SUPPOSITORIESSUPPOSITORIES- Definition- Definition

- merits- merits

- limitations- limitations

- formulations- formulations

- suppository bases- suppository bases

- compounding- compounding

- labeling- labeling

- displacement value- displacement value

- evaluation- evaluation

- solid or stiffened semi-solid dosage form for - solid or stiffened semi-solid dosage form for insertion into body cavities other than mouthinsertion into body cavities other than mouth

TypesTypes

1.1. RectalRectal

2.2. Vaginal (pessaries)Vaginal (pessaries)

3.3. Urethral bougiesUrethral bougies

4.4. Ear (ear cones)Ear (ear cones)

5.5. Nose bougiesNose bougies

Merits:Merits: Local effectsLocal effects Systemic effectsSystemic effects Mechanical effectsMechanical effects Bye pass first pass metabolismBye pass first pass metabolism Alternative route for unconscious, elderly patients Alternative route for unconscious, elderly patients

etcetc Unpleasant drugsUnpleasant drugs Avoids gastric irritation & GI instabilityAvoids gastric irritation & GI instability Prolonged drug releaseProlonged drug release

Limitations:Limitations: Aesthetic objectionAesthetic objection LeakageLeakage Unpredictable absorptionUnpredictable absorption Mucosal damageMucosal damage

Formulation:Formulation: DrugDrug BaseBase Other additives – surfactants, soothing agents, Other additives – surfactants, soothing agents,

antioxidants, preservatives, anti-settling agents antioxidants, preservatives, anti-settling agents (blend of higher m.p waxes & fatty acids ) (blend of higher m.p waxes & fatty acids )

Methods of preparation:Methods of preparation:

1.1. Hand rolling method (trituration)Hand rolling method (trituration)

2.2. Moulding method (fusion)Moulding method (fusion)

3.3. Cold compresion methodCold compresion method

Labeling:Labeling:

- For rectal use only- For rectal use only

- Store in a cool dry place or- Store in a cool dry place or

- To be refrigerated etc- To be refrigerated etc

Ideal properties of a suppository baseIdeal properties of a suppository base::- Easily melt and dissolve or disperseEasily melt and dissolve or disperse- Release medicament readilyRelease medicament readily- Retain shape while handlingRetain shape while handling- Non-toxic & non-irritantNon-toxic & non-irritant- Stable & compatibleStable & compatible- Moldable, non adheringMoldable, non adhering

BasesBases::I. Oleaginous (fatty) bases I. Oleaginous (fatty) bases a) Natural - cocoa butter or their substitutesa) Natural - cocoa butter or their substitutes b) Synthetic - witepsol, massuppolb) Synthetic - witepsol, massuppolII. Hydrophilic (water soluble/miscible) bases II. Hydrophilic (water soluble/miscible) bases

a) Natural - glycero gelatina) Natural - glycero gelatinb) Synthetic - macrogolsb) Synthetic - macrogols

Cocoa butterCocoa butter::- m.p 30 – 36m.p 30 – 36oocc- Readily liquefiable on warming and rapid setting Readily liquefiable on warming and rapid setting

on coolingon cooling- BlandnessBlandness

Limitations:Limitations:- Polymorphism – unstable gamma/beta formsPolymorphism – unstable gamma/beta forms- Adhere to mould due to contractility on Adhere to mould due to contractility on

solidificationsolidification- Softening point too low for hot climates (beeswax Softening point too low for hot climates (beeswax

may be added)may be added)- Batch to batch variation in compositionBatch to batch variation in composition- Becomes rancid on storageBecomes rancid on storage- Immiscible in body fluids and poor water Immiscible in body fluids and poor water

absorptionabsorption- Tendency to leak, immiscibility makes it not Tendency to leak, immiscibility makes it not

suitable for vaginal and urethral routesuitable for vaginal and urethral route- May melt at warmer climatesMay melt at warmer climates

Synthetic basesSynthetic bases::

- readily available- readily available

- do not become rancid- do not become rancid

- chemically more inert- chemically more inert

- do not exhibit polymorphism- do not exhibit polymorphism

- good water absorption and emulsification - good water absorption and emulsification propertiesproperties

- lubrication can be avoided- lubrication can be avoided

- white, smooth & odorless- white, smooth & odorless

- may become brittle & fracture if cooled rapidly- may become brittle & fracture if cooled rapidly

Glycero-gelatin:Glycero-gelatin:

- may cause irritation due to dehydration of - may cause irritation due to dehydration of mucosamucosa

- hygroscopic, careful storage- hygroscopic, careful storage

- incompatible with many drugs- incompatible with many drugs

- chance for microbial growth- chance for microbial growth

- base preparation is time consuming- base preparation is time consuming

- sticky, can’t be used for hand rolling - sticky, can’t be used for hand rolling

MacrogolsMacrogols::

- combination for adjusting m.p, hardness etc- combination for adjusting m.p, hardness etc

- may produce irritation due to hygroscopic - may produce irritation due to hygroscopic naturenature

- suitable for tropical climates- suitable for tropical climates

- good solvent properties- good solvent properties

- less liable to leakage due to high viscosity- less liable to leakage due to high viscosity

- do not become rancid- do not become rancid

- physiologically inert- physiologically inert

- do not support microbial growth- do not support microbial growth

- give clean & attractive suppositories- give clean & attractive suppositories

- form complex with some drugs & retard release- form complex with some drugs & retard release

Displacement valueDisplacement value::

- the number of parts by weight of drug that - the number of parts by weight of drug that displaces one part of base.displaces one part of base.

Calculation of DV:Calculation of DV:

1.1. Wt. of 6 CB suppository, WWt. of 6 CB suppository, WCBCB

2.2. Wt. of 6 medicated(40%) suppository, WWt. of 6 medicated(40%) suppository, WMSMS

3.3. Wt. of drug in suppository, WWt. of drug in suppository, WD D = W= WMS MS x 40/100x 40/100

4.4. Wt. of CB in suppository, WWt. of CB in suppository, WB B = W= WMS MS – W– WDD

5.5. Wt. of CB displaced by drug, WWt. of CB displaced by drug, WDCB DCB = W= WCB CB – W– WBB

6.6. Displacement value, DV = WDisplacement value, DV = WD D /W/WDCBDCB

EvaluationEvaluation::

- appearance- appearance

- wt. variation- wt. variation

- content uniformity- content uniformity

- melting temp.- melting temp.

- drug release- drug release

- stability studies - stability studies