Suppositories Flashcards
what are medication sticks
dosage form for administering topical drugs
what are common soft sticks
cosmetic preparations (lip balm, deodorant) convenient to apply topical drugs
What are hard sticks made of
Crystalline powders fused or bound together with cocoa butter or petrolatum
ex: styptic pencil
what is a suppository
A solid dosage form used for rectal, vaginal, urethral administration
Consists of a dispersion of the active ingredient in an inert matrix ( a rigid or semi-rigid base)
Disadvantages of suppositories
More invasive
Sometimes absorption is variable
They may be a bit more to manufacture
advantages of suppositories
Can be used in people who can’t take oral medication
Unconscious patients
What are some applications of suppositories
Local effect: antihaemorrhoidal, contraceptive preps
Systemic effect: analgesics, antiasthmatics
where are drugs absorbed in the rectum?
Inferior/middle rectal vein to the general circulation
Miss first pass metabolism
Need to make sure that most of the drug is administered in the lower part of the rectum
Drug factors that affect drug absorption from suppositories
Degree of ionization (unionized is better)
Solubility of drug (lipophilic is better)
Particle size (smaller is better)
Partition coefficient of drugs between vehicle and rectal fluid
Vehicle factors that affect drug absorption from suppositories
Melting point and liquefaction (need them to melt at body temp so drug can be released)
Viscosity (make sure that the active ingredient mixes with the vehicle so it needs to be viscous enough to maintain homogenous mix of drug and vehicle (no sedimentation)
physiological factors that affect drug absorption
pH of rectal fluids Colonic content (better for it to be empty)
what is the rate limiting step in drug absorption from the rectum?
THICKNESS OF MUCOSAL MEMBRANE
physiochemical considerations for formulating suppositories (9)
spreadability
melting temperature (need melting for absorption)
presence of water (optimize water content: without water the fats may be hydrolyzed, can have drug excipient interactions, or bacterial contamination)
Hygroscopicity (PEG: might cause irritation because of the hygroscopic properties, add water right before administration and then administer)
Viscosity (low viscosity can cause sedimentation can add aluminum monostearate)
Brittleness (synthetic fat bases, overcome by adding plasticity imparting compounds-Tween 80, Castor oil)
Density
Volume contraction
Incompatibilities
Drugs that are good choices for suppositories
Poorly absorbed orally Unacceptable taste Irritating to the GI mucosa Drug of abuse Properties of the drug (physical appearance: liquid, pasty, solid; Bulk density; Solubility)
What are properties to consider when choosing a base
Physiochemical properties Release characteristics Inertness Stability during manufacturing Essential properties during production, storage, and use
When to use a fatty base
when the drug is highly soluble in water
when to use a water-miscible base
when the drug is highly soluble in fat
Fatty bases used in suppositories
Cocoa butter
Hydrogenated vegetable oil: adeps solidus, Witepsol
what is cocoa butter
Natural triglyceride
melts at body temp, solidifies at 25 degrees C
Has 4 polymorphic forms
Requires mold lubrication
what is hydrogenated vegetable oil
semi-synthetic
waxy solids
self-lubricating and contract in mold
NO polymorphism
what are water-soluble bases used in suppositories
glycerin based
PEGs
what is PEG
has a melt point above body temp but dissolves and mixes with rectal fluid
chemically stable, inert
no mold lubricant needed
What is an additive that improves incorporation of active ingredients
MgCO3: for glycerol into lipidic base
Fixed oils: to levigate solids
Water
what is an additive that increases hydrophilicity
Ionic surfactants (anionic, SDS, sodium-lauryl sulfate, TEA-stearate) Non-ionic surfactants (Tween, Labrafil, Cremophor)
what are some additives that improve viscosity
Al-monosterate, glyceryl monostearate
Stearyl, myristyl, cetyl alcohols
Bentonite, colloidal silica
what are some additives that modify melting points
Fatty acids, fatty alcohols, waxes
Sometimes the base may have a melting point range but addition of drug may change the melting point
Adding these brings the formulation back to a certain melt point
what is an additive that increases mechanical strength
Synthetic bases
what are additives that protect against degradation
Antimicrobial, antifungal, antioxidant
what are the general compounding steps
Mold preparation
Mold calibration
Base preparation Preparation of the active drug
Mixing and pouring
Cooling and finishing Packaging, storage, and labelling
what are the steps of fusion
Melt base Incorporate drug Pour melt into molds while stirring Allow to melt and congeal Remove suppositories from mold
Can lubricate the molds with mineral oil silicones
what is compression
No problems with sedimentation
Increased rate of production
Elimination of temperature change related problems
Disadvantage: requires finely powdered excipients
what is hand rolling
Doesn’t require special calculation
Mostly for cocoa butter
Tedious, requires experience
Not very uniform
steps of hand rolling
Triturate drug and base together in mortar
Use your hand to make a round shape with the mixture
Flatten to a rod shape and then cut from there
how do fatty based suppositories need to be stored?
Individually wrapped to prevent contact (wrapping material: plastic/aluminum foil)
Store in a cool place
how do water soluble based suppositories need to be stored
Individually wrapped
Tightly closed containers to prevent moisture absorption (water soluble bases are hygroscopic in nature)
Store in a cool place EXCEPT for PEG which can be stored at room temp
steps to insert a rectal suppository
- lubricate the tapered end of the suppository with lube or water
- Lay on one side with one leg bent and the other straight or with one leg on a chair
- seperate buttocks
- gently press the suppository into the rectum until it passes the sphincter
- close your legs or stay still for 15 minutes and avoid emptying bowels for at least one hour also avoid excessive movement for 1 hour
steps to insert a vaginal suppository
- Place suppository in applicator
- Lay on your back with your knees bent or stand with feet spread apart
- Gently insert the applicator into the vagina as far as it will go comfortably
