Suppositories and inserts Flashcards
Suppositories
are solid dosage forms intended for insertion into body orifices, i.e.,
rectum, where they melt, soften or dissolve and exert local or systemic effects
Suppositories have various
shapes and weights; the shape and size must be such that it can easily be inserted into the intended orifice without causing undue distension, and once inserted, it must be retained for the appropriate period of time
Rectal suppositories are inserted
with the fingers
Inserts
are solid dosage forms that are inserted into a naturally occurring
(nonsurgical) body cavity other than the mouth or rectum, i.e., vagina and urethra
Certain vaginal inserts (and tablets) may be inserted
high in the tract with the aid of an appliance
Rectal suppositories characteristics
Usually about 32 mm (1.5 in.) long
- are cylindrical
- and have one or both ends tapered
- Some shaped like a bullet, torpedo or the little finger
Depending on the density of the base and the medicaments in the suppository, their
weights may vary
Adult rectal suppositories weigh approximately 2 g when cocoa butter (theobroma oil) is
employed as the base
– Ones used for infants and children are about half the weight and size and assume a more
pencil-like shape ( 1g)
Vaginal inserts
Also called vaginal suppositories and pessaries
- can be tablets
Vaginal inserts characteristics
Usually globular, oviform or coned-shaped and weigh about 5 g when cocoa butter is the base
Urethral inserts
Also called urethral suppositories and bougies
Urethral inserts characteristics
Slender, pencil-shaped and intended for insertion into the male or female urethra
- For males, may be 3 to 6 mm in diameter and approximately 140 mm long, although
this may vary
• When cocoa butter is employed as the base, these weigh approximately 4 g
• For females, are about half the length and weight of the male verversions, being about 70 mm long and weighing about 2 g, when made of cocoa butter
Urethral inserts are used for
the treatment of local infections and erectile dysfunction
Local and systemic action of suppositories and insert
Once inserted, the suppository base melts, softens or dissolves, distributing its
medicaments to the tissues of the region
Rectal suppositories intended for local action are most frequently used to
relieve constipation or the pain, irritation, itching and inflammation associated with
hemorrhoids or other anorectal conditions
Vaginal inserts intended for local effects are employed mainly as
contraceptives, antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen
Mucous membranes of the rectum and vagina permit
absorption of many soluble
drugs
– Rectal used frequently, the vagina not as frequently for systemic absorption
Why might it not be practical for oral administration of a drug
in some circumstances during nausea and vomiting or convulsions, in uncooperative patients and before surgery)
The rate and extent of rectal drug absorption are
often lower than with oral
absorption, possibly an inherent factor owing to the relatively small surface area available for drug uptake
Some advantages of rectal
administration
- Drugs avoid, at least partially, the first-pass effect
- Drugs destroyed or inactivated by the pH or enzymatic activity of the stomach or
intestines need not be exposed to these destructive environments - Larger doses can be administered, compared to oral administration
- Drugs irritating to the stomach may be given without causing such irritation
- No taste limitations
- Convenient for administration of drugs to patients who are unable or unwilling to
swallow medication, i.e., infants - An effective route in the treatment of patients with vomiting
- Achievement of a rapid drug effect systemically, as an alternate to injection
Some disadvantages of rectal administration
- Not preferred by patients
- Rectal absorption can be erratic
- Can be expelled after insertion
- The absorbing surface area of the rectum is much smaller than that of the small intestine
- The fluid content of the rectum is much less than that of the small intestine, which may affect dissolution
- Local irritation – Long term medication with rectal ergotamine and acetylsalicylic acid, for example, may result in rectal ulceration, and irritation after a single
administration of several drugs and formulations has been described
Factors that affect rectal absorption of drug
- Physiologic factors
2. Physicochemical factors of the drug and the base:
Physiologic factors
- Colonic content
- Circulation route
- Essentially neutral pH and lack of buffering capacity of the rectal fluid
Physicochemical factors of the drug and the base:
- Lipid-water solubility
- Particle size
- Nature of the base
Colonic content –
Greater absorption when rectum is empty
Circulation route
Drugs absorbed rectally bypass the portal circulation during their first pass
into general circulation, enabling drugs that are otherwise destroyed in the liver to exert systemic
effects
Essentially neutral pH and lack of buffering capacity of the rectal fluid
The form in which a drug
is administered will not generally be chemically changed by the environment
Lipid-water solubility
An important consideration in the selection of the suppository base and in
anticipating drug release; Example: Lipophilic drug distributed in a fatty base in low concentration has less tendency to escape to the surrounding aqueous environment than a
hydrophilic substance in that base
Particle size
Particle size of drug affects dissolution; the smaller the particle, the more readily
the dissolution and the greater the chance for absorption
Nature of the base
Must be capable of melting, softening or dissolving; ideal characteristics:
Non-toxic, non-irritating and compatible with the incorporated drug
Suppository bases
Play an important role in the release of the medication they hold and, therefore, in the
availability of the drug
Suppository bases Should remain
solid at room temperature but soften, melt or dissolve readily at body
temperature so that drug is fully available soon after insertion
Suppository bases: Release of drug and onset of action depend on
n liquefaction of the base, dissolution of
drug and absorption
Classification of suppository bases
- Fatty (or oleaginous) bases
- Water-soluble and water-miscible bases
- Miscellaneous bases
- Fatty (or oleaginous) bases
Perhaps the most frequently employed suppository bases, principally because
cocoa butter is a member of this group of substances
-Melt quickly at body temperature
Fatty (or oleaginous) bases example
- Cocoa Butter, NF is the fat obtained from the roasted seeds of
Theobroma cacao; it is intended to melt over a narrow temperature range (30 to 36 C) - Triglyceride mixtures; their advantage over cocoa butter is that they
do not exhibit polymorphism
Advantages of cocoa butter
Advantages: Generally, non-irritating to membrane tissues and an excellent emollient
disadvantages of cocoa butter
➢ Disadvantages: May give poor and erratic release of some drugs and exhibits
polymorphism
Polymorphism
Polymorphs usually exhibit different physicochemical properties, e.g., melting point, solubility
- If a wrong polymorph is chosen for formulation, the metastable polymorph (i.e., the
thermodynamically unstable form) can convert to more stable polymorph resulting in
changes in solubility and, ultimately, bioavailability
Water-soluble and water-miscible bases
Glycerinated gelatin
is slower to soften and mix with physiologic fluids than is
cocoa butter and therefore provides a slower release
that glycerin is hygroscopic which means that
it must protect from atmospheric moisture and
may irritate tissues because of its dehydrating effect
PEG suppositories
do not melt at body temperature but rather dissolve in
mucosal fluids; thus, it need not be formulated to melt at body temperature
• Permits a slow release of medication from base
Miscellaneous bases
Mixtures of oleaginous and water-soluble or water-miscible materials
Oil-soluble drug:Oily base
Slow release; poor escaping tendency
Water soluble drug:Oily base
Rapid release
Oil soluble drug:Water-miscible base
Moderate release
Water soluble drug:Water-miscible base
Moderate release; based on diffusion; all water soluble
Suppositories are prepared by:
- Molding from a melt
2. Hand rolling and shaping
Vaginal inserts that are tablets are prepared
by compression
The method most frequently employed both on a small scale and an industrial scale
today is
molding
Molding steps include:
- Melting the base
- Incorporating medicaments
- Pouring the melt into molds
- Allowing the melt to cool and harden
- Removing the suppositories from the mold
Which bases are suitable for preparation by molding
Cocoa butter, glycerinated gelatin, polyethylene glycol and most other bases
Packaging and storage
Most commercial suppositories are individually wrapped in either foil or plastic
- Some suppositories are packaged in a continuous strip, separated by tearing along
perforations
• Commonly packaged in slide boxes or in plastic boxes
• Label includes the route to be used
• It is necessary to maintain them in a cool place
All of the following are characteristics of cocoa butter suppositories,
except:
A. Solid at room temperature, but melt quickly at body temperature
B. Demonstrate good emollient properties
C. Immiscible with body fluids
D. Fat-soluble drugs are rapidly released from them
*D. Fat-soluble drugs are rapidly released from them
Which of the following is not an advantage of the rectal route?
A. Useful for administering drugs that irritate the stomach
B. Effective for treating nausea and vomiting
C. Avoidance of systemic drug absorption
D. Partial avoidance of first-pass metabolism
*C. Avoidance of systemic drug absorption
Typically, rectal suppositories intended for pediatric use weigh approximately A. 1 g B. 2 g C. 3 g D. 4 g
*A. 1 g
Does 0.1 g of Drug X (density factor = 2) displace more cocoa butter than 0.2 g of Drug Y (density factor = 5)?
A. Yes
B. No
A. yes
- 1 g / 2 = 0.05 g displaced
- 2 g / 5 = 0.04 g displaced
