dioxide) or preservatives - depending on the needs.

Nowadays, alternative polymers of plant origin (e.g. modified starch or cellulose derivatives such as HPMC) are increasingly used to produce capsules. softgelto meet vegetarian requirements.

Below is a complete, technically correct description of the capsule production process. softgel, covering all key stages – from preparation of the gelatin mass, through encapsulation, final processing, to quality standards and regulations.

Preparation of gelatin mass (capsule shell)

Encapsulation process (capsule filling and forming)

After preparing the gelatin mass and the parallel preparation of the filling material, the actual capsule formation and filling takes place. softgel, or the encapsulation process. In the history of pharmacy, several methods of producing soft capsules have been developed: the plate method, the rotary die method, the reciprocating die method and the special Accogel method for encapsulating dry materials.

Nowadays, the most commonly used method is the rotary-matrix method, invented in 1933 by RP Scherer, which allows capsules to be formed and filled in a continuous cycle. This method ensures high efficiency and repeatability, which is why it dominates in the industrial production of capsules. softgel (the remaining methods have historical or niche significance).

Preparation of the batch (filling)

In parallel with melting the gelatin, the filling mass is prepared – it can be an oil, solution, suspension, emulsion or semi-solid mass containing the active substance. The ingredients of the charge are mixed and, if necessary, homogenized (e.g. in the case of suspensions) and degassed under vacuum to remove air bubbles. It is important that the filling mass has the appropriate viscosity and uniformity – often, the charge is continuously stirred until the moment of encapsulation, especially if it is a suspension, to prevent sedimentation of particles. The finished charge is kept in a feeding tank (also heated or thermostated, if the viscosity of the liquid requires it) waiting for encapsulation. It is also important to limit the water content and the appropriate pH of the charge – too high humidity or inappropriate pH could dissolve or weaken the gelatin casing during or after encapsulation.

Capsule formation (rotational die method)

The encapsulation process takes place in a special automatic soft capsule machine, integrating the feeding of the gelatin mass and the feed and the formation of capsules in one continuous cycle. First, the liquid gelatin mass from the service tank is pumped to the so-called distribution box, from where it flows evenly onto two opposite, rotating, cooled stainless steel drums. On the surface of these drums, the gelatin mass is cooled with cold, dry air (typically around 14–15°C and at a humidity of around 20% RH), which causes it to solidify into a continuous, elastic gelatin ribbon of equal thickness. One such ribbon (tape) comes off each drum. Then the gelatin ribbons are guided towards each other and end up between two rotating rollers with pockets cut out in the shape of a half capsule. At the same time, the liquid charge is dispensed: the dosing pump delivers a measured portion of liquid through a wedge-shaped nozzle placed precisely between two gelatin ribbons, just before their point of connection. As the rotating dies approach the two ribbons, a dose of liquid is injected between the two gelatin layers, filling the pocket that forms the capsule shape. Both gelatin strands are welded together around the charge – the connection is achieved by the pressure exerted by the dies and the action of heat (the dosing wedge and the dies are slightly heated to ensure a tight connection of the halves). As a result, a closed, filled capsule is created from each pair of die pockets softgel. The continued rotation of the rollers causes the formed capsule to be cut off from the surrounding gelatin film (the so-called extrudate). The remaining unused gelatin network (the so-called scrap or "netting") is drawn off by a separate mechanism to a waste tank or recycling system (some of the gelatin can be reused after melting, if GMP procedures allow it.

Softgel closed using the rotational method, it is immediately sealed tightly – the capsule leaving the matrix has its content hermetically sealed, and the welded spot (seam) is thin and durable. For the process to proceed correctly, precise synchronization of three parameters is crucial: temperature (maintaining the right range so that the gelatin is plastic but no longer liquid – this affects the effectiveness of welding), dosing in time (the injection point of the liquid portion must be perfectly matched to the moment of forming the pocket) and the pressure/pressure of the rollers (this determines the shape of the capsule and its cutting off from the rest of the ribbon).

Encapsulation process control

The process is fully monitored and controlled in accordance with GMP requirements. Operators and automation systems continuously check parameters such as: thickness of the gelatin ribbon, speed of rotation of the dies (encapsulation rate), temperature of the dosing wedge, gelatin mass and charge, and ambient conditions (temperature and humidity in the room). The mass of the capsules being formed is also regularly checked - both the total mass of the capsule and separately the mass of the casing and the mass of the filling (this can be estimated by controlling the density of the charge and the thickness of the gelatin). In this way, the uniformity of the dosage in each capsule is ensured (in accordance with the requirement of uniformity of doses). Modern machines are equipped with PLC control systems with touch panels, which allows programming and maintaining optimal settings and alarming in the event of parameter deviations from the norm. Additionally, lubricants or neutral oils are sometimes used to prevent the gelatin from sticking to the dies. All these measures guarantee high quality of the formed capsules and minimize the number of rejects.

After forming and cutting, the soft capsules fall out of the machine (onto a conveyor belt or into a container). At this stage, they are still moist and soft – the shell contains a significant amount of water, giving it the plasticity needed for forming. Immediately after encapsulation, the capsules are not yet ready for packaging – they require a series of final operations: drying, maturing, quality control, cleaning/polishing, sorting and packaging.

Final processing (drying, polishing, sorting, packaging)

Quality control, sorting

Once the capsules are dry, their quality is checked and any defective pieces are removed. At this stage, the capsules should meet the requirements for shape, dimensions, weight, strength and tightness. Automatic inspection machines are often used – capsules are transported in a way that allows each one to be inspected (e.g. on a belt under cameras). Vision systems are used to check the surface and shape of the capsules from all sides; damaged capsules (e.g. with leaks, dents, deformations), stuck pairs, discoloured or outside the size specification are automatically rejected to a separate line. Sorting ensures that only capsules that meet the quality criteria for appearance and uniformity go to the next stages. Some sorting systems additionally check the weight of individual capsules (e.g. by electronically weighing each capsule on the belt) and can also reject those with weight deviations.

Cleaning and polishing

Soft capsules, after drying, may have traces of neutral oil on their surface (used as a lubricant during molding) or other impurities (e.g. dust, gelatin fragments). In order for the final product to be aesthetic and clean, the capsules are polished. This is most often done in drum or rotary polishers, lined with soft material (felt, fabric), possibly with the addition of polishing agents. The capsules are rotated, rubbed gently against the material, which removes any deposits from their surface and gives them shine. Alternatively, air jet polishing with soft brushes is used. After this operation, the capsules have a smooth, dry and shiny surface, do not stick to each other and are ready for packaging. At the customer's request or for product identification purposes, before packaging the capsule softgel can also be printed or embossed/laser marked – these techniques are adapted to the soft surface of the capsules and performed with special devices after the polishing stage.

Packing

The final stage is the packaging of ready, tested capsules. It takes place in conditions that guarantee the preservation of quality – the packaging rooms are also air-conditioned so that the capsules do not absorb moisture from the air. Depending on the intended use, soft capsules are packed: loosely (into collective packaging – this is how the product is delivered, e.g. for further packaging), into containers (plastic or glass bottles with an attached moisture absorber), or in blisters (individual immersion of capsules in pockets made of PVC/Al foil, often with high barrier properties). Automatic counters and dispensers are used to fill the bottles – the capsules are counted and dropped into the bottle, after which the bottle is closed and labelled on an integrated line. The entire packaging process is also subject to control – the uniformity of the packaging filling, the tightness of the blisters, the correctness of the labels and batch numbers are checked. The packed capsules are a finished product that is put on the market after obtaining the appropriate quality certificates.

Quality standards and regulations (USP, EP, FDA, GMP and others)

Capsule production softgel takes place in a strictly supervised quality and regulatory regime. Good Manufacturing Practices (GMP) are the foundation - all stages (from raw materials to packaging) must be performed in accordance with procedures ensuring product repeatability and safety. In practice, this means, among others: control of the production environment, calibration of equipment, validation of processes, training of personnel and full documentation of each stage. The capsule production rooms are kept clean in accordance with the cleanliness class (usually ISO 8 for non-sterile forms, which corresponds to the limits of particles in the air for pharmaceutical production). The personnel apply the required hygiene measures (protective clothing, hand washing procedures, etc.) to minimize the risk of contamination. Particular emphasis is placed on microbiological control - both of raw materials (e.g. gelatin should come from sources free of prions, with a BSE/TSE certificate), as well as the environment and semi-finished products (gelatin mass maintained at an elevated temperature, bioburden testing, etc.).

Raw materials and materials must meet the requirements of the relevant pharmacopoeial monographs: e.g. gelatin used for capsules should meet Ph. Eur./USP requirements (concerning, among others, purity, bloom gel strength, viscosity, ash content). Plasticizers, dyes or preservatives - if used - must also be approved for pharmaceutical use. Fillers (API and solvents/carriers) must comply with quality requirements (e.g. USP-NF grade for oils, glycerin, etc.). Each batch of raw materials undergoes an incoming inspection in the quality laboratory, and the recipes are designed so that the components do not enter into undesirable reactions with each other (e.g. incompatibilities between polyol plasticizers and ester drugs that could lead to hydrolysis are avoided).

Product quality control: According to the European Pharmacopoeia and USP, finished soft capsules must meet a number of quality tests. These include:

• Uniformity of dosage units – each capsule should contain an amount of active substance within a specified tolerance. This test can be performed by a content uniformity test (single capsule assay) or mass uniformity test, depending on the API concentration.
• Disintegration or dissolution – capsules must release their contents within a specified time. Often, instead of a disintegration test, a dissolution test is performed directly, measuring the rate of release of the active substance from the capsule under conditions simulating the gastrointestinal environment.
• Uniformity of appearance and dimensions – capsules should be evenly colored, free from stains, blisters, cracks; their shape and size should comply with the specification.
• Mechanical strength – tested, for example, indirectly through abrasion or compression cracking tests; capsules must not crack or leak under normal conditions of transport and handling.
• Water content in capsules – to ensure stability, capsules are checked to ensure they have the correct residual moisture content (too moist and they may mould or leak, too dry and they may crack).
• Microbiological purity – in line with the requirements for oral forms without preservatives (limits of CFU of bacteria and fungi, no pathogens such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella).

The production process is subject to validation – each phase (gelling, filling, drying) must be documented as being capable of consistently delivering a product that meets the established quality criteria (Validation: IQ/OQ/PQ – installation, operational and performance qualification of equipment and process). In-process control (IPC) involves sampling capsules during the process (e.g. for weight, seal tightness, shell moisture) to detect any deviations early. Each production run is assigned a unique batch number, and all raw materials and packaging used in its production are recorded in a batch report, allowing full traceability if needed.

Legal regulations: Capsules softgel, if they contain drugs, are subject to supervision by regulatory agencies such as the FDA (USA) or EMA (EU). The FDA requires compliance with cGMP (21 CFR Parts 210/211) and stability studies according to ICH guidelines to establish the expiration date of the product. In the case of dietary supplements in the US, separate, slightly more lenient cGMP requirements apply (21 CFR Part 111), but the manufacturer still has to ensure the quality and safety of the product. In Europe, manufacturers must have a GMP permit and are subject to regular inspections; the requirements of the European Pharmacopoeia for product quality and EU/GMP guidelines (EudraLex Volume 4) apply. Production of capsules softgel should also take into account ICH Q8–Q10 guidelines on pharmaceutical quality management, including Quality by Design principles and the use of PAT (Process Analytical Technology) to monitor critical process parameters in real time, where possible.

Modern technologies and innovations

In recent years, the capsule manufacturing process softgel is constantly improving. Examples of innovative solutions include: the use of new casing materials (vegan capsules based on polysaccharides instead of gelatin), improved mixing and degassing systems (mixers with vacuum control and automatic ingredient dosing), precise dosing systems with servo mechanisms ensuring a constant filling volume of each capsule, production line integration (machines combining several functions, e.g. continuous gelatin feeding, encapsulation and pre-drying in one line), as well as advanced vision control and sorting systems that significantly increase quality control efficiency. The introduction of robotics and automation reduces the share of manual work (e.g. automatic drying tray feeders, packaging robots), which reduces the risk of errors and contamination. Specialized capsule forms are also emerging softgel, e.g. twist-off capsules (with a torn-off tip, allowing the content to be squeezed out) or gelatin capsules for cosmetic applications (so-called cosmetic pearls) – their production is based on the same process, with the shape of the matrices being adjusted. All these improvements make the production process softgel becomes more efficient, repeatable and in line with the concept of continuous quality improvement, to the benefit of patient safety and the final quality of products.

Summary

Capsule Manufacturing Process softgel is a complex sequence of operations starting from the preparation of a homogeneous gelatin mass, through precise filling with a liquid charge and forming capsules using the rotary-matrix method, then controlled drying and final cleaning and control activities, up to the proper packaging of the product. Each stage is carried out under strict quality supervision in accordance with the requirements of GMP and pharmacopoeial standards, so that the finished product is characterized by homogeneity, durability and safety of use. Thanks to modern technologies, the soft capsule industry is still developing, offering increasingly efficient and more advanced production methods, meeting the rigorous requirements of the pharmaceutical and supplementation industry.