DRUG DOSAGE FORMS & DELIVERY SYSTEMS


Types of Capsules

Capsules are solid dosage forms in which the drug is enclosed within either a hard or soft soluble container or “shell”.

They are usually formed from gelatin; however, they also may be made from starch or other suitable substances.

HARD SHELL CAPSULES
  • Available from 000 (largest) to 5 (smallest)
  • Larger bolus capsule: Veterinary use in large animals
  • Size 0 is usually the largest capsule size used orally for humans
  • Size 000 are sometimes used to encapsulate the medication for rectal or vaginal use.
  • The capsule should be moistened with lubricating jelly or water before insertion
Capsule sizes and capacity
Capsule Range of powder capacity
No. 5 60-130mg
No. 4 95-260mg
No. 3 130-390mg
No. 2 195-520mg
No. 1 225-650mg
No. 0 325-910mg
No. 00 390-1300mg
No. 000 650-2000mg
Types of Gelatin Capsules
  1. Hard Gelatin Capsules
    — also called Telescoping Capsules or Dry Filled Capsules
  2. Soft Gelatin Capsules
    — also referred to as “Pearls”
    — also made from shells of gelatin except for the addition of glycerin or any polyhydric alcohol (sorbitol), which renders the shells more elastic or plastic like.


Manufacturing of Capsules

Method of Production of the Hard Gelatin Capsules

The “Pin Method” of production is adapted, with the use of completely automatic machines

MECHANISMS:

  • dipping, spinning, drying, stripping and joining the capsules.
  • The entire process takes about 45 minutes.
Proper Storage of Empty Hard Gelatin Capsules:
  • Temperature of storage should not exceed 100 degree Fahrenheit
  • Open storage under either high or low humidity should be minimized.
  • Empty gelatin capsule must contain 12 – 15 % moisture. Below 10% moisture content, the capsules become brittle and may shrink
  • Exposure to either heat or excessive moisture should be avoided, as it could cause the “distortion” of the capsule shells.
Finishing Filled Hard Gelatin Capsules
  1. Salt Polishing
  2. Pan Polishing
  3. Cloth dusting
  4. Brushing
Pan Polising
— polyurethane or cheesecloth
Cloth Dusting
— The bulk filled capsules are rubbed with a cloth (may or may not be impregnated with oil)
Brushing
— rotating soft brushes/vacuum
  Disadvantage:
  • deformation of the capsules (by scratching the surface of the shell)
  • No commercial equipment available

Special Techniques for Hard Gelatin Capsules
  1. Imprinting
    • A convenient method for purposed of product identification and control. This is best performed on empty capsules. Edible inks and used for imprinting.
  2. Sealing and/or Banding Operations

      Utilize for the following reasons:

    • provide distinctive appearance to the product
    • prevent filled capsules from unjoining
    • permit color coding
    • provide a tamper proof feature to individual capsule
  3. Locking Capsules
    • Deliberate modification is made on one or more of the normal contours of the capsules so that the body is more tightly held, in relation to the cap after closing.
  4. Special purpose Capsules
    • It refers to special capsules to which a special treatment has been given to retard the solubility.
      Example: Enteric capsules

Pharmaceutical Application of Soft Gelatin Capsules
  • As an oral dosage form for ethical or proprietary products for human or veterinary use. May be modified to impart enteric, chewable or sustained release properties.
  • As a suppository for rectal or vaginal use.
  • As a specialty package in tube form for human or veterinary single dose application of topical and ophthalmic preparations, rectal ointments, ear and nose drops.
  • In the cosmetic industry, as a specialty package for breath fresheners, perfume, bath oils, bubble baths, shampoos, suntan oils, etc.
Method of Production of Gelatin Capsules

A. PLATE PROCESS

B. ROTARY DIE PROCESS

C. RECIPROCATING DIE PROCESS

A. Plate Process

The oldest, commercial method

Steps of Plate Process:
  1. A warm sheet of gelatin (plain or colored) is placed on the bottom plate of the mold and the liquid medication is poured on it.
  2. A second sheet of gelatin is carefully laid in place, on top of the medication. The top plate of the mold is put in place.
  3. The entire mold is subjected to a press to form, fill and seal the capsules, simultaneously.
  4. The capsules are removed and washed with neutral solvent.
B. Rotary Die Process

A continuous process of production of Soft Gelatin Capsules, invented by Scherer in 1993.

  1. Ribbons of gelatin are fed between a set of vertical dies, that continually open and close, forming rows of gelatin ribbon “pockets”.
  2. The gelatin ribbon “pockets” are filled with the medication, then sealed, shaped and cut out of the film.
  3. The filled capsules are cut away from the ribbons, fall into refrigerated tanks, to prevent capsules from adhering to each other.
C. Reciprocating Die Process

Developed in 1949

Steps of Reciprocating Die Process:
  1. Liquid gelatin flows from the overhead tank, forms 2 continuous ribbons by the rotary die machine, and brought together by 2 rotating dies.
  2. Simultaneously, calibrated drug fill material is injected between ribbons.
  3. The filled gelatin pockets are sealed by the application of pressure and heat.
  4. The sealed capsules are cut-away from the continuous gelatin ribbons

MICROENCAPSULATION

— a process in which tiny particles or droplets are surrounded or coated with a continuous film of polymeric material to give more useful properties.

Importance of Microencapsulation

  • Provide means of converting liquids to solids
  • Alteration of colloidal and surface properties
  • Provide environmental protection
  • Control of release characteristics or availability of coated materials.

Microencapsulation produces

  • sustained-release or prolonged actionmedication
  • taste masked tablets
  • powders and suspensions
  • single layer tablets containing chemically incompatible materials
  • new formulation concepts for semi-solids, aerosols, suppositories and injectables.
CAPSULE STANDARD
  • Comply with official compendia
  • Uniformity of Fill Weight
  • Disintegration and dissolution tests
Uniformity of Fill Weight Test

— Simple means of estimating content of active ingredient per capsule.

  1. Weighing specific number of capsules
  2. Emptying out their contents
  3. Reweighing the shells
  4. Calculating the weight of fills