Capsules are solid unit dosage forms in which the drug substance is enclosed within either a hard or soft gelatin shell.
Hard gelatin capsules (HGC):
I) GELATIN is obtained by animal bones, connective tissues and collagen. The gelatin polypeptide chain upon hydrolysis yields 18 amino acids amongst which glycine and alanine are present in major amount.
Depending upon the source of collagen and manner of extraction, chemical and physical properties of gelatin can vary.
There are two types of gelatin:
A) Type A: It is obtained by acid hydrolysis of tissues. Iselectric pH: 9.
B) Type B: It is obtained by alkali hydrolysis of tissues. Isoelectric pH: 4.7.
II) Opacifying agents are added in the capsule shells to protect the drug from light or to conceal the content. Example: titanium dioxide.
III) Preservatives are added to prevent microbial growth. Example: methyl paraben and propyl paraben.
IV) Lubricant: less than 2%.
V) Moisture content: Finished hard gelatin capsules contain equilibrium moisture content of 12-15%. It is determined by toluene distillation method.
This moisture content is critical to maintain physical properties of the shell as moisture content < 12% causes gelatin to form brittle film and moisture content > 18% causes softening of shells.
It is necessary to avoid extreme temperatures hence capsules are kept in relative humidity 40-60% and temperature 21-24°C during handling and sorting.
Advantages of HGC:
Powder or granules are directly filled into capsule shells. No compression is applied to the components like in tablets.
Capsule shell dissolves rapidly in stomach and releases content rapidly.
Disadvantages of HGC:
Highly soluble salts like iodide, bromide, chloride are generally not dispensed in HGC. Their rapid release in stomach causes gastric irritation due to high concentration of salt in localised area.
Solubility limits of empty capsules:
In evaluation of capsules following terms are used:
Soft spot: the site at which capsule lie next to the tray or other capsule, dries slowly. This is called soft spot.
Bloating: If capsules are stored at high humidity (60%) then capsule size enlarges (bloating).
Foreign capsule: unfilled capsules.
In soft gelatin capsules drug is either dissolved, dispersed or suspended in a vehicle and encapsulated.
When a drug suspension os to be filled in SGC, lecithin is used as wetting agent.
A) Gelatin shell is plasticised by using plasticizers like sorbitol, glycerin, propylene glycol.
The ratio of dry plasticizer to dry gelatin measures the hardness of the capsule shells.
Dry wt of plasticizer/dry wt of gelatin = Hardness of gelatin shell.
The basic gelatin formulation from which plasticized films are usually prepared consists of one part of gelatin, one part of water and 0.6-0.8 parts of plasticizer.
This will be the gelatin shell with moisture content 6-10%.
B) Preservatives: are used in the concentration of 0.2%.
These are often used as a combination of methyl paraben (4 parts) and propyl paraben (1 part).
C) Opacifier: e.g. titanium dioxide (0.2-1.2% conc.)
D) Other additives for capsule shell:
Fumaric acid(1%): to increase the acid solubility.
Sugar (5%): to impart taste and to produce chewable shells.
Essential oils (2%): for odor and taste.
Disadvantages of SGC:
1. There is a close contact between gelatin shell and liquid content which increases the chances of interaction. E.g. chloral hydrate causes proteolysis of gelatin shell when formulated with oily vehicle.
2. As gelatin shell has some concentration of moisture, drugs can migrate from liquid vehicle to the gelatin shell depending upon partition coefficient of drug.
3. Liquid pH should be between 2.5-7.5. Liquids with more acidic pH hydrolyse of shell and leakage. More basic liquids and aldehyde cause tanning of gelatin making it insoluble in gastric pH.
4. Aqueous emulsions cannot be encapsulated in SGC as water in it may affect the integrity of gelatin shell.
Hard gelatin capsules (HGC):
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| Hard Gelatin Capsules |
- Contain two parts: a cap and other is a body.
- Widely used for the filling of powders, granules and pellets.
- Manufactured by dipping method, which involves steps: Dipping, Rotation, Drying, Stripping, Trimming & Joining.
- These are less plasticised than soft gelatin capsules.
Soft gelatin capsules ( SGC):
 |
| Soft Gelatin Capsules (Softgels) |
- Referred as softgels as these are made from the more plasticised gelatin film.
- These are completely sealed dosage form & cannot be opened without destroying the shell.
- Generally, suspensions or the solutions of drug that do not solubilize the gelatin shell are enclosed in SGC.
- The most common methods for preparation of SGC is Rotary die process, Plate process, Bubble method, Accogel (powder or granules filling).
HARD GELATIN CAPSULES ( HGC)
I) GELATIN is obtained by animal bones, connective tissues and collagen. The gelatin polypeptide chain upon hydrolysis yields 18 amino acids amongst which glycine and alanine are present in major amount.
Depending upon the source of collagen and manner of extraction, chemical and physical properties of gelatin can vary.
There are two types of gelatin:
A) Type A: It is obtained by acid hydrolysis of tissues. Iselectric pH: 9.
B) Type B: It is obtained by alkali hydrolysis of tissues. Isoelectric pH: 4.7.
II) Opacifying agents are added in the capsule shells to protect the drug from light or to conceal the content. Example: titanium dioxide.
III) Preservatives are added to prevent microbial growth. Example: methyl paraben and propyl paraben.
IV) Lubricant: less than 2%.
V) Moisture content: Finished hard gelatin capsules contain equilibrium moisture content of 12-15%. It is determined by toluene distillation method.
This moisture content is critical to maintain physical properties of the shell as moisture content < 12% causes gelatin to form brittle film and moisture content > 18% causes softening of shells.
It is necessary to avoid extreme temperatures hence capsules are kept in relative humidity 40-60% and temperature 21-24°C during handling and sorting.
Advantages of HGC:
Powder or granules are directly filled into capsule shells. No compression is applied to the components like in tablets.
Capsule shell dissolves rapidly in stomach and releases content rapidly.
Disadvantages of HGC:
Highly soluble salts like iodide, bromide, chloride are generally not dispensed in HGC. Their rapid release in stomach causes gastric irritation due to high concentration of salt in localised area.
Solubility limits of empty capsules:
- Water resistance: Fails to dissolve in water at 20-30°C in 15 minutes.
- Acid solubility: Dissolves in less than 5 minutes in 0.5% aqueous HCl at 36-38°C.
In evaluation of capsules following terms are used:
Soft spot: the site at which capsule lie next to the tray or other capsule, dries slowly. This is called soft spot.
Bloating: If capsules are stored at high humidity (60%) then capsule size enlarges (bloating).
Foreign capsule: unfilled capsules.
SOFT GELATIN CAPSULES (SGC)
In soft gelatin capsules drug is either dissolved, dispersed or suspended in a vehicle and encapsulated.
When a drug suspension os to be filled in SGC, lecithin is used as wetting agent.
A) Gelatin shell is plasticised by using plasticizers like sorbitol, glycerin, propylene glycol.
The ratio of dry plasticizer to dry gelatin measures the hardness of the capsule shells.
Dry wt of plasticizer/dry wt of gelatin = Hardness of gelatin shell.
0.4/1= Hard
0.6/1= Medium
0.8/1= Soft
The basic gelatin formulation from which plasticized films are usually prepared consists of one part of gelatin, one part of water and 0.6-0.8 parts of plasticizer.
This will be the gelatin shell with moisture content 6-10%.
B) Preservatives: are used in the concentration of 0.2%.
These are often used as a combination of methyl paraben (4 parts) and propyl paraben (1 part).
C) Opacifier: e.g. titanium dioxide (0.2-1.2% conc.)
D) Other additives for capsule shell:
Fumaric acid(1%): to increase the acid solubility.
Sugar (5%): to impart taste and to produce chewable shells.
Essential oils (2%): for odor and taste.
Disadvantages of SGC:
1. There is a close contact between gelatin shell and liquid content which increases the chances of interaction. E.g. chloral hydrate causes proteolysis of gelatin shell when formulated with oily vehicle.
2. As gelatin shell has some concentration of moisture, drugs can migrate from liquid vehicle to the gelatin shell depending upon partition coefficient of drug.
3. Liquid pH should be between 2.5-7.5. Liquids with more acidic pH hydrolyse of shell and leakage. More basic liquids and aldehyde cause tanning of gelatin making it insoluble in gastric pH.
4. Aqueous emulsions cannot be encapsulated in SGC as water in it may affect the integrity of gelatin shell.
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