Suppositories

• Suppositories


  Solid dosage forms of various weights and shapes, usually medicated, for insertion into the rectum, vagina, or urethra. After insertion, they soften, melt, disperse, or dissolve in the cavity fluids.
• Pessaries


  A type of suppository intended for vaginal use. They have various shapes, usually ovoid, with a volume and consistency suitable for insertion into the vagina.
• Bougies


  Inserted into the urethra, prostrate, bladder or nose for the treatment of different ailments or for diagnoses.
• The use of suppositories dates from the distant past, this dosage form being referred to in writings of the early Egyptians, Greeks, and Romans.
• Suppositories can be used to achieve systemic or local effects.
• Pessaries are used almost exclusively for local medication, the exception being prostaglandin pessaries that exerts a systemic effect. While rectal suppositories can be used to exact local or systemic effects.
• Common Active Pharmaceutical Ingredients for inclusion in pessaries for local action

  • Antiseptics
  • Contraceptive agents
  • Local anaesthetics
  • Various therapeutic agents to treat trichomonal, bacterial and monilial infections
• Rectal Suppositories


  The USP describes rectal suppositories for adults as tapered at one or both ends and usually weighing about 2 g each. Infant rectal suppositories usually weigh about one-half that of adult suppositories.
• Vaginal Suppositories


  The USP describes vaginal suppositories, or pessaries, as usually globular or oviform and weighing about 5 g each.
• Urethral Suppositories


  Urethral suppositories, or bougies, are not described specifically in the USP, either by weight or dimension. Traditional values, based on the use of cocoa butter as a base, are as follows for these cylindrical dosage forms: diameter: 5 mm; length: 50 mm female, 125 mm male; weight: 2 g female, 4 g male.
• Advantages of suppositories as dosage forms

  • Can exert local effect on rectal mucosa
  • Used to promote evacuation of bowel
  • Avoid any gastrointestinal irritation
  • Can be used in unconscious patients
  • Can be used for systemic absorption of drugs, in order to avoid first-pass metabolism
• Disadvantages of suppositories as dosage forms

  • May be unacceptable to certain patients
  • May be difficult to self administer by arthritic or physically compromised patients
  • Unpredictable and variable absorption in vivo
• Preparation of Suppositories


  Incorporating the medicaments into the base and the molten mass is then poured at a suitable temperature into moulds and allowed to cool until set.
• Suppository Bases (Vehicles)


  The ideal suppository base should be non-toxic and non-irritating to mucous membranes, compatible with a variety of drugs, melt or dissolve in rectal fluids, be stable on storage, and not bind or interfere with release or absorption of drug substances.
• Types of suppository bases

  • Fatty
  • Water soluble or water miscible
• Cocoa Butter


  A naturally occurring triglyceride with about 40 percent unsaturated fatty acid content. It exhibits polymorphism and requires careful temperature control during processing to achieve the desired crystal form and melting point.
• Glycerinated Gelatin


  Composed of water, the drug (10 percent w/w), glycerin (70 percent), and gelatin (20 percent). Usually used as a vehicle for vaginal suppositories.
• Other water soluble bases

  • Polyethylene glycols of 1000, 4000, or 6000 molecular weight
  • Selected nonionic surfactant materials such as polyoxyl 40 stearate and polyoxyethylene derivative of sorbitan monostearate
• Preparation techniques for suppositories

  1. Rolling (hand-shaping)

  2. Cold compression

  3. Fusion or Melt Molding
• Commercial preparation of Suppositories

  1. Automated filling of molds or preformed shells by a volumetric dosing pump that meters the melt from a jacketed kettle or mixing tank directly into the molds or shells

  2. Injection Molding using polyethylene glycols as the excipients of choice
• Calibration of Suppository moulds is important
• Emulsions


  A two-phase system prepared by combining two immiscible liquids, in which small globules of one liquid are dispersed uniformly throughout the other liquid. The liquid dispersed into small droplets is called the dispersed, internal, or discontinuous phase. The other liquid is the dispersion medium, external phase, or continuous phase.
• Emulsifier


  An emulsifying agent or surfactant that is necessary to stabilize the emulsion.
• Oil-in-water (O/W) emulsion


  Where oil is the dispersed phase and an aqueous solution is the continuous phase.

  
• Water-in-oil (W/O) emulsion


  Where water or an aqueous solution is the dispersed phase and oil or oleaginous material is the continuous phase.

  
• Multiple emulsions


  Include o/w/o and w/o/w, formed by re-emulsification of an existing emulsion to form two disperse phases.
• Advantages of emulsions


  • Improve dissolution and bioavailability of poorly water soluble drugs
  • Mask bitter or unpleasant taste or odor
  • Control absorption rate and permeation
  • Enable organ targeted delivery
  • Provide protection against oxidation or hydrolysis
  • Achieve delayed, sustained or controlled drug delivery
• Advantages of o/w emulsion over w/o for dermatological use: they rub into the skin more readily, are easily removed by washing, less likely to soil clothes, cause a cooling effect, and readily mix with tissue exudates.
• Self-emulsifying drug delivery systems (SEDDS)


  Emulsion concentrates composed of drug(s), oil(s), surfactant(s) and co-solvents.
• Nanoemulsions


  A type of emulsion.
• Formulation of emulsions


  Select the right excipients and emulsion type, choose and optimize the processing technique and conditions, consider potential toxicity, incompatibilities, and cost.
• On/w emulsions


  • Rub into skin more readily
  • Easily removed by washing
  • Less likely to soil clothes
• On/w emulsions


  • Evaporation of aqueous phase causes cooling effect
  • Interference with heat loss by oil phase is reduced as it is discontinuous
• On/w emulsions


  • Readily mix with tissue exudates in wounds, causing rapid healing unlike w/o types
• Self-emulsifying drug delivery systems (SEDDS)

  Emulsion concentrates composed of drug(s), oil(s), surfactant(s) and co-solvents
• Formulation of emulsions


  1. Select right excipients (oil, emulsifier, etc.) and emulsion type

  2. Choose and optimize processing technique and conditions
• Considerations in formulation


  • Potential toxicity of excipients
  • Possible chemical and physical incompatibilities
  • Cost of excipients
• Oils used in Pharmaceutical Emulsions

  • For external preparations: liquid paraffin, soft paraffin, hard paraffin, turpentine oil, benzyl-benzoate, silicone oils
  • For oral emulsions: Castor oil, liquid paraffin, fish liver oils, arachis oil
  • For parenteral emulsions: Vegetable oils like purified and modified soya bean oil, sunflower oil, coconut oil, cottonseed oil
• Choice of emulsifying agents

  • Based on type of emulsion, toxicity profile, final clinical use, targeted droplet size, surface charge, properties of dispersed phase, potential cost and availability

  
• Classification of emulsifying agents

  • Synthetic and semi-synthetic
  • Natural materials and their derivatives