A capsule is a dosage form consisting of a hard or soft gelatin shell containing an encapsulation - one or more active ingredients with or without excipients.
Classification of capsules.
Depending on the content of plasticizers and on the technological principle, two types of capsules are distinguished:
- Hard capsules;
- Soft, full capsules.
Soft capsules get their name because during their manufacture, the filler is placed in a still soft elastic shell. The capsules are then subjected to further manufacturing processes, in which the original elasticity of the shell may be partially or completely lost. Such capsules have a whole shell, which can be elastic or rigid. Sometimes the shell of soft capsules contains the active ingredient.
Hard capsules are filled after the entire molding process has been completed, and they have achieved proper elasticity and rigidity. Solid capsules have a two-component structure and can be made in advance, and their filling with biologically active substances is performed as needed.
Currently, the dosage form in the form of gelatin capsules has become very popular among pharmaceutical manufacturers, consumers and doctors due to a number of advantages and positive characteristics. These include, but are not limited to:
- High dosing accuracy of the pharmaceutical substances placed in them. Modern equipment ensures high precision of filling capsules with the 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 dragées, and that their liquid or uncoated solid contents are absorbed faster and easier. Pharmacological action of the drug substance is manifested in 4-5 minutes.
- High stability. Drug substances in capsules are protected from various adverse environmental factors - light, air, moisture, mechanical influences - due to the shell, which provides a sufficiently high tightness and insulation of the components. Therefore, in the manufacture of capsules can avoid the need to use antioxidants or stabilizers or reduce their amount.
- Correcting ability - unpleasant taste and smell of medicinal substances is eliminated.
- High aesthetics - achieved through the use of various dyes in obtaining the capsule shells. Today, leading pharmaceutical companies use up to 1,000 different colors and shades to color the capsule shells.
- The ability to set certain properties for the drugs - creating enteric soluble capsules as well as retard capsules (with prolonged drug release), which can be achieved by various technological methods.
- Fewer excipients are used in the capsule production than, for example, in the production of tablets.
In addition, the capsules require less machinery due to fewer production steps and fewer techniques used than in the production of tablets.
In soft and hard capsules, drugs can be encapsulated in their unmodified form without the wet granulation, heat, and pressure as in tablet production. In addition, the number of factors affecting the release and absorption of drugs from capsules is much lower than for other dosage forms.
The disadvantage of gelatin capsules is their high sensitivity to moisture, which requires compliance with certain conditions of their storage. Another disadvantage is the fact that gelatin is an excellent breeding ground for microorganisms. This drawback is prevented by adding preservatives to the mass: nipagin (0.4%), nipazole (0.4%), sorbic acid (0.1-0.2%), etc.
Classification of capsules.
Depending on the content of plasticizers and on the technological principle, two types of capsules are distinguished:
- Hard capsules;
- Soft, full capsules.
Soft capsules get their name because during their manufacture, the filler is placed in a still soft elastic shell. The capsules are then subjected to further manufacturing processes, in which the original elasticity of the shell may be partially or completely lost. Such capsules have a whole shell, which can be elastic or rigid. Sometimes the shell of soft capsules contains the active ingredient.
Hard capsules are filled after the entire molding process has been completed, and they have achieved proper elasticity and rigidity. Solid capsules have a two-component structure and can be made in advance, and their filling with biologically active substances is performed as needed.
Currently, the dosage form in the form of gelatin capsules has become very popular among pharmaceutical manufacturers, consumers and doctors due to a number of advantages and positive characteristics. These include, but are not limited to:
- High dosing accuracy of the pharmaceutical substances placed in them. Modern equipment ensures high precision of filling capsules with the 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 dragées, and that their liquid or uncoated solid contents are absorbed faster and easier. Pharmacological action of the drug substance is manifested in 4-5 minutes.
- High stability. Drug substances in capsules are protected from various adverse environmental factors - light, air, moisture, mechanical influences - due to the shell, which provides a sufficiently high tightness and insulation of the components. Therefore, in the manufacture of capsules can avoid the need to use antioxidants or stabilizers or reduce their amount.
- Correcting ability - unpleasant taste and smell of medicinal substances is eliminated.
- High aesthetics - achieved through the use of various dyes in obtaining the capsule shells. Today, leading pharmaceutical companies use up to 1,000 different colors and shades to color the capsule shells.
- The ability to set certain properties for the drugs - creating enteric soluble capsules as well as retard capsules (with prolonged drug release), which can be achieved by various technological methods.
- Fewer excipients are used in the capsule production than, for example, in the production of tablets.
In addition, the capsules require less machinery due to fewer production steps and fewer techniques used than in the production of tablets.
In soft and hard capsules, drugs can be encapsulated in their unmodified form without the wet granulation, heat, and pressure as in tablet production. In addition, the number of factors affecting the release and absorption of drugs from capsules is much lower than for other dosage forms.
The disadvantage of gelatin capsules is their high sensitivity to moisture, which requires compliance with certain conditions of their storage. Another disadvantage is the fact that gelatin is an excellent breeding ground for microorganisms. This drawback is prevented by adding preservatives to the mass: nipagin (0.4%), nipazole (0.4%), sorbic acid (0.1-0.2%), etc.
Hard gelatin capsules, also known as hard-shell gelatin capsules or two-piece capsules, are solid dosage forms in which one or more medicinal agents and/or inert materials are enclosed within a small shell. They are a well-established dosage form, that provides solutions to many of today’s drug delivery and nutraceutical formulation challenges.
A hard gelatin capsule shell consists of two prefabricated, cylindrical sections (a cap and a body) each of which has one rounded, closed-end and one open end. The body has a slightly lower diameter, than the cap, and fits inside the cap.
Hard gelatin capsule shells are fabricated and supplied empty to the pharmaceutical industry by shell suppliers, and then filled in a separate operation. During the capsule filling unit operation, the body is filled with the drug substances, and the shell is closed by bringing the bod,y and the cap together.
Components of hard gelatin capsules.
Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it may contain materials such as plasticizer, colourants, opacifying agents, and preservatives, which either enable capsule formation or improve their performance. Hard gelatin capsules also contain 12–16% water, but the water content can vary, depending on the storage conditions.
Capsule sizes and shapes.
Empty hard gelatin capsule shells come in a variety of sizes ranging from an arbitrary numbering of 000 to 5 with 000 being the largest size and 5 being the smallest. The shape has remained virtually unchanged since its invention, except for the development of the self-locking capsule during the 1960s when automatic filling and packaging machines were introduced.
The size of hard gelatin capsule selected for use is determined by requirements of the formulation, including the dose of the active ingredient and the density and compaction characteristics of the drug and other components. The first step to estimating the optimal capsule size for a given product is to determine the density of the formulation using tapped density for powders and bulk density for pellets, minitablets, and granules. The appropriate capsule size may then be calculated using the measured density of the formulation, the target full weight, and capsule volume. The fill weight for liquids is calculated by multiplying the specific gravity of the liquid by the capsule body volume multiplied by 0.9.
To accommodate special needs, some intermediate sizes (‘elongated sizes’) are produced. These capsule sizes typically have an extra 10% of fill volume compared to the standard sizes e.g. elongated size 00 capsules (00el), elongated size 0 capsules (0el), elongated size 1 capsules (1el), elongated size 2 capsules (2el) etc. The table below shows capsule volumes and typical fill weights for formulations with different tapped densities.
Capsule volumes and typical fill weights for formulations with different tapped densities.
Step 1: Preparation of the gelatin solution (dipping solution)
A concentrated solution of gelatin is prepared by dissolving the gelatin in demineralized water, which has been heated to 60–70 °C in jacketed pressure vessels. This solution contains 30 – 40% w/w of gelatin and is highly viscous, which causes bubbles as a result of air entrapment. The presence of these bubbles in the final solution would yield capsules of inconsistent weight and would also become problematic during capsule filling and upon storage. To remove the air bubbles, a vacuum is applied to the solution; the duration of this process varies with batch size.
Following the above steps, colourants and pigments are added to attain the desired final capsule appearance. At this stage, other processing aids may be added, such as sodium lauryl sulfate, to reduce surface tension. The solution viscosity is measured and adjusted, as needed, with hot demineralized water to achieve the target specification.
The viscosity of the gelatin solution is a critical parameter, as it affects the downstream manufacturing process and plays a major role in capsule shell wall thickness. After physical, chemical, and microbiological testing, the gelatin is released for capsule production. The gelatin solution is then transferred to temperature-controlled tanks on the dipping machine, where it is fed continuously into the dipping dishes.
Step 2: Dip-coating the gelatin solution on to metal pins (moulds)
Capsule shells are manufactured under strict climatic conditions by dipping pairs (body and cap) of standardized steel pins arranged in rows on metal bars into an aqueous gelatin solution (25 – 30% w/w) maintained at about 50 °C in a jacketed heating pan. Because the moulds are below the gelling temperature, the gelatin begins to form a thin gelatin layer or film on the moulds.
The rows of pins are arranged so that caps are formed on one side of the machine while bodies are simultaneously formed on the opposite side of the machine.
Step 3: Rotation of the Dip-coated pins
Following adsorption of the gelatin solution on to the surface of the pins, the bar containing the pins is removed and rotated several times to evenly distribute the solution around the pins, correct gelatin distribution being critical to uniform and precise capsule wall thickness and dome strength.
Step 4: Drying of the gelatin-coated pins
Once the gelatin is evenly distributed on the mould, a blast of cool air is used to set the gelatin on the mould. At this point, the gelatin is dried, and the pins are then passed through several drying stages to achieve the target moisture content.
Step 5: Stripping and trimming
After the gelatin is dried, the capsule is stripped off the mould and trimmed to the proper length.
Step 6: Joining of the trimmed capsule shell
Once trimmed, the two halves (the cap and body) are joined in the pre-closed position using a pre lock mechanism. At this point, printing is done if needed before packing in cartons for shipping.
Step 7: Printing
After formation, the capsule shells can be printed to improve identification. Printing can be achieved using one or two colours, containing information such as product name or code number, manufacturer’s name or logo and dosage details.
Printing reduces the risk of product confusion by the numerous handlers and users of the product including manufacturers, pharmacists, nurses, doctors, caregivers, and patients.
A hard gelatin capsule shell consists of two prefabricated, cylindrical sections (a cap and a body) each of which has one rounded, closed-end and one open end. The body has a slightly lower diameter, than the cap, and fits inside the cap.
Hard gelatin capsule shells are fabricated and supplied empty to the pharmaceutical industry by shell suppliers, and then filled in a separate operation. During the capsule filling unit operation, the body is filled with the drug substances, and the shell is closed by bringing the bod,y and the cap together.
Capsule shells showing features.
Components of hard gelatin capsules.
Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it may contain materials such as plasticizer, colourants, opacifying agents, and preservatives, which either enable capsule formation or improve their performance. Hard gelatin capsules also contain 12–16% water, but the water content can vary, depending on the storage conditions.
Capsule sizes and shapes.
Empty hard gelatin capsule shells come in a variety of sizes ranging from an arbitrary numbering of 000 to 5 with 000 being the largest size and 5 being the smallest. The shape has remained virtually unchanged since its invention, except for the development of the self-locking capsule during the 1960s when automatic filling and packaging machines were introduced.
The size of hard gelatin capsule selected for use is determined by requirements of the formulation, including the dose of the active ingredient and the density and compaction characteristics of the drug and other components. The first step to estimating the optimal capsule size for a given product is to determine the density of the formulation using tapped density for powders and bulk density for pellets, minitablets, and granules. The appropriate capsule size may then be calculated using the measured density of the formulation, the target full weight, and capsule volume. The fill weight for liquids is calculated by multiplying the specific gravity of the liquid by the capsule body volume multiplied by 0.9.
To accommodate special needs, some intermediate sizes (‘elongated sizes’) are produced. These capsule sizes typically have an extra 10% of fill volume compared to the standard sizes e.g. elongated size 00 capsules (00el), elongated size 0 capsules (0el), elongated size 1 capsules (1el), elongated size 2 capsules (2el) etc. The table below shows capsule volumes and typical fill weights for formulations with different tapped densities.
Capsule volumes and typical fill weights for formulations with different tapped densities.
The sequence of two-piece hard gelatin capsule shell manufacture.
Hard gelatin capsules are manufactured using a dip-coating method, and the various stages involved are as follows:Step 1: Preparation of the gelatin solution (dipping solution)
A concentrated solution of gelatin is prepared by dissolving the gelatin in demineralized water, which has been heated to 60–70 °C in jacketed pressure vessels. This solution contains 30 – 40% w/w of gelatin and is highly viscous, which causes bubbles as a result of air entrapment. The presence of these bubbles in the final solution would yield capsules of inconsistent weight and would also become problematic during capsule filling and upon storage. To remove the air bubbles, a vacuum is applied to the solution; the duration of this process varies with batch size.
Following the above steps, colourants and pigments are added to attain the desired final capsule appearance. At this stage, other processing aids may be added, such as sodium lauryl sulfate, to reduce surface tension. The solution viscosity is measured and adjusted, as needed, with hot demineralized water to achieve the target specification.
The viscosity of the gelatin solution is a critical parameter, as it affects the downstream manufacturing process and plays a major role in capsule shell wall thickness. After physical, chemical, and microbiological testing, the gelatin is released for capsule production. The gelatin solution is then transferred to temperature-controlled tanks on the dipping machine, where it is fed continuously into the dipping dishes.
Step 2: Dip-coating the gelatin solution on to metal pins (moulds)
Capsule shells are manufactured under strict climatic conditions by dipping pairs (body and cap) of standardized steel pins arranged in rows on metal bars into an aqueous gelatin solution (25 – 30% w/w) maintained at about 50 °C in a jacketed heating pan. Because the moulds are below the gelling temperature, the gelatin begins to form a thin gelatin layer or film on the moulds.
The rows of pins are arranged so that caps are formed on one side of the machine while bodies are simultaneously formed on the opposite side of the machine.
Step 3: Rotation of the Dip-coated pins
Following adsorption of the gelatin solution on to the surface of the pins, the bar containing the pins is removed and rotated several times to evenly distribute the solution around the pins, correct gelatin distribution being critical to uniform and precise capsule wall thickness and dome strength.
Step 4: Drying of the gelatin-coated pins
Once the gelatin is evenly distributed on the mould, a blast of cool air is used to set the gelatin on the mould. At this point, the gelatin is dried, and the pins are then passed through several drying stages to achieve the target moisture content.
Step 5: Stripping and trimming
After the gelatin is dried, the capsule is stripped off the mould and trimmed to the proper length.
Step 6: Joining of the trimmed capsule shell
Once trimmed, the two halves (the cap and body) are joined in the pre-closed position using a pre lock mechanism. At this point, printing is done if needed before packing in cartons for shipping.
Step 7: Printing
After formation, the capsule shells can be printed to improve identification. Printing can be achieved using one or two colours, containing information such as product name or code number, manufacturer’s name or logo and dosage details.
Printing reduces the risk of product confusion by the numerous handlers and users of the product including manufacturers, pharmacists, nurses, doctors, caregivers, and patients.
The filling of hard gelatin capsules is an established technology, with equipment available ranging from that for very small-scale manual filling (e.g., Feton capsule filling machine), through intermediate-scale semi-automatic filling to large-scale fully automatic filling. Hard gelatin capsules can also be hand-filled one at a time, as done in a compounding pharmacy. The difference between the many methods available is the way, in which the dose of material is measured into the capsule body.
The basic steps in filling hard gelatin capsules include:
The basic steps in filling hard gelatin capsules include:
- Rectification of capsules (placing empty gelatin capsules on the removable plate with bodies facing downward).
- Separation of caps from bodies.
- Dosing of fill material (The body is filled with the formulation manually using a plastic spatula, and the excess powder is removed).
- Replacement of caps/ closing capsule shells.
- Ejection of filled capsules.
Various types of encapsulation machines are available, and these machines are selected based on:
A loading tray with about 200-300 holes,
A powder tray,
A pin plate with about 200-300 pins,
A sealing plate with a rubber cap,
A lever,
A cam handle with loading tray of about 250 holes on the average,
A hand operated capsule filling machine is capable of producing about 6250 capsules per hour. This machine is used by small scale manufacturers and hospitals for extempore preparations.
As the name implies, semi-automatic encapsulators (semi-automatic capsule filling machines) combine both manual and automatic methods of capsule filling, thus can be said to be partially automated. Its operation is simple, and the equipment meets the hygiene requirements for its use in the pharmaceutical industry.
Its simple design and robust construction (which ensures long life and trouble-free operation), the use of stainless steel and non-corrosive approved materials in the construction of contact parts (which eliminates contamination and facilitates easy cleaning after use) make the machine suitable for filling powders and granular materials in the pharmaceutical and health food industries.
Depending on the design, the following events take place.
Automatic encapsulator is a capsule filling machine that is developed and designed to automatically fill an empty hard gelatin capsule with powders and granules. They are used in the large scale production of capsule.
Automatic capsule filling machines are extremely durable and reliable when it comes to capsule filling and maintenance of the integrity of the filled capsules.
Automatic encapsulator can also work as a complete system of fully automatic capsule filling line by attaching additional equipment as online capsule polishing machine, dust extractor, damage capsule sorter and empty capsule ejector.
- The requirement of the manufacturer/nature of the capsule (hard capsule or soft capsule).
- The quantity of capsule to be manufactured.
- Manual /hand operated capsule filling machine.
- Semi-Automatic capsule filling machine.
- Automatic capsule filling machine.
These type of encapsulators consists of a bed of about 200-300 holes,A loading tray with about 200-300 holes,
A powder tray,
A pin plate with about 200-300 pins,
A sealing plate with a rubber cap,
A lever,
A cam handle with loading tray of about 250 holes on the average,
A hand operated capsule filling machine is capable of producing about 6250 capsules per hour. This machine is used by small scale manufacturers and hospitals for extempore preparations.
Semi-automatic encapsulators.
As the name implies, semi-automatic encapsulators (semi-automatic capsule filling machines) combine both manual and automatic methods of capsule filling, thus can be said to be partially automated. Its operation is simple, and the equipment meets the hygiene requirements for its use in the pharmaceutical industry.
Its simple design and robust construction (which ensures long life and trouble-free operation), the use of stainless steel and non-corrosive approved materials in the construction of contact parts (which eliminates contamination and facilitates easy cleaning after use) make the machine suitable for filling powders and granular materials in the pharmaceutical and health food industries.
Depending on the design, the following events take place.
- The sandwich of cap and body rings are positioned under the rectifier to receive the empty capsule, and the caps are separated from the body by pulling the vacuum from beneath the sings.
- The body rings are then positioned under the foot of the powder hopper for filling process.
- The cap and body rings are rejoined and positioned in front of pins which push the bodies to engage of pins which push the bodies have been filled.
- The plate is then swung aside, and the pins are used to eject the closed capsule.
Automatic capsule filling machines are extremely durable and reliable when it comes to capsule filling and maintenance of the integrity of the filled capsules.
Automatic encapsulator can also work as a complete system of fully automatic capsule filling line by attaching additional equipment as online capsule polishing machine, dust extractor, damage capsule sorter and empty capsule ejector.
The suture soft capsules can hold up to 7.5 ml of substances. The capacity of the machine rollers with which the capsules are formed, filled and sealed is measured in units called minim. In this case, 1 minim = 0.062 ml. The most used cell sizes of the rollers are from 2 to 80 minim. More capacious capsules (up to 120 minim) found use in the perfume industry. Unlike soft seamless capsules, which have a strictly spherical shape, suture capsules can vary in shape and come in: round, oblong, oval and others. Soft capsules encapsulate viscous liquids, oil solutions, paste-like medications that do not interact with gelatin. The contents of the capsules may consist of one or more medicinal substances, possibly with various excipients.
Method of pressing (stamping), or modern modification: rotary-matrix. It is used for the production of soft gelatin capsules, being the most rational for their production in the conditions of industrial production. The principle of the method is to initially produce a gelatin tape (matrix), from which capsules are pressed under the press or on the rolls immediately after filling and sealing. The automated machines that use this method perform all operations with high accuracy (± 3%) and high throughput (3,000 to 76,000 capsules per hour) and are capable of producing capsules of varying shapes, wide capacity and with various filler consistencies (mostly liquid and paste-like).
Pressing method The American engineer R. Scherer suggested replacing the horizontal press with two oppositely rotating drums equipped with matrices. Two continuous gelatin bands, obtained by passing through a system of cooled rollers (rollers), are fed to the rotating drums from opposite sides. There are matrices on the surface of the drums that define half of the shape of the resulting capsules. The gelatin ribbons precisely follow the shape of the matrix, and as the opposing matrix shapes align, the capsule contents are dispensed through the holes in the wedge-shaped device. This type of machine is characterized by high dosing accuracy (± 1%) and high throughput.
Drip method is the youngest method, which first appeared in the 60s (introduced in production by the Dutch company "Interfarm Biussum"). Allows to obtain soft, seamless gelatin capsules of strictly spherical shape. Its principle is to squeeze the shell melt and the liquid filler, which fill the capsule as a result of two-phase concentric flow, under pressure from a concentric tubular nozzle; the capsule is sealed by the natural surface tension of gelatin. The method is quite high-throughput (up to 60 thousand capsules per hour) and accurate (deviations in filler dosing do not exceed ± 3%), but it can only be used to encapsulate low-flow liquid non-aqueous fillers with a rather small upper dosing limit (up to 0.3 ml). However, recent developments by Japanese and Israeli specialists have already made it possible to obtain capsules with a much higher upper dosing limit (up to 0.75 ml).
The drop method of obtaining soft gelatin capsules was first proposed by the Dutch company "Globex". This method is based on the phenomenon of formation of a gelatin drop with simultaneous inclusion of the liquid drug substance in it, which is achieved by using two concentric nozzles The molten gelatin mass 5 flows through a heated pipeline into the gichler unit, which is a conical tubular nozzle, from where the drug is pushed out simultaneously with the supply through a dispensing device, filling the capsule as a result of two-phase concentric flow. The droplets are torn off by the pulsator and enter the cooler, which is a circulating system for forming, cooling and stirring the capsules. The formed capsules fall into the cooled Vaseline oil (14 °C) and undergo circular pulsation, acquiring a strictly spherical shape. The capsules are separated from the oil, washed and dried in special chambers (airflow rate of 3 m/s), which allows rapid removal of moisture from the capsule shell.
Advantages and disadvantages of the drip method. The method is characterized by complete automation, high capacity (28-100 thousand capsules per hour), precision dosing of the drug substance (± 3%), hygiene and economical consumption of gelatin. Despite many advantages, this method cannot be universal. Its use is limited both by the size of capsules, from 300 mg to microcapsules and by the contents (the density and viscosity of the solution must be close to oil). The droplet method is very convenient for encapsulating fat-soluble substances and solutions. Capsules produced by the drip method are easily recognized by the absence of a seam on them.
The production of soft seamless gelatin capsules is based on the physical properties of the gelatin mass. The capsules are formed at the outlet of the capsulator head into which the filler and gelatin mass, heated to a certain temperature, are fed under air pressure The capsule formation head is arranged so that the filler is fed by an inner stream and the gelatin mass by an outer stream. Under the influence of pulsating oil in the head, the stream splits and due to the surface tension of the gelatin mass, the separated part gently takes a spherical shape The formed capsule is gradually frozen in a weak stream of cooled vegetable oil at a low temperature. The amount of filler and gelatin mass is adjusted. This produces capsules with filler masses ranging from 0.05 to 0.3 grams. The frequency of oil pulsation in the head is equal to the number of capsules formed and is stable during the production cycle.
Method of pressing (stamping), or modern modification: rotary-matrix. It is used for the production of soft gelatin capsules, being the most rational for their production in the conditions of industrial production. The principle of the method is to initially produce a gelatin tape (matrix), from which capsules are pressed under the press or on the rolls immediately after filling and sealing. The automated machines that use this method perform all operations with high accuracy (± 3%) and high throughput (3,000 to 76,000 capsules per hour) and are capable of producing capsules of varying shapes, wide capacity and with various filler consistencies (mostly liquid and paste-like).
Pressing method The American engineer R. Scherer suggested replacing the horizontal press with two oppositely rotating drums equipped with matrices. Two continuous gelatin bands, obtained by passing through a system of cooled rollers (rollers), are fed to the rotating drums from opposite sides. There are matrices on the surface of the drums that define half of the shape of the resulting capsules. The gelatin ribbons precisely follow the shape of the matrix, and as the opposing matrix shapes align, the capsule contents are dispensed through the holes in the wedge-shaped device. This type of machine is characterized by high dosing accuracy (± 1%) and high throughput.
Drip method is the youngest method, which first appeared in the 60s (introduced in production by the Dutch company "Interfarm Biussum"). Allows to obtain soft, seamless gelatin capsules of strictly spherical shape. Its principle is to squeeze the shell melt and the liquid filler, which fill the capsule as a result of two-phase concentric flow, under pressure from a concentric tubular nozzle; the capsule is sealed by the natural surface tension of gelatin. The method is quite high-throughput (up to 60 thousand capsules per hour) and accurate (deviations in filler dosing do not exceed ± 3%), but it can only be used to encapsulate low-flow liquid non-aqueous fillers with a rather small upper dosing limit (up to 0.3 ml). However, recent developments by Japanese and Israeli specialists have already made it possible to obtain capsules with a much higher upper dosing limit (up to 0.75 ml).
The drop method of obtaining soft gelatin capsules was first proposed by the Dutch company "Globex". This method is based on the phenomenon of formation of a gelatin drop with simultaneous inclusion of the liquid drug substance in it, which is achieved by using two concentric nozzles The molten gelatin mass 5 flows through a heated pipeline into the gichler unit, which is a conical tubular nozzle, from where the drug is pushed out simultaneously with the supply through a dispensing device, filling the capsule as a result of two-phase concentric flow. The droplets are torn off by the pulsator and enter the cooler, which is a circulating system for forming, cooling and stirring the capsules. The formed capsules fall into the cooled Vaseline oil (14 °C) and undergo circular pulsation, acquiring a strictly spherical shape. The capsules are separated from the oil, washed and dried in special chambers (airflow rate of 3 m/s), which allows rapid removal of moisture from the capsule shell.
Advantages and disadvantages of the drip method. The method is characterized by complete automation, high capacity (28-100 thousand capsules per hour), precision dosing of the drug substance (± 3%), hygiene and economical consumption of gelatin. Despite many advantages, this method cannot be universal. Its use is limited both by the size of capsules, from 300 mg to microcapsules and by the contents (the density and viscosity of the solution must be close to oil). The droplet method is very convenient for encapsulating fat-soluble substances and solutions. Capsules produced by the drip method are easily recognized by the absence of a seam on them.
The production of soft seamless gelatin capsules is based on the physical properties of the gelatin mass. The capsules are formed at the outlet of the capsulator head into which the filler and gelatin mass, heated to a certain temperature, are fed under air pressure The capsule formation head is arranged so that the filler is fed by an inner stream and the gelatin mass by an outer stream. Under the influence of pulsating oil in the head, the stream splits and due to the surface tension of the gelatin mass, the separated part gently takes a spherical shape The formed capsule is gradually frozen in a weak stream of cooled vegetable oil at a low temperature. The amount of filler and gelatin mass is adjusted. This produces capsules with filler masses ranging from 0.05 to 0.3 grams. The frequency of oil pulsation in the head is equal to the number of capsules formed and is stable during the production cycle.
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