Exam 2 - Powerpoint 5 (Suppositories)

Question 1

Suppositories info

Answer 1

Solid dosage forms intended for admin via any of several body orifices, namely the rectume, vagina, or urethra where they exert local or systemic effects

they either melt, soften or dissolve in body cavity

shape and size should not cause discomfort

Should be retained for a required period of time

Question 2

Suppositories Advantages

Answer 2

Admin drugs to infants/small children or those who cant take meds orally

Severely debilitated patients, post operative people who cannot be admin oral med

Patient suffering from severe nausea or vomiting

Those for whom the parenteral route might be unsuitable

Large dose drugs easier to admin than orally

Mask unpleasant taste or smell

Preferred for drugs that irritate oral or gastric mucosa when taken orally

Question 3

Suppositories for local action

Answer 3

Drug is intended to remain in area where it will have effect

Ex.
Rectal suppository - Hemorrhoids
Vaginal Suppository - Bacterial vaginosis

Question 4

Suppositories for systemic action

Answer 4

Advantages:
Partially avoid 1st pass metabolism
Drugs destroyed or inactivated by pH or enzymatic activity of the stomach are ideal candidates

Mucous membranes of rectum or vagina permit absorption of soluble drugs

Rectum well-vascularized (hemorrhoidal veins)

Vagina is not as frequently used as rectum for delivering drugs systemically

Question 5

Physical Factors of Drug Absorption from Rectal Suppositories

Answer 5

Human rectum:
12-20 cm in length
Contains 2-3ml of mucus fluid
No villi or microvilli present
Abundant vascularization

Question 6

Physiologic Factors of Drug absorption from Rectal Suppositories

Answer 6

Colonic content - interfere with interaction of drug and the absorbing surface

Circulation route, drugs absorbed rectally bypass portal circulation and lymphatic circulation assists rectal absorption

pH (neutral) and lack of buffering capacity of rectal fluids = drugs don’t change chemically

Question 7

Physiochemical Factors of Drug absorption from Rectal Suppositories

Answer 7

Nature of suppository base
Lipid-water solubility
Particle size

Question 8

Nature of suppository base

Answer 8

Ability to melt, soften or dissolve at body temp

Ability to release the drug substance

Ability to spread, will increase surface area of mucosa covered by drug

Question 9

Lipid-water solubility

Answer 9

Lipid-water partition coefficient of the drug is an important consideration in the selection of suppository based to be used

Ex. Lipophilic drug distributed in a fatty base in low conc will not escape to aqueous surroundings as well as a hydrophilic drug

Question 10

Particle Size

Answer 10

Size of drug particle influences rate of dissolution and its availability for absorption

In general, smaller particles have higher dissolution rates and absorption rates

Question 11

Classification of suppository bases

Answer 11

Fatty or Oleaginious

Water-soluble and water miscible bases

Question 12

Fatty or Oleaginous Base

Answer 12

Cocoa Butter/ Fatty Base

Synthetic Triglyceride Mixtures

Question 13

Water-soluble and water miscible bases

Answer 13

Glycerinated Gelatin

Polyethylene Glycol Polymers

Question 14

Cocoa Butter, NF (Theobroma Oil)

Answer 14

Roasted from seeds of Theobroma Cocoa

Softens at 30C, melts rapidly between 30-36C

Exhibits polymorphism with rapid heating/cooling (Beta Form most stable)

You need to heat it gradually and then cool it, if too quickly Beta form gets destroyed

Question 15

Glycerinated Gelatin Base used in

Answer 15

Urethral + Vaginal Suppositories, not rectal (bc draws out water)

Question 16

Glycerinated Gelatin Base Formulation

Answer 16

Glycerin 70 parts, Gelatin 20 parts, Water +Drug = 10 parts

Dissolve/suspend drug in water, mix with glycerin; add to gelatin slowly.

Apply low heat to melt gelatin, gentle stirring…pour on mold, store in airtight containers (hydroscopic)

Question 17

Polyethylene Glycol Suppository Base

Answer 17

PEG available in varying molecular weights
Melting point varies as function of MW

PEG 300 = -15 to -18 C
PEG 1000 = 37 - 40 C
PEG 8000 = 60 - 62 C

Water-soluble and slowly dissolve in body fluids; stable

Question 18

Suppository Excipients

Answer 18

Stiffening Agents
Surfacants
Suspending Agents
Disintegrants
Preservatives

Question 19

how to make Suppository

Answer 19

Molding

Melt Base + Drug
If needed, lube mold with small amount of mineral oil or glycerin
Pour melted mix into mold, overfill
Allow melt to cool and congeal
Remove from mold and scrape off excess

Question 20

Suppository Compounding hints

Answer 20

Rule of Excess - Prepare 10% overage to allow for loss

Mold Capacity and Density Factors must be known

Adjustments in amount of base must be made based on target weight and density of ingredients added to base

Question 21

Rectal Suppositories

Answer 21

Cylindrical or conical shape
Adults: 2g, 1 - 1.5 inch
Infants: Half adult size

Local and systemic effects (sedatives, tranquilizers and analgesics)

Largest single use - OTC hemorrhoidal remedies

Question 22

Patient Counseling Suppositories

Answer 22

If stored at 4C, warm to room temp before insertion

Rub cocoa butter suppositories gently with fingers to melt surface for lube

Glycerinated gelatin or PEG suppositories should be moistened with water before insertion

Question 23

Vaginal Suppositories

Answer 23

Vaginal mucosa highly vascularized, avoid 1st pass

pH is acidic

Can hold 2ml of fluid

Water-soluble bases most convenient, oleaginous bases tend to “leak”

Progesterone suppositories widely used in hormone replacement therapy

Antifungal and antibacterial widely used

Question 24

Vaginal Tablets

Answer 24

Used more often than suppositories

Made by compression, ovoid shape

Plastic inserter designed for proper placement of tablet

Intended to disintegrate within vagina

Special Excipient, Mucoadhesives

Question 25

Urethral Suppositories

Answer 25

Measurement vary upon male or female

Male longer, heavier but same diameter as female

Question 26

Suppository Packaging and Storage

Answer 26

Glass or plastic containers (Glycerinated gelatin supps. packaged in glass, tightly closed)

Maybe wrapped or unwrapped (Cocoa butter individual wrapped)

Room temp or under refrigeration, moderate humidity

Question 27

Compendia Requirements Suppositories

Answer 27

Disintegration Test
Dissolution Test
Weight Uniformity
Content uniformity
Loss of drying; For packaging container integrity

Question 28

Nonsterile BUD

Answer 28

6 months if active ingredient not from manufactured product

25% remaining or 6 months (whichever shorter) if active ingredient from manufactured product