Manufacturing of medical capsules and microcapsules

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Manufacturing of medical capsules and
microcapsules
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Plan

1. Characteristic of capsules as dosage forms.
2. Manufacturing of Hard Gelatin Shells (capsules).
3. Hard-Gelatin Capsule filling.
4. Soft-Gelatin Capsules.
5. Microcapsules.

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• Capsules are solid dosage forms with hard or soft
  shells. They are of various shapes and sizes, and
  contain a single dose of one or more active
  ingredients. They are intended for oral
  administration.
• In capsules the drug is enclosed within hard or
  soft shell.

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• Capsule shells are made of gelatin or other
  substances, the consistency of which may be
  modified by the addition of substances such as
  glycerol or sorbitol.
• The shell should disintegrate in the presence of
  digestive fluids so that the contents are
  released.
• The contents should not cause deterioration of
  the shell.

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Excipients for production of the Capsule shells

• diluents,
• solvents,
• surface-active substances,
• opaque fillers,
• antimicrobial agents,
• sweeteners,
• colouring matter,
• flavouring substances,
• disintegrating agents,
• glidants,
• lubricants,
• substances capable of modifying the behaviour of
  the active ingredient(s) in the gastrointestinal
  tract.

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Categories of capsules

• hard capsules
• soft capsules (softgels)
• modified-release capsules
• delayed-release capsules (gastroresistant /
  enteric capsules)
• sustained-release capsules
• (extended-/prolonged release capsules).

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Type of capsules depend on plasticizer content
and technological principle

• 1. Hard-Shell Gelatin Capsules
• 2. Soft- Gelatin Capsules (softgels)

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Soft gelatin capsules (softgels) are hermetically
sealed one-piece capsules containing a liquid or
a semisolid fill.Soft capsules are usually
formed, filled, and sealed in one operation.
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Advantages of soft-gelatin capsules

• Improved bioavailability, as the drug is
  presented in a solubilized form.
• Enhanced drug stability.
• Consumer preference regarding ease of swallowing,
  convenience, and taste can improve compliance.
• Offer opportunities for product differentiation
  via colour, shape, and size and product line
  extension.
• The softgels can be enteric coated for delayed
  release.
• They are popular for pharmaceuticals, cosmetics,
  and
• nutritional products.

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• Hard capsules have shells consisting of two
  prefabricated cylindrical sections that fit
  together.
• One end of each section is rounded and closed,
  and the other is open. The contents of hard
  capsules are usually in solid form (powder or
  granules).

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In the manufacture of capsules, measures are
taken to

• ensure that the active ingredient(s) when present
  in solid state form have appropriate solid-state
  properties such as particle-size distribution and
  polymorphic form
• ensure that mixing with excipients is carried out
  in a manner that ensures homogeneity
• minimize the degradation of the active
  ingredient(s)
• minimize the risk of microbial contamination
• minimize the risk of cross contamination.

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Stage of capsules production

1. Preparing of gelatin solutions.
2. Preparing of gelatin shells.
3. Hard-gelatin capsule filling.
4. Packing and labeling.

1. Preparing of gelatin solutions.
2. Preparing and filling of soft-gelatin capsules.
3. Packing and labeling.

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HJ Series Gelatin Melting Tank
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Obtaining of gelatin solutions with stage of
swelling

1. Swelling of gelatin in cold water (15 - 18 C,
   1.5 - 2 hours).
2. Dissolving of gelatin.
3. Adding preservatives, plasticizers and others
   excipients.
4. Remove of air bubbles from the solution of the
   gelatin by the vacuum.
5. Stabilization of solution of the gelatin (45-60
   C).

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Obtaining of gelatin solutions without stage of
swelling

1. Heating of purified water (70-75 C).
2. Dissolution of preservatives, plasticizers and
   others excipients in the water.
3. Dissolution of the gelatin.
4. Remove of air bubbles from the solution of the
   gelatin by a vacuum.
5. Stabilization of the solution of the gelatin
   (45-60 C).

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Droplet method

• 1. Container with medicines substance
• 2. Hoper with medicines substance
• 3. Container with gelatin solution
• 4. Conical nozzle
• 5. Pulsater
• 6. Cooler
• 7. Container with Vaseline oil

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Characteristic of Droplet method

• It is based on formation of spherical gelatinous
  drop filled with a solution or suspension of
  medicinal substance at simultaneous drop dosage
  of medicinal substance solution followed by
  subsequent cooling of heated gelatinous mass in
  cool liquid petrolatum. As the result joinless
  spherical gelatious capsule with elastic shell is
  formed.

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Droplet method

• 1. Container with medicines substance
• 2. Hoper with medicines substance
• 3. Container with gelatin solution
• 4. Conical nozzle
• 5. Pulsater
• 6. Cooler
• 7. Container with Vaseline oil

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RG2-200 250 300 Series Soft Gelatin Encapsulation
Machine

• For volume-production, increase the utilization
  ration of gelatin skin
• convey gelatin skin with a plane surface more
  steady running condition
• oil saving
• suitable for volume-production, continually for
  24 hour.
• (Huizhou Pingfang pharmaceutical machinery co.
  ltd.)

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Pressing method

• Preparing of an initial gelatinous tape, placing
  it into metal plates and rolls having deepening
  holes resembling half of the capsules.
• While heating gelatin fills this mould. Drug is
  fed into a hollow in a gelatinous tape, then this
  half of a capsule is joined with another one
  formed and filled in the same way. Obtained
  capsules have a horizontal weld.

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Pressing (rotate die) method

• The glycerol gelatin solution is heated and
  pumped onto two chilled drums-1 to form two
  separate ribbons-2, which form each half of the
  softgel.
• The ribbons are lubricated and fed into the
  filling machine, forcing the gelatin to adopt the
  contours of the die.
• The fill-4 is manufactured in a separate process
  and pumped in, and the softgels are sealed by the
  application of heat and pressure.
• Once cut from the ribbon (5), they are tumble -
  dried and conditioned at
• 20 relative humidity.

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Hard capsules production

• To manufacture the shells, pairs of molds, for
  the body and the cap, are dipped into an aqueous
  gelatin solution (25 30 w/w), which is
  maintained at about 50 C in a jacketed heating
  pan.
• As the pins are withdrawn, they are rotated to
  distribute the gelatin evenly and blasted with
  cool air to set the film.
• Drying is carried out by passing dry air over the
  shell as heating temperatures are limited due to
  the low melting point of gelatin.
• The two parts are removed from the pins, trimmed,
  and joined using a prelock mechanism.

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SFR 901 FS6/7

• In this model of capsule making machine, dipping
  action, transfer along upper deck, transfer from
  upper to lower deck and transfer from lower deck
  to table are all performed by high precision
  programmable servo motors combined with precision
  ball screws

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Hard - Gelatin Capsule Filling

• Powders and granules are the most common filling
  materials for hard - shell gelatin capsules,
  although pellets, tablets, pastes, oily liquids,
  and nonaqueous solutions and
• suspensions have been used.
• Filling machines are differentiated by the way
  they measure the dose of material and range in
  capacity from bench - top to high - output,
  industrial, fully automated machines.

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Hard - Gelatin Capsule Filling

• Most automated machinery is of the independent
  type and compresses a controlled amount of powder
  using a low compression force (typically 50 200
  N ) to form a plug. Most are piston - tamp
  fillers and are dosator or dosing disk machines.
• The powder is passed over a dosing plate
  containing cavities slightly smaller than the
  capsule diameter, and powder that falls into the
  holes is tamped by a pin to form a plug.

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• In the dosator method, the plug is formed within
  a tube with a movable piston that controls the
  dosing volume and applies the force to form the
  plug.
• The dose is controlled by the dimensions of the
  dosator, the position of the dosator in the
  powder bed, and the height of the powder bed.

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NJP-3000,3500 series automatic capsule filling
machine

• It comply with volume-produce.
• This machine adopts full sealed filling and
  turret parts and easy to clean,
• upper and lower die assemblies move in one-way,
  imported double-lip sealing ring made of
  polyurethane and have high performance,
• die assemble cleaning work station combine
  blowing and breathing to ensure no powder in die
  hole during high speed running,
• there is no absorb device in locking work
  station, lubricant be added timing in
  transmission work station.

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Modified-release capsules

• They are hard or soft capsules in which the
  contents or the shell or both contain excipients
  or are prepared by special procedures such as
  microencapsulation which, separately or together,
  are designed to modify the rate, place or time of
  release of the active ingredient(s) in the
  gastrointestinal tract.

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• Sustained-release capsules
• (Extended- or Prolonged-release capsules) are
  designed to slow the rate of release of the
  active ingredient(s) in the gastrointestinal
  tract.
• Delayed-release capsules
• (gastro-resistant/enteric capsules) are hard or
  soft capsules prepared in such a manner that
  either the shell or the contents resist the
  action of gastric fluid but release the active
  ingredient(s) in the presence of intestinal
  fluid.

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Microcapsule is a small sphere with a uniform
wall around it.

• Micro-encapsulation is a process in which tiny
  particles or droplets are surrounded by a coating
  to give small capsules many useful properties.
• The material inside the microcapsule is referred
  to as the core, internal phase, or fill, whereas
  the wall is sometimes called a shell, coating, or
  membrane.
• Most microcapsules have diameters between a few
  micrometers and a few millimeters.

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The reasons for microencapsulation

• In some cases, the core must be isolated from its
  surroundings, as in isolating vitamins from the
  deteriorating effects of oxygen,
• retarding evaporation of a volatile core,
• improving the handling properties of a sticky
  material, or isolating a reactive core from
  chemical attack.
• In other cases, the objective is not to isolate
  the core completely but to control the rate at
  which it leaves the microcapsule, as in the
  controlled release of drugs or pesticides.
• The problem may be as simple as masking the taste
  or odor of the core, or as complex as increasing
  the selectivity of an adsorption or extraction
  process.

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