Capsules are a solid dosage form enclosed in a hard shell or soft gelatin coating. When taken with water, the capsules’ coating becomes slippery and easy to swallow.
i) Hard Gelatin Capsule
It is a solid dosage form in which medications are encapsulated in a two part empty hard gelatin capsule shell.
The upper and small part is called ‘CAP’ and the remaining large part is called ‘BODY’.
There are 8 different sizes of capsule shell(000,00,0,1,2,3,4,5) with different fill volume.
Normally 0 and 2 sized shells are widely used.
The shell of hard gelatin capsules basically consists of gelatin, plasticizers and water.
Modern day shells may, in addition, consist of preservatives, colours, opacifying agents, flavours, sugars, acids, enteric materials etc.
The gelatin is marketed in a large number of varieties and a specific quality and gelatin having specified gel strength, viscosity, iron content etc. should be selected for capsules.
The variations in gelatin properties arise because of changes in molecular weights and methods followed in conversion into gelatin.
There are two filling process:
• Pellet filling
• Granules filling
Problems occurred during encapsulation:
1. Blank shell
2. Shell lock in channel
3. Shell breaking
4. Improper filling of shell
5. Improper fitting of shell in dies if compressed air pressure is not adjusted properly.
6. Improper or large size of pellets may cause blockage of nozzle. So shells are left empty.
1. Automatic Capsule Filling machine
Capacity: 65000 capsule/hour
Made in China
3. Semi automatic capsule filling machine
Process of Gelatin Capsule Manufacture
ii) Soft Gelatin Capsule
A softgel (or a soft gelatin capsule) is a solid capsule (outer shell) surrounding a liquid or semi solid center (inner fill).
An active ingredient can be incorporated into the outer shell, the inner fill, or both.
These capsules are available in a variety of shapes, the common shapes being spherical, oblong and elliptical.
Size wise also the range is bigger and capsules of capacities ranging from 0.1 ml to 30 ml are used.
The composition of soft gelatin capsule shells is similar to the hard gelatin capsules except that a larger proportion of plasticizer is incorporated to make them soft and elastic.
The outer shell is composed of a gelatin or potato starch matrix. Gelatin matrix consists of gelatin, plasticizer, solvent and optional ingredients such as flavors and colorants.
Gelatin – Bovine, porcine, or piscine (fish) origin. Comes in a variety of bloom strengths, the higher the bloom strength, the more resilient the gel. Most oil based fills are encapsulated using a bloom strength of 150. When polyethylene (PEG) based fills are used, a higher bloom strength is generally used.
The limitations of bovine (i.e. bovine-related diseases) and porcine (i.e. not kosher) gelatin may be overcome by piscine (fish) gelatin.
Plasticizer – Glycerin and Sorbitol Special are the two most common plasticizers. Glycerin is generally used with oil based fills. Sorbitol Special is used with PEG based fills. Sorbitol is not soluble in PEG and therefore will not leach out of the shell into the PEG base fill like Glycerin would. Sorbitol Special is formulated to inhibit sorbitol from crystallizing out in the gelatin shell. Do not substitute Sorbitol for Sorbitol Special.
Optional Ingredients -Colors
Avoid aldehydes which can lead to cross linking (pellicle formation) of the gelatin, and poor dissolution of the gelatin capsule in water. This may be overcome by adding enzymes to the dissolution media, (see FDA Guidelines)
Drugs sensitive to water can degrade (e.g. ranitidine) or undergo polymorphic conversion (e.g. terazosin).
Compounds (especially those of high water solubility) can migrate from the fill into the shell or get trapped in a hydrophobic matrix resulting in poor dissolution and loss of bioavailability.
Soft Gelatin Encapsulation Processes and Equipment
Rotary Die process
Two ribbons of gelatin are fed continuously into a rotating die assembly and are simultaneously formed into the two halves of a capsule. The ribbons converge adjacent to a fill injector. The fill injector is actuated by a pump which measures and dispenses the appropriate volume of fill material into the capsules. The filled capsules are subsequently sealed as the die assembly rotates. This process permits accurate and reproducible fill uniformity.
Pump heads are available for fill weights as low as 100 mg. For oral dosage forms, the fill weight ranges from 100 mg up to about 1 gram.
The following should be monitored/controlled:
1. Gelatin temperature
2. Fill temperature
3. Ribbon thickness
4. Seal or seam width
5. Fill quantity
Following encapsulation, the capsules undergo drying in a tumble drying tunnel with an elevated temperature and a large volume of forced air. From the drying tunnel, the capsules are transferred onto trays and placed into a low humidity drying room. Drying is a dynamic process, and the goal is to have the gelatin shell return to its equilibrium moisture content in the range of 6 – 8%.Oil fills dry faster than PEG fills, and typically reach a shell moisture content of 6 to 8% within 24 hours.
Soft gelatin capsules are generally manufactured by the plate or the rotary die process.
In the plate process a sheet of soft gelatin is placed on a plate having a number of dies and the sheet is drawn into the dies by application of vacuum. The material is then filled in and another sheet of gelatin overlaid. Then a die press descends which seals and cuts out the capsules. This process can, at best, be considered to be semi-automatic.
The rotary die machines, of which several versions are now in the market, operate on a continuous basis and are suitable for large scale manufacture. In rotary machine two continuous gelatin sheets are produced on two rotating drums and are conveyed to two cylinders with matching dies rotating in the same direction. As the gelatin sheets come between the dies the material to be filled is injected through a metering device causing the sheet to swell up and form capsules. Simultaneously the pressure exerted by converging di8es seal and cuts out the capsules. The finished capsules, which fall on a conveyor belt, are carried through rapid dryers, where a greater part of the moisture goes off. The remaining moisture is removed by passing capsules through drying channels into which air is passed under pressure. Most of the early machines could fill liquid preparations only. Recently Accogel or Stern machines capable of filling powders as well have been marketed by Lederle Laboratories.
Process flow chart: (Soft gelatin capsule manufacturing)
1. Handbook of Pharmaceutical Granulation Technology (Dilip M. Parikh)
2. Encyclopedia of Pharmaceutical Technology (James Swarbrick – Taylor and Francis)
3. The Theory and practice of Industrial Pharmacy, (Leon. Lachman, H.A. Lieberman, J.L. Kanig)