Lecture 18 Pharmaceutics of Suppositories Low
SUPPOSITORIES: solid medicinal dosage forms formulated SUPPOSITORY BASES:
and prepared for administration into body cavities • Solid form at room temp. 15-25oC and melts at body temp (for oil-based suppositories)
• Rectal, vaginal (pessary), urethral suppositories • Amorphous, smooth, non-irritating vehicle
• Melt at body temperature or dissolved by mucous or • Medicinally inert without side effects
body secretions locally • Types:
• Produce a local action, may have systemic absorption o Oleaginous (fatty/oily) bases (lipophilic)
and/or mechanical/physical effect ▪ Theobroma Oil (cocoa butter) & synthetic triglyceride mixtures
• Available as commercial preparations or compounded o Water soluble bases (hydrophilic)
OLEAGINOUS SUPPOSITORY BASES:
URETHRAL SUPPOSITORY: alprostadil (PGE1) micro-
suppository (Muse) COCOA BUTTER (THEOBROMA OIL): SYNTHETIC TRIGLYCERIDES:
• Erectile dysfunction treatment • Forms a solid < 30oC and melts at • Hydrogenated vegetable oils
125 – 1000 mcg (4 strengths) 30-35oC o Polypeg Suppository Base
• Stimulates adenyl cyclase, raising cAMP which leads to o Do not heat > 35o because it’s o Fattibase (TGs from palm,
lower Ca ion and resulting relaxation of smooth polymorphic = convert to palm kernel, coconut oils)
muscle increasing arterial blood flow to corpora metastable structure that o Wecobee (coconut oil) FS,
cavernosa penile erection melts at lower temp (< 25o C) M, R, and S (various melting
• Onset 5-10 mins; duration 30-60 mins • Non-irritating oil which is capable points) 33-40o
of dissolving certain drugs • Other bases:
• MP can also be altered by drugs o Dehydag
SUPPOSITORY ADMINISTRATION: pics on slides 6-8
o Lower MP: phenols (estradiol, o Hydrokote
Propofol, diethylstilbestrol, o Suppocirr
RECTAL DRUG DELIVERY: choral hydrate) o Witepsol
• Various levels of acceptability in different countries o Raise MP: additives like
and cultures (more common in Europe) beeswax and spermaceti help
• 10-25 mL can be retained reasonably well in rectum
o Relatively constant environment with
reproducible absorption (temp is WATER SOLUBLE BASES:
consistent, pH mostly consistent) • Contain glycerinated gelatin or the PEG polymers
• Avoids first pass effect by liver • Can be used to dissolve a single drug or 2 or more drugs
• May melt at temperatures higher than body temp
FACTORS AFFECTING RECTAL DRUG ABSORPTION: • May not require refrigeration
• Colonic/rectum content: better absorption when • Useful for prolonged release or delayed release of medication from suppository
rectum is empty (passive diffusion)
• Absorption via lower hemorrhoidal veins: leads POLYETHYLENE GLYCOL POLYMERS: GLYCERINATED GELATIN:
directly to inferior vena cava • Available in a wide range of • Translucent, resilient, gelatinous solids
• pH of rectal fluids: weak acids/bases = better absorbed hardness and melting points • Dissolve or disperse in mucous
• Lipid-water partition coefficient: high = better absorb • Does not melt at body temp secretions, provides prolonged release
• Degree of ionization (can be stored at room temp) of active ingredients with dissolution
• Particle size: smaller particle size is better absorbed • Can be molded or compressed of suppository
• One or more drugs can be • Keep in air tight container as it can
USES: formulated into these bases absorb moisture from the air
• When oral administration is difficult (N&V) or drug is • PEG combinations: • Preservative required if prolonged
incompatible with GIT, or parenteral involves higher o PEG 1450 (30%)/8000 storage (> 30 days)
risks or barriers (70%) = high MP • Use water or water-based lubricant
• Nausea, motion sickness, anxiety, and bacterial or o PEG 300 (60%)/PEG 8000 for administration
fungal infections (40%) = med MP
• Drugs for systemic treatment where other routes of o PEG 30 (48%)/PEG 6000
administration are limited or difficult (52%) = low MP
o Children, unconscious …
ABSORPTION ENHANCERS:
SUPPOSITORY FORMULATION: • Increase rectal absorption of active ingredients by enhancing membrane permeability
• Suppository base o Capric acid, lauric acid, sodium caprate or laurate or cholate or salicylate
• Medicinal ingredient o Sometimes unpredictable absorption increase
• Shape and size • Non-ionic surfactants can be added to oil base suppositories to increase release of
• Excipients needed for formulation lipophilic active substance
o Absorption enhancers
POURING: EXCIPIENTS:
• Pouring temperature: has to do with behavior of • Are used as fillers (less costly than bases)
suppository base upon cooling • Can be used as dispersing agents to more evenly spread & homogenize active ingredients
• Pouring from a mortar: last suppositories have more • Used to stabilize the compound
drug than the first ones • Act as a preservative
• Pouring from squeeze bottle: first suppositories have
more drugs than last ones
Lecture 18 Pharmaceutics of Suppositories Low
FORMULATION DECISIONS:
Pros Cons
CHOICE OF DOSAGE Suppository • Easy administration • Melting takes times
FORM • Mostly suspension
Enema • No melting process • Packaging more complex
• Mostly solution • Demanding administration
• Larger volume may give faster absorption
CHOICE OF BASE Fatty • Hardly any incompatibility • 2 compartments takes more time
Water • 1 compartment faster • Dissolution of suppository takes more time than
the melting of a fatty one
CHOICE OF ACTIVE Salt/free base/free • Form not soluble in base (is) often positive for • Active substance, very badly soluble in rectum
SUBSTANCE acid a faster release fluid, is hardly absorbed
• Best form in combo with type of base has to • Active substance, completely ionized, is hardly
be chosen based on literature data absorbed
CHOICE OF PARTICLE Fatty base, active • Rate of particle transport to interface • Particles maximal 180 µm, otherwise the
SIZE (for susp) substance, good determines rate of active substance release preparation will be difficult
water soluble • Larger particles have faster transport and • Particles > 240 µm not optimally spread with
therefore a faster release the base slower release
Fatty base, active • Extent of interface determines rate of release • Very small particles may irritate the rectal
substance, poorly • Small particles do better spread with the base mucosa if the solubility is a little better
water soluble • Best choice is a large volume of the dosage • Ex// ASA does, paracetamol does not
form and a small particle size
Water (soluble) base, • Small particles dissolve faster • Particles maximal 180 µm, otherwise the
active substance, • Larger volume of dosage form faster preparation will be difficult
poorly water soluble absorption
OTHER CHARACTERISTICS:
Hydroxyl value • Varying the ratio of mono-, di- , tri- glycerides yields varying hydroxyl values
• Higher hydroxyl value results in higher elasticity and higher viscosity
o Suspending substances better when molten
o Less fracturing after cooling
• Low hydroxyl values release drugs faster
Acid value • Lower acid value has less chemical reactivity = results in less irritation to mucous membranes
• Affects ionization of the drug, ionized drugs do not cross membranes and cannot exert effect
Iodine value • Is a measure describing the number of double bonds in an oil or fat
• Large number of double bonds is associated with increased tendency for oxidation (leading to deterioration and loss of effect and
may produce odors)
Peroxide value • The measure of reactive oxygen in the fat base
• Low peroxide value results in less oxidation of active substances by the base, allowing easily oxidizable drugs like chlorpromazine
to be formulated
