Suppositories, Inserts, Medication Sticks

_____________: a solid dosage in which 1+ APIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion rectally or vaginally

suppository

1. Suppositories are medicated, _________ preparations

2. used in … (3) routes of administration

3. T or F: they provide only systemic activity

1. semisolid

2. rectal, vaginal, urethral

3. F (local and/or systemic)

Why would a drug need to be administered rectally when oral route is the most convenient? (advantages)

1. rectum is considered relatively _______ and ______

2. has low ________ _______ in comparison to other sections of GI tract

3. drugs can partially bypass the liver following systemic absorption, which reduces the hepatic _________ effect

4. achievement of a ______ drug effect systemically

1. constant, stable

2. enzymatic activity

3. first pass

4. rapid

Rectal suppositories uses: (3)

1. systemic effects → antiemetics (anti N/V), analgesics, hormones

2. treat anorectal diseases/local effects → hemorrhoids, anal fissures, infections, ulcerative proctitis, inflammation

3. promote defecation (laxatives)

Rectal suppositories DISADVANTAGES:

1. not __________ by patients and may be ________

2. some may _______ or are ________ after insertion

3. absorption may be ________

4. the “bullet shaped” suppository can _______ the anorectal site after insertion → ascend to recto sigmoid and descending colon

5. ___________ may interrupt absorption process

6. area of absorption in the rectum is _________ (_________)

7. small rectal ________ content may cause problems w drug dissolution or absorption

1. preferred, inconvenient

2. leak, expelled

3. erratic

4. leave

5. defecation

6. small, 200-400 cm²

7. fluid

1. Rectal suppositories shape = ________ or _______ and tapered/pointed at one end

2. T or F: infant rectal suppositories weigh about half as much as adult supp

3. Vaginal suppositories shape =

4. Urethral inserts/bougies shape =

1. cylindrical, conical

2. T

3. ovoid, globular, cone shaped

4. slender, pencil-shaped

_________ _________: designed to give an extended-release of medication (________ hrs)

Treatment of internal and external _________ simultaneously

rectal rocket, 4-6 hrs, hemorrhoids

Systemic action

1. The ________ _________ of the rectum permit the absorption of many soluble drugs

2. Suppositories may be used in the treatment of … (6)

1. mucous membranes

2. N/V, pain, fever, migraines, provide sedation, hormone replacement

Rectal Drug absorption

1. _______________________ → enters hepatic portal system → first-pass effect

2. _______________________ → enter systemic circulation

1. superior rectal vein

2. middle and inferior rectal vein

1. _______ ___________: severe and often fatal disease, characterized by acute onset of encephalopathy, liver dysfunction, and fatty infiltration of the liver and other viscera

2. Contraindication: aspirin and other salicylates in ___________ and ___________ w viral illness-associated fever due to possible association w ^

1. Reye syndrome

2. children, young adults <20 yo

Vaginal Suppositories and Inserts

1. systemic effect →

2. local effect →

1. hormone

2. infection, dryness, contraception, urethral inserts

Physiological factors that affect rectal drug absorption:

1. __________ __________: generally accepted that ________% of active ingredients bypass the liver and avoid the first pass effect

2. __________________

3. pH of rectal fluid ___________ and lack of ________ capacity

1. circulation route, 50-70%

2. colonic contents

3. 6.8-7.4, buffering

Physiochemical Factors that Affect Rectal Drug Absorption:

1. __________ _______

2. ^ Oil-soluble drug + oily base = __________ release

3. ^ Water-soluble drug + oily base = __________ release

4. ^ oil-soluble drug + water base = ____________ release

5. ^ water-miscible drug + water base = __________ release

6. ___________ _______ →

1. lipid-water solubility

2. slow

3. rapid

4. moderate

5. moderate → based on diffusion

6. particle size (smaller = faster dissolution)

Types of suppository bases (2):

1. fatty/oleaginous → melt

2. water-soluble/miscible → dissolve

Desirable properties of suppository bases:

1. _________ and _________ to mucous membranes

2. _________ w a variety of drugs

3. chemically and physiologically ________

4. _______ or __________ in presence of mucous secretions at body T

5. allow ________ of API

6. remain ________ on storage

1. nontoxic, nonirritating

2. compatible

3. inert

4. melt, dissolve

5. release

6. stable

Fatty or Oleaginous Bases

1. Melt in ________ minutes

2. _________ MPs than water miscible bases

3. MUST BE KEPT AT controlled _________ or __________

4. Example →

5. ^ melts at _________℃

1. 3-7

2. lower

3. room T, refrigerated

4. cocoa butter/theobroma oil

5. 30-36 (86-97F)

__________________: ability of a solid material to exist in different crystalline forms which differ in their physical properties

Cocoa butter must be slowly and evenly melted to avoid formation of unstable crystalline form

polymorphism

Water-soluble and water-miscible bases:

1. Example 1 =

2. freq used as base for ____________ suppositories for __________ local action

3. dissolves slowly in the mucous secretions in about ______ mins

4. Due to __________ (water absorbing) of glycerin → dehydrating effect and irritate tissues, thus supp should be …

5. may be used w a _________ range of drugs

1. glycerinated gelatin

2. vaginal, prolonged

3. 30-40

4. hygroscopicity, dipped in water before insertion

5. wide

Water-soluble and water-miscible bases:

1. Example 2 =

2. Dissolves in body’s _______ and do _________________

3. No _________ after insertion and preferred base for vaginal + urethral

4. Counseling →

5. Major disadvantage is their __________ w a large number of drugs

6. 300-600 Mw = _____________

7. 1000+ Mw = ____________

8. increasing Mw = ________ MP

1. polyethylene glycol PEG

2. fluids, not require refrigeration

3. leaking

4. dip in water before insertion, rectal use may cause defecating reflex

5. incompatibility

6. clear liquid

7. white waxy solid

8. inc

What bases can you use for

1. Vaginal supp =

2. rectal supp =

1. glycerinated gelatin or PEG (preferred)

2. oleaginous bases or PEG

PEG vs fatty bases

1. compatibility and stability

2. patient comfort

3. rectal suppositories

1. fatty less reactive than PEG (more stable and compatible)

2. fatty more comfortable

3. fatty preferred

Max amount of solid material that can be incorporated in a suppository is approx _______ of the blank weight (weight of one supp that contains only the base)

30%

Methods of Preparation of Suppositories

1. ________________ → most common (molding)

2. ________________ → for small number of supp to be prepared in cocoa butter base

3. ________________ → heat labile components (NOT heat stable)

1. fusion method

2. hand rolling

3. compression

Advantages of Molding

1. less __________ skill

2. ____________ and professional appearance

Disadvantages of Molding

3. _________ molds are required

4. caution when incorporating ______ _______ components

5. __________ calculations, mold ___________, or ______________ procedures are required to give accurate dose

6. Supp molds may require ___________ w ___________

1. technical

2. elegant

3. special

4. heat labile

5. density, calibrations, double-casting

6. lubrication, mineral oil

_________ ____________: when an API is added to a supp base, it will displace an amount of base as a function of its density

DF = weight of API/weight of base displaced

density factor

Compounding Suppositories

General Rule: calculate the amounts of materials needed for the preparation of one or two more suppositories than the number prescribed to compensate for the inevitable loss of some material. Alternatively, many compounding pharmacists prepare an extra ______%

10%

PACKAGING suppositories

1. Suppositories made in disposable _________ or __________ molds may be dispensed directly in the mold

2. Glycerin + PEG base supp should be packaged in __________ containers to protect from moisture

3. Oleaginous base supp not dispensed in mold usually individually ________ or _______ in compartmented boxes

4. Supp containing light sens drugs are individually wrapped in an ________ material (e.g. foil)

1. plastic, rubber

2. airtight

3. wrapped, separated

4. opaque

STORAGE temps

1. Oleaginous base suppositories =

2. Glycerinated gelatin or PEG suppositories =

1. cold T = 2-8 C / 36-46 F

2. room T = 20-25 C / 68-77 F

Physical instabilities of suppositories (7)

1. softening

2. hardening

3. drying

4. cracking

5. separation

6. polymorphs when MP is affected

7. odor of rancidity

Chemical instabilities of suppositories (7)

1. hydrolysis

2. decarboxylation

3. dehydration

4. oxidation

5. photochemical decomposition

6. pH effect

7. solid state stability

T or F:

Suppositories must contain preservatives/antioxidants because water is present in the formulations (which may support growth of microorganisms)

F (not needed, water is usually excluded)

Patient Counseling → Suppositories:

1. When supp are dispensed in foil or plastic wrapping, instruct patient to __________ wrapping before inserting supp

2. __________ conditions

3. ____________________ if compounded

1. remove

2. storage (fatty = cold, water sol = room T)

3. beyond use date

How to insert a rectal suppository

1. Insert into rectum until it passes the sphincter (how far in for infants vs adults?)

2. close legs and sit OR lie still for __________

3. avoid emptying bowels for at least ___________ (unless supp is a laxative) and avoid excessive movement/exercise

1. 0.5-1 in for infants, 1 in for adults

2. 15 min

3. 1 hr

Prescription Only Products

Rectal suppositories

1. → hemorrhoids

2. → hemorrhoids

3. → ulcerative proctitis

4. → anti-inflammatory

5. → antiemetic (prevent N/V)

6. → antiemetic

7. → migraine

8. → pain associated w ureteral spasm

9. → pain

10. → pain

1. Anusol HC - hydrocortisone acetate

2. Proctocort - hydrocortisone acetate

3. Canasa - mesalamine

4. Indocin - indomethacin

5. promethazine

6. prochlorperazine

7. Migergot - ergotamine+caffeine

8. Belladonna/Opium

9. morphine sulfate

10. hydromorphone

Prescription Only Products

Suppositories and Inserts

1. → vulvovaginal candidiasis/yeast infection

2. → bacterial vaginosis

3. → progesterone

4. → erectile dysfunction

1. Terconazole

2. Cleocin ovules - clindamycin

3. Endometrin insert

4. Muse Uretheral pellet - alprostadil

Medication Sticks

1. 2 types →

2. provide what kind of activity?

3. Easily ____________ and convenient dosage form for administering ________ medications

4. _________ and __________ purposes

5. What may be administered by medication sticks? (5)

1. soft sticks, hard sticks

2. local OR systemic

3. transportable, topical

4. cosmetic, medical

5. local anesthetics, sunscreens, oncology drugs, antivirals, antibiotics

SOFT medication sticks:

1. Prepared similarly to __________

2. clear sticks made from …

3. opaque sticks made from …

4. examples =

1. suppositories

2. sodium stearate, glycerin, and/or propylene glycol

3. petrolatum, cocoa butter, PEG

4. lip balm, deodorant, makeup

HARD Medication Sticks

1. Prepared from _______ powders that are _______ together OR fused by a _________ such as …

2. Must be _________ to be activated

3. Example =

1. crystalline, heated, binder → cocoa butter, petrolatum

2. moistened

3. styptic pencil

What rectal drug + base pair has rapid absorption?

water-soluble drug + fatty base