capsules

• Encapsulation

  Techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them to be taken orally or used as suppositories
• Types of capsules


  • Hard-shelled capsules
  • Soft-shelled capsules
• Hard-shelled capsules

  • Contain dry, powdered ingredients or miniature pellets
  • Made in two-halves: a smaller-diameter "body" that is filled and then sealed using a larger-diameter "cap"
• Soft-shelled capsules


  • Primarily used for oils and for active ingredients that are dissolved or suspended in oil
  • Made from aqueous solutions of gelling agents, such as animal protein (mainly gelatin) or plant polysaccharides or their derivatives
• Other ingredients can be added to the gelling agent solution including plasticizers, coloring agents, preservatives, disintegrates, lubricants and surface treatment
• Hard gelatin capsules


  Rigid two-piece capsules made from gelatin, water and colorants
• Hard gelatin capsules

  • Produced as empty shells consisting of a cap and body, which during the manufacture of the finished product are separated, filled with the formulation and then rejoined
  • Generally considered to be more forgiving than tablets, from a formulator's perspective
• Hard gelatin capsules are filled with solid formulations such as powder mixes and granulations, but increasingly, multi particulate formulations, liquid and semi-solid fills are being developed
• Disadvantages of hard gelatin capsules compared to tablets

  • Filling speeds of capsule machines are lower than the speeds of the fastest tablet presses
  • Cost of the capsule shells makes them a more expensive dosage form
  • Certain materials are unsuitable for inclusion in capsule shells due to incompatibility with gelatin or because of their affinity for water
  • Capsules are often larger than corresponding tablets due to the reduced compression of the powder and incomplete filling of the shells
  • Capsules are more prone to sticking in the oesophagus than tablets following swallowing
• Gelatin

  A heterogeneous product prepared by the hydrolysis of collagen, the principal constituent of connective tissue
• Properties of gelatin

  • Good film former, producing a strong flexible film
  • Readily soluble in water and in GI fluids at body temperature, so will not retard the release of drugs
  • Changes state at low temperatures enabling a homogeneous film to be formed at ambient temperature
• Manufacture of empty capsule shells

  1. Dipping moulds into a gelatin solution

  2. Drying the gelatin to form a film

  3. Removing the dried film from the mould

  4. Trimming the film to the right size
• Capsule shells

  • Contain 13–15 percent water, a level that is important for optimum performance on capsule filling machines
  • Dimensions change with variations in water content, typically increasing by 0.5 percent for every 1 percent increase in moisture content
  • Must be stored and filled in areas where the relative humidity is controlled between 30–50 percent
  • Fill materials must be chemically compatible with gelatin
• Screw method for capsule filling

  1. Capsule body in its holder passes beneath the powder hopper on a turntable

  2. Powder is fed into the capsule body by a revolving archimedian screw

  3. Auger rotates at a constant rate so the fill weight is related to the duration of filling that is related to the speed of rotation of the turntable
• Piston tamp method for capsule filling

  1. Powder passes over a dosing plate containing cavities slightly smaller than the internal diameter of the capsule

  2. Powder falls into the holes by gravity and is then tamped by a pin to form a soft plug

  3. Procedure is repeated several times until the cavity is full

  4. Excess powder is removed from above the cavity by a deflector plate

  5. Cavity is then positioned over the capsule body and the plug ejected
• Soft gelatin capsules

  Drug is presented in a liquid encapsulated in a solid, combining advantages of liquid dosage forms with the unit dosage convenience of solid forms
• Manufacture of soft gelatin capsules

  1. Shell ingredients are gelatin, glycerol, and potentially other ingredients

  2. Gelatin-glycerol mix is dissolved in water, then heated and pumped onto two cooling drums to form two gelatin ribbons

  3. Liquid fill is pumped between the gelatin ribbons as they pass between the two die rolls of the filling machine, forcing the gelatin to adopt the shape of the die

  4. Two ribbons are sealed together by heat and pressure and the capsules are cut from the ribbon

  5. Capsules then pass through a tumble dryer to remove the bulk of the water and conditioned at 20 percent relative humidity
• Soft gelatin capsule formulations

  • More expensive dosage form than either tablets or capsules
  • Offer improved content uniformity, safety, improved stability and improved bioavailability
• Topical drug delivery

  • Offers advantages including reduced blood level fluctuation, obviating the first pass effect, and protection from gastrointestinal pH
  • Skin is a poor medium to deliver drugs, as it is designed to prevent the entry of chemicals
• Factors affecting transdermal drug delivery

  • Molecular weight and volume, aqueous solubility, melting point, and log P
  • For weakly acidic or basic drugs, the skin pH will play a strong role
  • Drugs that form zwitter ions can be made more penetrable by using appropriate salt forms
  • Formulation additives strongly impact on transdermal delivery