Suppositories

• Urethral suppositories are inserted into the urethra and are used for local effects.
• Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects.
• • Suppositories are commonly used rectally and vaginally (known as pessary) and occasionally urethrally (known as bougie). They have various shapes and weights. • Shape and size designed for easy insertion into intended orifice • and once inserted, it must be retained for the appropriate period
• Local action

  • Rectal suppositories intended for localized action are most frequently used to relieve constipation or pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions

  • A popular laxative, glycerin suppositories promote laxation by the local irritation of the mucous membranes
• Vaginal suppositories or inserts intended for localized effects are employed mainly as contraceptives, antiseptics in feminine hygiene, and as specific agents to combat against invading pathogen
• Most commonly, the drugs used are nonoxynol-9 for contraception, and trichomonacides to combat vaginitis caused by Trichomonas vaginalis, Candida (Monilia) albicans, and other microorganisms
• Systemic action

  •For systemic effects, the mucous membranes of the rectum and vagina may permit the absorption of various soluble drugs • Although the rectum is used as the site for the systemic absorption of drugs, the vagina is not commonly used for systemic absorption of drug (even though it can be quite extensive and can avoid first pass metabolism
• Advantages over oral therapy of the rectal route of administration for achieving systemic effects include the ability for drugs to be destroyed or inactivated by the pH, enzymatic activity of the stomach or intestines without being exposed to these destructive environments.
• Drugs irritating to the stomach may be given without causing such irritation through the rectal route of administration.
• Drugs destroyed by portal circulation may bypass the liver after rectal absorption, avoiding first-pass metabolism, but this may not be total avoidance depending on the position of the suppository in the rectum.
• The rectal route of administration is convenient for the administration of drugs to adult or pediatric patients who may be unable or unwilling to swallow medication.
• The rectal route of administration is an effective route in the treatment of patients with vomiting episodes.
• Disadvantages of suppositories

  May be unacceptable to certain patients/cultures

  b) May be difficult to self-administer by arthritic or physically compromised patients

  c) Unpredictable and variable absorption in vivo

  d) Upward movement of suppository (larger distance from anus) can increase first pass metabolism
• Disadvantages

  The rectum’s main blood supply is delivered by the rectal artery and is drained by the superior, middle and inferior hemorrhoidal veins

  • Note: Dilation of these veins equal to internal or external hemorrhoids

  •The chance of drugs going into the liver (first pass metabolism) is increased as the absorption site distance from the anus increases
• Properties of an Ideal Suppository Base:

  • 1. Melts at body temperature 37°C, or dissolve in rectal fluid

  • 2. Completely non toxic, and non irritating to sensitive and inflamed tissues

  • 3. Compatible with a broad variety of drugs

  • 4. No metastable forms

  • 5. Shrinks sufficiently on cooling to be released form the mould without the need for mould lubricants
• • 6. Non-sensitizing

  •7. Has a melting and emulsifying property

  •8. Water number is high (a high percentage of water can be incorporated in it)

  •9. Stable on storage, does not change odour, colour, and drug release pattern / characteristics

  •10. Can be manufactured by moulding either by hand, compression, or machine

  •11. The interval between melting point and solidification point is small
• Three methods:• 1. Fusion Moulding• 2. Compression Moulding• 3. Hand Rolling and Shaping
• Fusion Moulding•

  Commonly used on a small and large scale

  Output of typical rotary machine ranges from 3500 to 6000 suppositories an hour.

  Steps:

  Melting the base•

  Incorporating required medicaments•

  Pouring melts into moulds•

  Allowing melt to cool and congeal

  Removal from moulds
• Bases used in Fusion Moulding•

  Cocoa butter / Theobroma oil

  • Hard solid below 25°C

  • Melts at 31 to 34°C

  •Glycerinated gelatin

  •Polyethylene glycol

  • Do not melt at body temperature

  • Dissolve
• Lubrication of mould

  •Before the melt is poured

  •Required for clean and easy removal of suppositories

  •Mineral oil is applied through :

  •brushing or

  •spraying
• Lubrication (II)

  •Cocoa butter and polyethylene glycol bases seldom requirelubrication as they contract on cooling within the mould• Separate from the inner surfaces

  • Allow easy removal

  •Usually necessary with glycerinated gelatine
• Pouring the melt• Materials are poured continuously into moulds• To prevent layering leading to easy breakage
• Overfilling

  • To ensure complete filling

  • Prevents formation of recessed dips

  • Excess material form continuous ribbons along the top of the moulds

  • Excess material can be scraped off after solidification
• Compression• Fixed quantity of formulation• Forced into special compression mould• Quantity based on capacity of moulds
• Suited for making suppositories that contain:

  • Heat labile medicinal substances

  • Much substances that are insoluble in base

  • No likelihood of insoluble materials settling during manufacture
• Tests (Quality Control - Pharmacopoeial)• Uniformity of content• Uniformity of mass• Dissolution• Disintegration
• When the Density Factor is Not Known – How to make suppositories containing API Double Casting Technique

  
  

  • The total quantity of API is mixed with an amount of base, which is inadequate to fill the number of cavities

  • The mixture is poured into the mould, partially filling each cavity

  • The remaining portion of the cavities are over-filled with the melted blank base (to be trimmed when cooled – shrinkage of suppositories must be taken into account)
• When the Density Factor is Not Known – How to make suppositories containing API

  
  

  • The cooled suppositories are then removed,remelted, mixed evenly, and recast to evenlydistribute the active ingredient

  
  

  • Note:• A portion of the formula will be lost during this process, so you should always prepare for 2 extra suppositories to ensure that you have enough mixture for the desired number of suppositories