SUPPOSITORIES - Definition - merits - limitations - formulations - suppository bases - compounding - labeling - displacement value - evaluation

- solid or stiffened semi-solid dosage form for insertion into body cavities other than mouth Types Rectal Vaginal (pessaries) Urethral bougies Ear (ear cones) Nose bougies

Merits: Local effects Systemic effects Mechanical effects Bye pass first pass metabolism Alternative route for unconscious, elderly patients etc Unpleasant drugs Avoids gastric irritation & GI instability Prolonged drug release

Limitations: Aesthetic objection Leakage Unpredictable absorption Mucosal damage Formulation: Drug Base Other additives – surfactants, soothing agents, antioxidants, preservatives, anti-settling agents (blend of higher m.p waxes & fatty acids )

Methods of preparation: Hand rolling method (trituration) Moulding method (fusion) Cold compresion method Labeling: - For rectal use only - Store in a cool dry place or - To be refrigerated etc

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

Bases: I. Oleaginous (fatty) bases a) Natural - cocoa butter or their substitutes b) Synthetic - witepsol, massuppol II. Hydrophilic (water soluble/miscible) bases a) Natural - glycero gelatin b) Synthetic - macrogols Cocoa butter: m.p 30 – 36oc Readily liquefiable on warming and rapid setting on cooling Blandness

Limitations: Polymorphism – unstable gamma/beta forms Adhere to mould due to contractility on solidification Softening point too low for hot climates (beeswax may be added) Batch to batch variation in composition Becomes rancid on storage Immiscible in body fluids and poor water absorption Tendency to leak, immiscibility makes it not suitable for vaginal and urethral route May melt at warmer climates

Synthetic bases: - readily available - do not become rancid - chemically more inert - do not exhibit polymorphism - good water absorption and emulsification properties - lubrication can be avoided - white, smooth & odorless - may become brittle & fracture if cooled rapidly

Glycero-gelatin: - may cause irritation due to dehydration of mucosa - hygroscopic, careful storage - incompatible with many drugs - chance for microbial growth - base preparation is time consuming - sticky, can’t be used for hand rolling

Macrogols: - combination for adjusting m.p, hardness etc - may produce irritation due to hygroscopic nature - suitable for tropical climates - good solvent properties - less liable to leakage due to high viscosity - do not become rancid - physiologically inert - do not support microbial growth - give clean & attractive suppositories - form complex with some drugs & retard release

Displacement value: - the number of parts by weight of drug that displaces one part of base. Calculation of DV: Wt. of 6 CB suppository, WCB Wt. of 6 medicated(40%) suppository, WMS Wt. of drug in suppository, WD = WMS x 40/100 Wt. of CB in suppository, WB = WMS – WD Wt. of CB displaced by drug, WDCB = WCB – WB Displacement value, DV = WD /WDCB

Evaluation: - appearance - wt. variation - content uniformity - melting temp. - drug release - stability studies