Medical Sticks & Suppositories Flashcards
What are medical sticks?
dosage form for administering topical drugs
commonly accepted as cosmetic formulations
What are some pharmaceutical applications for medical sticks?
lip balm
pain relief roll on sticks (Hot & Cold)
specialty compounds
What are soft sticks?
cosmetic preparations
convenient to apply topical drugs
ex: lip balm
What are hard sticks?
crystalline powders fused by heat or held together with binders such as cocoa butter or petrolatum
-moisture is needed to ‘activate’
Are hard sticks used in pharmaceutical applications?
not anymore
-unless as specialty compounds
Describe examples of stick bases.
fatty bases:
-cocoa butter
-vegetable oils (rancidity), mineral oil
-hydrogenated vegetable oil (Witepsol)
-waxes
water-soluble bases:
-sodium stearate/glycerol PEGs
How are medical sticks prepared?
molding
Are suppositories a widely used dosage form?
neglected dosage form
1% of drugs are manufactured as suppositories
general rejection of rectal delivery systems
What is a suppository?
a solid dosage form used for rectal, vaginal, urethral administration
What do suppositories consist of?
a dispersion of the active ingredient in an inert matrix (a rigid or semi-rigid base)
What are advantages of suppositories?
less invasive than injectables
limit first pass hepatic metabolism
limit drug interactions when given with other therapies
can be used for both local and systemic effects
accommodates patients who have difficulty swallowing pills
accommodates administration in unconscious patients or infants
increased bioavailability of drugs
What are the limitations of suppositories?
not for long-term treatment
user discomfort
special storage conditions like low temp
difficult self-administration (some populations)
Describe the rectal environment.
relatively constant environment and static in comparison to parts of the GIT
average fluid volume is 1-3ml
neutral pH of 7-8, minimal buffering
normal bacterial flora (insignificant metabolism)
small surface area for absorption compared to small intestine (although, high vasculature)
Describe rectal absorption of drugs.
through the inferior/middle rectal vein that drains into the inferior vena cava and therefore directly into systemic circulation
-superior rectal vein drains into portal vein which passes through liver prior to circulation
What are the the factors that may contribute to the absorption of drugs via rectal route?
physiological factors
formulation factors
What are the formulation factors which impact rectal absorption?
- partition coefficient
- physical state of the drug in theb. formulation
- solubility, degree of ionization, particle size
a. solubility in rectal fluid determines maximum concentration available for absorption
b. pKa (unionized being lipophilic and favour transcellular route)
c. lower particle size=favours dissolution
What are the physiological factors which impact rectal absorption?
anatomical size differences between rectum of adults and children
site of drug delivery in rectum
changes in rectal pH based on age or disease (impact absorption, irritation)
presence of stool affects viscosity of rectal contents
frequency of bowel movements (affects contact time)
pathological changes in tissue integrity changes thickness of mucosal membrane
Describe the size and shape of rectal suppositories.
32mm long (1.5 inches)
- ~2g for adults
- ~1g for children
shape: bullet or torpedo
Describe the size and shape of vaginal suppositories.
~5g (may vary widely)
shape: globular, oviform, cone-shaped
Describe the size and shape of urethral suppositories.
male: 140mm x 3-6mm
~4g
shape: slender, pencil-shaped
What factors make a drug of choice for a suppository?
poor oral absorption
taste unacceptable
irritable to GI mucosa
drug of abuse
acid labile drug
drugs prone to enzymatic degradation
What should the vehicle for a suppository be capable of doing?
melt
soften
dissolve at body temperature
promote drug release
stay stable during manufacturing and storage
INERT
esthetically acceptable
What are examples of suppository bases?
fatty bases:
-cocoa butter
-hydrogenated vegetable oil (Witepsol)
-hydrogenated palm oil
water-soluble bases:
-glycerine based suppositories
-PEGs
Describe the choice of base depending on lipid solubility and water solubility of a drug.
low lipid solubility, high water solubility
=fatty base
high lipid solubility, low water solubility
=water-miscible base
you want the drug to be released from vehicle
Describe cocoa butter as a fatty base.
natural triglyceride
mp 31-35 C (low)
solidification point 25 C (important for transport, packaging, storage)
four polymorphic forms (major limitation)
-B=stable form (34.5 C)
What is a compounding tip for cocoa butter?
requires lubrication of the mold (sticky character)
Describe hydrogenated vegetable oils as fatty bases.
semi-synthetic (resistant to oxidation or hydrolysis)
waxy solids
no polymorphism
more flexibility and less brittle character
lower viscosity (sedimentation risk=lack of uniformity)
What is a compounding tip for hydrogenated vegetable oils?
they are self-lubricating but contract in mold
What are examples of hydrogenated vegetable oils?
Witepsol
Suppocire
Describe glycerol-gelatin base as a water-soluble base.
mixture of glycerol and water stiffened with gelatin
very rare to use (not inert, have laxative effect)
dissolution varies with age of suppository
hygroscopic (storage conditions are critical)
Describe PEG as a water-soluble base.
used as combination of PEGs with different MPs and dissolution rates
slow drug release
some polymers MPs>body temp (sustained drug action)
chemically stable but not physically stable
What are the limitations of PEG as a water-soluble base?
hygroscopic (storage critical)
several incompatibilities with APIs
may become brittle on storage
What is a compounding tip for PEG?
prepared by both molding and compression, no lubrication needed
What are the additives for suppositories?
to improve incorporation of API:
-fixed oils (levigates solids)
-water
increase hydrophilicity and dissolution:
-ionic surfactants (anionic, SDS, SLS)
-non-ionic surfactants (Tween)
to improve viscosity:
-Al-monostearate, glyceryl monostearate
-stearyl, myristyl, cetyl alcohols
-bentonite, colloidal silica
to modify melting point
-fatty acids, fatty alcohols, waxes
to protect against degradation
-antimicrobial, antifungal, antioxidant
Why is the rectal route preferential for increased bioavailability?
the walls of the rectum are highly vascularized and absorb many medications quickly and effectively
medications delivered to the distal one-third of the rectum at least partially avoid first pass
As a pharmacist, when would you consider rectal route?
pediatric patients
patients experiencing dysphagia
infractable N/V
refusing oral meds or spitting out
patients with GIT obstruction
patients with esophageal stricture or malignancy
loss of consciousness/palliative care
decreased mental status
As a pharmacist, when would you avoid rectal route?
neonatal patients
patients who have conditions associated with neutropenia (infection risk)
thrombocytopenia (bleed risk)
chronic constipation
increased GI motility (diarrhea)
when placement will cause pain (fissure, hemorrhoids)
What are the general suppository compounding steps?
mold preparation
mold calibration
base preparation
incorporation of active drug (displacement factor)
mixing and pouring
cooling and finishing
packaging, storage and labeling
What is the displacement factor?
measure of the amount of active substance (in grams) that displaces 1g of suppository base
-it is available in literature for common drugs
-affects final suppository weight and dosing uniformity of the formulation especially for drugs which exhibit high displacement factors
What are the three preparation methods for suppositories?
molding (fusion)
compression
hand rolling
most suppository bases are suitable for molding
Describe cold compression.
same machine as for tablets
no problems with sedimentation
increased rate of production
elimination of temperature change related problems
suitable for thermolabile & insoluble drugs because heating of the base with medicament is not required
mixture of base and drug, is forced into a mold under pressure, using a wheel-operated press into open molds
What is the disadvantage of cold compression?
requires finely powdered excipients
not used for extemporaneous compounding
Describe hand rolling.
does not require special calculation
mostly for cocoa butter
tedious, requires experience
not very uniform
Describe packaging and storage of suppositories.
most suppositories are individually wrapped
fatty bases: store in a cool place 2-8C
-strict temperature control
water-washable and soluble bases
-tightly closed containers to prevent moisture absorption (hygroscopic nature)
-PEG suppositories (stored at room temp)
What are the problems with suppositories?
splitting, cracking, pitting
sticking to mold
thickening prior to pouring
poor product homogeneity
product insufficiently solid
surface anomalies
Describe the cause of splitting, cracking, and pitting and the solution.
cause:
-excipient contracts strongly
-large gap time between pouring and cooling–>temp fluctuations
solution:
-use an excipient which crystallizes slower
-maintain optimum control of steps pouring and cooling–>minimize temp fluctuations
Describe the cause of sticking to mold and the solution.
cause:
-faulty molds (gaps between molds upon closure)
-premature removal from mold
-insufficient cooling
-insufficient lubrication
solution:
-appropriate equipment
-prolong molding period/cooling period
-use an excipient which crystallized more rapidly
-reduce cooling temperature
-sufficient lubrication
Describe the cause of thickening prior to pouring and the solution.
cause:
-high proportion of finely powdered active ingredients
-high viscosity base mixtures
solution:
-PEG: select the mixture of right PEGs
-adjust the concentration of the API in the dosage form
Describe the cause of poor product homogeneity and the solution.
cause:
-displacement factor not taken into account
-cooling too slow or too weak leading to drug sedimentation
solution:
-calculation should be carefully performed
-increase viscosity of the base
Describe the cause of product insufficiently solid and the solution.
cause:
-inclusion of air
solution:
-check the stirring level and limit the formation of air bubbles
Describe the cause of surface anomalies and the solution.
cause:
-high mp–>excipient melting at more than 60C–>longer residence in the molds–>shape abnormalities
-excipient/active ratio
solution:
-ensure mold is appropriately sealed
-use excipients to stabilize the system like surfactants
What are some counseling points regarding suppositories?
follow package inserts for instructions
for lubrication, use a water-soluble lubricant
insert the medication about a fingers length into rectum and place against rectal wall
close your legs and sit (or lay) still for about 15 mins
avoid emptying bowels for at least one hour
avoid excessive moment or exercise for at least one hour
vaginal in many cases and urethral (always) suppositories comes with an applicator
