Suppositories, Inserts, and Medication Sticks

Suppositories

• solid dosage forms in which one or more APIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into body orifices to provide local or systemic effect

• generally employed to promote defecation, introduce drugs into the body, treat anorectal diseases

• have various shapes and weight

supponere

Latin word for suppositories meaning “to place under”

Rectal suppositories

• usually about 32mm (1.5 inch) long, are cylindrical, and have one or both ends tapered

Rectal Suppositories for Adult Use

weigh about 2 g when cocoa butter (theobroma oil) is employed as the base

Rectal Suppositories for use by infants and children

about half the weight and size of the adult suppositories and assume a more pencil-like shape

Inserts

solid dosage forms inserted into a naturally occurring (nonsurgical) body cavity other than the mouth or rectum, including the vagina and urethra

Vaginal inserts

formerly called suppositories or pessaries that are usually globular, oviform, or cone shaped and weigh about 5g when cocoa butter is the base

Urethral inserts

also called bougies that are slender, pencil-shaped suppositories intended for insertion into the male or female urethra

male urethral suppositories

• 3 to 6 mm in diameter and approximately 140 mm long

• 4 g in weight when cocoa butter is employed as the base

female urethral suppositories

• 70 mm long

• weighing about 2 g when made of cocoa butter

Medication sticks

• solid dosage forms inserted into a naturally occurring convenient forms for administering topical drugs

• cylindrical in shape and generally range from 5 to 25 g

• generally packaged in an applicator tube for topical administration

first-pass effect

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

a = ?

gastric degradation

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

b = ?

larger doses

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

c = ?

irritating effect

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

d = ?

unpleasant tasting or smelling drugs

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

e = ?

nausea and vomiting

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

f = ?

upper gastrointestinal tract

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

g = ?

taste or odor

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

h = ?

rapid drug

Advantages of rectal administration:

a. avoiding, at least partially, the ______________

b. avoiding the breakdown of certain drugs that are susceptible to _____________

c. ability to administer somewhat __________ of drugs

d. ability to administer drugs that may have an _______________ on the oral or gastrointestinal mucosa when administered orally

e. ability to administer ___________________________ whose oral administration is limited - in children, the rectal route is especially useful

f. in patients experiencing ________________ or when the patient is unconscious

g. presence of disease of the ________________________ that may interfere with drug absorption

h. objectionable ___________________ of a drug

i. achievement of a ____________ effect systemically

i = ?

dosage

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

a = ?

expensive

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

b = ?

variable effectiveness

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

c = ?

narrow therapeutic margin

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

d = ?

bullet-shaped suppository

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

e = ?

defecation

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

f = ?

smaller

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

g = ?

fluid content

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

h = ?

microflora

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

i = ?

greater than or less than

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

j = ?

anatomic-physiologic and physicochemical

Disadvantages of suppositories:

a. perceived lack of flexibility regarding ________ of commercially available suppositories

b. if made on demand, they may be __________

c. safe but exhibit _____________________

d. different formulations of a drug with a _________________________ cannot be interchanged without risk of toxicity

e. ________________________________________ after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon (should not be used at bedtime)

f. ____________ may interrupt the absorption process of the drug

g. absorbing surface area of the rectum is much _________ than that of the small intestine

h. _____________ of the rectum is much less than that of the small intestine

i. possibility of degradation of some drugs by the ________ present in the rectum

j. dose of a drug required may be ___________________ the dose of the same drug given orally

k. factors affecting rectal absorption: __________________________________ factors of the drug and the base

k = ?

Local action

once inserted, the suppository base melts, softens, or dissolves, distributing its medicaments to the tissues of the region

Rectal suppositories

relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions

Vaginal suppositories or inserts

contraceptives, as antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen

Sticks

hydration/emollient, antibacterial, sunscreen, antipruritic, and other uses

Systemic action

for systemic effects, the mucous membranes of the rectum and vagina permit the absorption of many soluble drugs

Circulation route

Physiological factors and drug effect:

• drugs absorbed rectally can bypass the portal circulation during their first pass into the general circulation

pH and lack of buffering capacity of the rectal fluids

Physiological factors and drug effect:

• pH of the rectal fluid is generally in the range of 7.2 to 7.4; negligible buffer capacity

• form in which the drug is administered will not generally be chemically changed by the rectal environment; therefore, the pH of the medium may be determined by the characteristics of the drug

Colonic content

Physiological factors and drug effect:

• a drug will obviously have greater opportunity to make contact with the absorbing surface of the rectum and colon in the absence of fecal matter

Lipid–water solubility

Physicochemical factors and drug effect

• lipid–water partition coefficient of a drug

• lipophilic drug distributed in a fatty suppository base in low concentration has less tendency to escape to the surrounding aqueous fluids than a hydrophilic substance in a fatty base

• the more drug a base contains, the more drug will be available for absorption

Particle size

Physicochemical factors and drug effect

• the smaller the particle, the greater the surface area, the more readily the dissolution of the particle, and the greater the chance for rapid absorption

• avoid a too fine particle size – high increase of the viscosity of the melted excipient that can result from the use of excessively small particles and possible difficulties in flow during production

Nature of the Suppository Base

• if the base interacts with the drug to inhibit its release, drug absorption will be impaired or even prevented

• if the base irritates the mucous membranes of the rectum, it may initiate a colonic response and prompt a bowel movement, eliminating the prospect of complete drug release and absorption

Classification of Bases

• should be physically and chemically stable, nonirritating, nontoxic, non-sensitizing, chemically and physiologically inert, compatible with a variety of drugs, stable during storage, and esthetically acceptable

• fatty or oleaginous, water-soluble or water miscible, miscellaneous bases

Fatty or oleaginous bases

most frequently employed suppository bases

Cocoa Butter, NF

Fatty or Oleaginous Bases:

• fat obtained from the roasted seed of Theobroma cacao

• ideal suppository base

• mixed triglycerides of oleic, palmitic, and stearic acids

34 - 35

melting range of cocoa butter in degrees celsius

Fattibase

Fatty or Oleaginous Bases:

• triglycerides from palm, palm kernel, and coconut oils with self-emulsifying glyceryl monostearate and polyoxyl stearate

35.5 - 37

melting range of fattibase in degrees celsius

Polybase

Fatty or Oleaginous Bases:

• a homogenous blend of PEGs and polysorbate 80

60 - 71

melting range of polybase in degrees celsius

Suppocire OSI

Fatty or Oleaginous Bases:

• eutectic mixtures of mono-, di-, triglycerides derived from natural vegetable oils, each type having slightly different properties

33-35

melting range of Suppocire OSI in degrees Celsius

Wecobee W

Fatty or Oleaginous Bases:

• triglycerides derived from coconut oil

31.7-32.8

melting range of Wecobee W in degrees Celsius

Witepsol H15

Fatty or Oleaginous Bases:

• Triglycerides of saturated fatty acids C12-C18 with varied portions of the corresponding partial glycerides

33-35

melting range of Witepsol H15 in degrees Celsius

Glycerinated gelatin suppositories

Water-soluble and water-miscible bases:

• slower to soften and mix with the physiologic fluids than is cocoa butter

• provides a slower release

• hygroscopic

• may have a dehydrating effect and irritate the tissues upon insertion

Polyethylene glycol suppositories

Water-soluble and water-miscible bases:

• do not melt at body temperature but rather dissolve slowly in the body’s fluids

• slower release of the medication from the base once the suppository has been inserted

nature and form

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

a = ?

physical state, particle dimensions, and specific surface

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

b = ?

various bases

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

c = ?

adjuvants

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

d = ?

dosage form

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

e = ?

pharmaceutical procedures

Formulation variables:

a. _____________ of the active principle

b. ____________________________________ of the product

c. solubility of the drug in ___________

d. presence or absence of ___________ added to the active principle

e. nature and type of ____________ in which the active principle is incorporated

f. __________________________ used in the preparation of the dosage form

f = ?

Viscosity

Formulation Variables:

• causes the drug to diffuse more slowly through the base to reach the mucosal membrane for absorption

• release rate of the drug may be slowed if this of is very high

Brittleness

Formulation Variables:

• results when the percentage of non-base materials exceeds about 30%

• shock cooling

• causes fat and cocoa butter suppositories to crack

• suppositories should not be placed in a freezer

Volume Contraction

Formulation variables:

• bases, excipients, and active ingredients generally occupy less space at lower temperatures than at higher temperatures

slow release; poor escaping tendency

Formulation variables: Drug Release Rates

• Drug: Oil-soluble drug

• Base Characteristics: Oily Base

• Approximate Drug Release Rate: ?

Rapid Release

Formulation variables: Drug Release Rates

• Drug: Water-soluble drug

• Base Characteristics: oily base

• Approximate Drug Release Rate: ?

Moderate Release

Formulation variables: Drug Release Rates

• Drug: Oil-soluble drug

• Base Characteristics: Water-miscible base

• Approximate Drug Release Rate: ?

Moderate release; based on diffusion; water soluble

Formulation variables: Drug Release Rates

• Drug: Water-miscible drug

• Base Characteristics: Water-miscible base

• Approximate Drug Release Rate: ?

Molding

Preparation of Suppositories:

1. melting the base

2. incorporating any required medicaments

3. pouring the melt into molds

4. allowing the melt to cool and congeal into suppositories

5. removing the formed suppositories from the mold

Hand Rolling and Shaping

Preparation of Suppositories:

• with ready availability of suppository molds of accommodating shapes and sizes, there is little requirement for today’s pharmacist to do this

Quality control

• identification, assay, and in some cases, loss on drying

• disintegration, and dissolution

• stability

• observation for excessive softening and oil stains on packaging

• compounded suppositories

• calculations of theoretical and actual weight and weight variation, color, hardness, surface texture, and overall appearance

glycerin or glycerinated gelatin suppositories

Packaging and storage

• packaged in tightly closed glass containers to prevent a change in moisture content

• stored at controlled room temperature (20°C to 25°C or 68°F to 77°F)

prepared from cocoa butter base

Packaging and storage

• individually wrapped

• separated in compartmented boxes to prevent contact and adhesion

• stored below 30°C (86°F) and preferably in a refrigerator (2°C to 8°C or 36°F to 46°F)

prepared from base of polyethylene glycol

Packaging and storage

• stored at usual room temperatures

containing light-sensitive drugs

Packaging and storage

• individually wrapped in an opaque material such as a metallic foil

Fungal Contamination

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Odor

• Causes: ?

• Examples:

Suppositories with vegetable extracts

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Odor

• Causes:

• Examples: ?

Discoloration due to Oxidation

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Color

• Causes: ?

• Examples:

Suppositories with tartrazine yellow aqueous solution

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Color

• Causes:

• Examples: ?

Incorrect Temperature during Storage

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Shape

• Causes: ?

• Examples:

Suppositories with Essential Oils

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Shape

• Causes:

• Examples: ?

Whitening

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Surface Condition

• Causes: ?

• Examples:

Suppositories with Vegetable Extracts or Caffeine Base Suppositories

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Surface Condition

• Causes:

• Examples: ?

Loss of Volatile Substances

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Weight

• Causes: ?

• Examples:

Suppositories with camphor, menthol, etc.

Physical Stability: Major Changes in Suppository Characteristics Due to Natural Aging and the Causes

• Modification: Weight

• Causes:

• Examples: ?

Chemical stability

• hydrolysis

• epimerization

• decarboxylation

• dehydration

• oxidation

• photochemical decomposition

• pH effect

6 months

Microbiological stability: Beyond-use dating for ccmpounded suppositories

a. if the product is prepared from USP/NF ingredients, a beyond-use date of __________ is appropriate (unless evidence is available to support other dating)

b. if the stability of a compounded water-containing preparation is unknown and there is no other supporting data for an alternate beyond-use date, then a beyond-use date of ______________________________ can be used

a = ?

14 days when stored in a refrigerator

Microbiological stability: Beyond-use dating for ccmpounded suppositories

a. if the product is prepared from USP/NF ingredients, a beyond-use date of __________ is appropriate (unless evidence is available to support other dating)

b. if the stability of a compounded water-containing preparation is unknown and there is no other supporting data for an alternate beyond-use date, then a beyond-use date of ______________________________ can be used

b = ?

expiration date

Microbiological stability: Expiration dating for manufactured suppositories

a. commercially manufactured suppository must bear an _____________ determined by appropriate stability testing

b. ________________ is a major indication of instability in suppositories

c. general rule: suppositories should be stored in a _____________

a = ?

excessive softening

Microbiological stability: Expiration dating for manufactured suppositories

a. commercially manufactured suppository must bear an _____________ determined by appropriate stability testing

b. ________________ is a major indication of instability in suppositories

c. general rule: suppositories should be stored in a _____________

b = ?

refrigerator

Microbiological stability: Expiration dating for manufactured suppositories

a. commercially manufactured suppository must bear an _____________ determined by appropriate stability testing

b. ________________ is a major indication of instability in suppositories

c. general rule: suppositories should be stored in a _____________

c = ?