Suppositories

Question 1

what are medication sticks

Answer 1

dosage form for administering topical drugs

Question 2

what are common soft sticks

Answer 2

cosmetic preparations (lip balm, deodorant) 
convenient to apply topical drugs

Question 3

What are hard sticks made of

Answer 3

Crystalline powders fused or bound together with cocoa butter or petrolatum
ex: styptic pencil

Question 4

what is a suppository

Answer 4

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)

Question 5

Disadvantages of suppositories

Answer 5

More invasive
Sometimes absorption is variable
They may be a bit more to manufacture

Question 6

advantages of suppositories

Answer 6

Can be used in people who can’t take oral medication

Unconscious patients

Question 7

What are some applications of suppositories

Answer 7

Local effect: antihaemorrhoidal, contraceptive preps

Systemic effect: analgesics, antiasthmatics

Question 8

where are drugs absorbed in the rectum?

Answer 8

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

Question 9

Drug factors that affect drug absorption from suppositories

Answer 9

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

Question 10

Vehicle factors that affect drug absorption from suppositories

Answer 10

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)

Question 11

physiological factors that affect drug absorption

Answer 11

pH of rectal fluids 
Colonic content (better for it to be empty)

Question 12

what is the rate limiting step in drug absorption from the rectum?

Answer 12

THICKNESS OF MUCOSAL MEMBRANE

Question 13

physiochemical considerations for formulating suppositories (9)

Answer 13

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

Question 14

Drugs that are good choices for suppositories

Answer 14

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)

Question 15

What are properties to consider when choosing a base

Answer 15

Physiochemical properties 
Release characteristics 
Inertness 
Stability during manufacturing 
Essential properties during production, storage, and use

Question 16

When to use a fatty base

Answer 16

when the drug is highly soluble in water

Question 17

when to use a water-miscible base

Answer 17

when the drug is highly soluble in fat

Question 18

Fatty bases used in suppositories

Answer 18

Cocoa butter

Hydrogenated vegetable oil: adeps solidus, Witepsol

Question 19

what is cocoa butter

Answer 19

Natural triglyceride
melts at body temp, solidifies at 25 degrees C
Has 4 polymorphic forms
Requires mold lubrication

Question 20

what is hydrogenated vegetable oil

Answer 20

semi-synthetic
waxy solids
self-lubricating and contract in mold
NO polymorphism

Question 21

what are water-soluble bases used in suppositories

Answer 21

glycerin based

PEGs

Question 22

what is PEG

Answer 22

has a melt point above body temp but dissolves and mixes with rectal fluid
chemically stable, inert
no mold lubricant needed

Question 23

What is an additive that improves incorporation of active ingredients

Answer 23

MgCO3: for glycerol into lipidic base
Fixed oils: to levigate solids
Water

Question 24

what is an additive that increases hydrophilicity

Answer 24

Ionic surfactants (anionic, SDS, sodium-lauryl sulfate, TEA-stearate) 
Non-ionic surfactants (Tween, Labrafil, Cremophor)

Question 25

what are some additives that improve viscosity

Answer 25

Al-monosterate, glyceryl monostearate Stearyl, myristyl, cetyl alcohols Bentonite, colloidal silica

Question 26

what are some additives that modify melting points

Answer 26

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

Question 27

what is an additive that increases mechanical strength

Answer 27

Synthetic bases

Question 28

what are additives that protect against degradation

Answer 28

Antimicrobial, antifungal, antioxidant

Question 29

what are the general compounding steps

Answer 29

Mold preparation Mold calibration Base preparation Preparation of the active drug Mixing and pouring Cooling and finishing Packaging, storage, and labelling

Question 30

what are the steps of fusion

Answer 30

``` 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

Question 31

what is compression

Answer 31

No problems with sedimentation Increased rate of production Elimination of temperature change related problems Disadvantage: requires finely powdered excipients

Question 32

what is hand rolling

Answer 32

Doesn’t require special calculation Mostly for cocoa butter Tedious, requires experience Not very uniform

Question 33

steps of hand rolling

Answer 33

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

Question 34

how do fatty based suppositories need to be stored?

Answer 34

Individually wrapped to prevent contact (wrapping material: plastic/aluminum foil) Store in a cool place

Question 35

how do water soluble based suppositories need to be stored

Answer 35

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

Question 36

steps to insert a rectal suppository

Answer 36

1. lubricate the tapered end of the suppository with lube or water 2. Lay on one side with one leg bent and the other straight or with one leg on a chair 3. seperate buttocks 4. gently press the suppository into the rectum until it passes the sphincter 5. 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

Question 37

steps to insert a vaginal suppository

Answer 37

1. Place suppository in applicator 2. Lay on your back with your knees bent or stand with feet spread apart 3. Gently insert the applicator into the vagina as far as it will go comfortably