14: Capsules

capsules

solid dosage forms in which one or more medicinal agents, with or without inert substances, are enclosed in either a hard or a soft, soluble container or shell generally prepared from a suitable form of gelatin

how is gelatin made?

made from the bones of animals

Unique Properties

Although development work has been done on the preparation of capsules from methylcellulose and calcium alginate, gelatin because of its unique properties remains the primary composition material for the manufacture of capsule shells.

**Hydroxypropyl Cellulose

advantages of capsule dosage form

-tasteless- masks taste of unpleasant substances
-easily administered oral dosage form
-easily compounded- extemporaneously prepared or manufactured on an industrial scale
-drug combination
-drug is more bioavailable
-protection from light
-placebo therapy

disadvantages of capsule dosage forms

- divided dose flexibility
- some drugs can not be put into gelatin (salts, hydroscopic, deliquescent, and efflorescent drug)
- high dose administration of capsules- gelatin capsules may stick together in stomach
- tampering
- expensive

gelatin

- available as fine powder, course powder, shreds, flakes or sheets
- obtained from collages material by hydrolysis
- extract of collagenous tissues is proteinaceous in nature essentially composed of glycine, glutamic acid and prolines

what are the two types of gelatin?

Type A and Type B (Pharmagel)

gelatin type A

- it is derived from pork skin by acid processing (1-5% HCl)
- is lighter in color compared to type B

gelatin type B

- it is obtained from bones and animal skins by alkaline processing
- darker in color (because of calcium)

low molecular weight=

high viscosity

high molecular weight=

low viscosity

properties of gelatin

- gelatin contains some moisture which varies between 8 to 12%
- stable in air when dry
- prone to microbial decomposition when it becomes moist
- almost insoluble in cold water
- soluble in hot water and in warm gastro-intestinal fluids

types of capsules

hard gelatin and soft gelatin

what may be filled in capsules?

- powders
- granulates, pellets, beads, etc
- liquids (oils, non-aqueous solutions, suspensions)
- semi-solid masses (ointments, creams, pastes, gels)

*Absolutely NO water or preparations containing water

hard gelatin capsules

consists of two sections, one slipping over the other, thus completely surrounding the drug or drug formulation

These capsules are filled by introducing the powdered material into the long end or body of the capsule and then slipping on the cap.

when humidity is low

the capsules may be lose moisture to atmosphere and thereby become brittle

when humidity is high

the capsules soften become flaccid and lose their shape

High temperatures can also adversely affect the capsules

the largest size of a capsule

is no. 000

the smallest size of a capsule

is no 5

hard shell capsule composition

- gelatin (pharmagel A or B)
- sucrose (shell hardness)
- sulfur dioxide (as bleach and for transparency)
- water
- colorant (optional) and/or opacifier (optional)

rule of 6's

Capsule number + weight of powder (gr) = 6; convert weight of powder to milligrams
1 gr = 65 mg

Capsule diluent: dicalcium phosphate

- may retard dissolution rate of the drug
- incompatible with tetracycline

Water soluble

Capsule diluent: kanolin

good for eutectic mixture

Capsule diluent: lactose

incompatible with amines

Capsule diluent: magnesium carbonate

good for eutectic mixtures

Capsule diluent: magnesium oxide

- alkaline in nature; incompatible with acidic drugs
- good for eutectic mixtures

glidants

the substances that improve flow of powder material

• colloidal silicone dioxide

• magnesium stearate/sodium lauryl sulfate

  • water-proofing characteristics

  • wetting agent

    • Sodium Lauryl Sulfate

• Talc

preparation of filled hard gelatin capsules

- developing and preparing the formulation and selecting appropriate capsule size
- filling the capsule size
- cleaning and polishing the filled capsule

capsule filling

- small scale: punching method, hand-operated capsule-filling machine
- large scale: semi-automatic encapsulation machines, fully automatic encapsulation machines

extemporaneous filling- "punching"

- weigh and mix ingredients by trituration. reduce to a fine and uniform powder
- place powder on paper and arrange it in a uniform pile of a depth of about 1/3 of the length of the capsule
- repeatedly press the open end of the body of the capsule downward into the powder pile until capsule is filled
- place cap on capsule body and weigh

coni-snap

1. tapered rims -avoid telescoping
2. indentations- prevent premature of accidental opening
3. grooves- lock the two capsule parts (body and cap) together

soft gelatin capsules

• consists of soft, globular gelatin shell which is somewhat thicker than that of hard shell capsules

• plasticized by the addition of glycerin, sorbitol or similar polyol which provide the capsules flexibly and elasticity and thereby durability

• Since these capsules contain moisture slightly higher in composition than hard shell capsules, these contain a preservative (methy- and propyl parabens and sorbic acid) to contain growth of fungi.

Soft Gelatin Capsules seals and shapes

Seals

• Unlike in the case of hard shell capsules which consist of body and a cap, soft shell capsules are hermetically sealed and have seam at the point of closure.

• Oral soft gelatin capsule dosage forms generally are made so that the heat - sealed seam of the gelatin shell opens to release its liquid medication into the stomach less than 5 minutes after ingestion.

• When used as suppositories, it is the moisture present in the body cavity that causes the capsule to come apart at its heat - sealed seam and to release its contents.

Shapes

• Variety of shapes and sizes

• Most often used for liquids or mixtures of liquids

• Capsule shape - depends of route

  • Oral, rectal, vaginal, and specialty form for topical, ophthalmic, otic

• Can not be prepared extemporaneously in pharmacy

the capsule shell is basically composed of

• gelatin, a plasticizer and water (to make the soft gelatin shell elastic and pliable) and water.

• preservative, coloring and opacifying agents, flavoring and sugars for desired effects

soft shell capsules composition

- gelatin (pharmagel A or B of lower bloom strength)
- plasticizer to impart flexibility and elasticity, and therefore durability (e.g., glycerin, sorbitol, polyol)
- preservative (e.g., β-naphthol, methyl and propyl parabens, sorbic acid, etc.)
- water (slightly more than hard shell capsules)
- colorants (optional)

what are the main vehicle classes for soft-gelatin capsules?

• water-immiscible

• water-dispersible

• water-miscible

basis for vehicle selection

- compatibility
- stability
- effect on bioavailability

preparation of soft gelatin capsules

- requirements of filling solution
- suitable solvents are needed
- limitations (water)
- manufacturing (plate process, rotary die process)

Application of Soft Gelatin Capsules

Liquids

- water-immiscible, volatile and non-volatile liquids (vegetable and aromatic oils)
- water miscible, non-volatile liquids (PEGs)
- water- miscible and relatively non-volatile

Others

• Ointments, creams, pastes, gels, powders, etc.

vegicaps

• plant origin and are an alternative to gelatin capsules for those who prefer an animal-free product

• the hard shell is made from hydroxypropyl methylcellulose or methylcellulose

• soft shell is made from seaweed extract and gluten free starch, and contains no modified sugars or artificial ingredients.

• The shells can be clear or colored, and there is a wide range of shapes, sized and colors available.

v caps

two piece capsules made of hydroxypropyl methylcellulose, a cellulose-based raw material. gluten-free, vegan, kosher, and halaal

Licaps

two piece capsules made of gelatin or hydroxypropyl methylcellulose designed specially to contain liquids or semi-solids

Licaps can be used when drugs’ ingredients when drugs’ ingredients are more stable as a liquid, such as in dietary supplements. They may not meet restrictive dietary needs because of gelatin content.