Rectal & Vaginal Drug Delivery

Question 1

What is the rectal epithelium composed of?

Answer 1

Cylindrical cells and goblet cells that secrete mucous

Question 2

What are the three situations where rectal drug delivery is appropriate as an alternative route

Answer 2

Patient is unable to make use of oral route
When a patient is unconscious and uncooperative
When a drug compound is less desirable for oral delivery

Question 3

What limits the use of suppositories as a major drug administration route?

Answer 3

Traditions and cultures

Question 4

What are a few disadvantages of rectal drug delivery?

Answer 4

Slow and incomplete drug absorption
Inter-subject variation
Stringent storage conditions to maintain quality

Question 5

What are the more common uses for suppositories?

Answer 5

Local effects; control pain, itching and constipation
They include astringents, antiseptics, laxatives, local anaesthetics, vasocontrictors and anti-inflammatories
Systemic effects; antihistamines, antirheumatics and analgesics

Question 6

Name four commercially available suppository products and their intended use.

Answer 6

Naprosyn: naproxen suppository; for OA, RA and dysmenorrhea
Cafergot: alpha blocker; migraine therapy
Salofalk: sulfasalazine; IBS
Dilaudid: hydromorphone; Antitussive and analgesic

Question 7

What are the three veins in the rectum and where do they lead?

Answer 7

Lower and middle haemorrhoidal veins; drain directly into the general circulation
Upper haemorrhoidal drains into the portal vein and flows to liver
*should keep suppository lower to have higher bioavailability

Question 8

Why is a suppository that melts, more optimal than a suppository that dissolves?

Answer 8

Rectal fluid is very small, leading to incomplete dissolution of suppository. Water is attracted to suppository due to osmotic effect

Question 9

What is the main method of drug absorption?

Answer 9

Passive diffusion.

Question 10

What is critical in maintaining ideal concentration gradient for diffusion?

Answer 10

The properties of rectal fluid (composition, volume, viscosity and surface tension)

Question 11

Why is the stability of peptide-like drugs good in the rectum?

Answer 11

No esterases or peptidases

Question 12

Define suppositories.

Answer 12

A solid dosage form that is inserted into the rectum, vagina or the urethra for drug delivery. It then soften, melts or dissolves in the body to release drug or local or systemic effect.

Question 13

What are the two classes of suppository vehicles used as bases

Answer 13

Oil base (glyceride-type fatty compounds, lipophilic)
Water-soluble base (glycerol-gelatin mixtures of PEGs, hydrophilic)

Question 14

What base is normally used for laxative purposes or in vaginal therapy?

Answer 14

Water-soluble

Question 15

List the three general requirements of the vehicles.

Answer 15

1) Should either melt (melting range of 37 degrees) or dissolve and mix with available rectal fluid.
2) Exhibit sufficient physiochemical characteristics for industrial scale production (good flowability, viscosity, fast solidification, and allow uniform distribution of active ingredients)
3) Chemically and physically stable during storage (no incompatibility with active or additive ingredients)

Question 16

This base is no longer used due to its polymeric behaviours, chemical instability, low softening point and high cost.
What is now used?

Answer 16

Cocoa butter has been replaced with semi- or fully synthetic triglycerides which have higher melting points and solidifying range

Question 17

What determines the maximal attainable concentration for rectal drug absorption?

Answer 17

Whether it is in suspension or solution within the vehicle.

Question 18

What occurs if a drug has a high vehicle to water partition coefficient?

Answer 18

Has a tendency to stay in the vehicle and show a low drug release rate.

Question 19

What is required for penetration through rectal membrane?

Answer 19

Lipid solubility

Balance is necessary to achieve optimal dug delivery rate and absorption extent

Question 20

What can lead to drug agglomeration in the suppository and what would result?

Answer 20

When the particles are too big or not well wetted by vehicle.
This results in content uniformity problems and separation of the final product.

Question 21

What do small drug particles improve?

Answer 21

Dissolution and absorption by getting in to solution more readily.
Reduce potential for local mechanical irritation

Question 22

What is the optimal particle size range and what are the benefits the low and high range given?

Answer 22

50-100microm

50: benefit drug absorption through molten vehicle
100: safe against sedimentation during preparation

Question 23

As the number of particles _________, the potential for drug agglomeration will ________.

Answer 23

Increase, increase

Question 24

What is the general drug content range?

Answer 24

Within 0.1- 40%

And the size ranges from 1-4g

Question 25

What is the important consideration when using additives?

Answer 25

The potential influence of formulation changes on drug release characteristics

Question 26

How can you increase the viscosity of a suppository?

Answer 26

1-2% of colloidal silicon oxide or aluminum monostearate creates a gel-like system with slower drug release rate.

Question 27

What is the purpose of the use of surfactants?

Answer 27

Emulsifying, wetting, deglomerating and penetration enhancing.
But each surfactant is assessed separately in association with the drug candidate.

Question 28

Due to suppositories low melting point, how are most suppositories packaged and stored?

Answer 28

Individually in plastic (PVC) or aluminum foil packs

Store under cool, dry conditions, protect against extreme temperature, moisture and oxygen

Question 29

List the other rectal dosage forms.

Answer 29

Effervescent tablets
Soft-shell capsules
Microenemas (solution/dispersions of drug in small volumes)

Question 30

What are the two main uses for vagina/uterus drug administration?

Answer 30

Contraceptive steroids

Metronidazole

Question 31

How is drug absorption in the vagina normally achieved?

Answer 31

Passive diffusion, directly into systemic circulation (no first pass metabolism)

Question 32

How is it possible to maintain a relatively steady blood concentration for prolonged period of time with vaginal delivery?

Answer 32

Most vaginal devices are sustained and controlled release

Question 33

Describe vaginal devices for contraceptive purposes.

Answer 33

Polymeric matrix, deliver drug content at a fixed dose rate by dissolution/partition mechanisms. Device can deliver at zero-order rat for extended time

Question 34

What are the types of dispersion in vaginal devices?

Answer 34

Homogenous dispersion
Sandwich dispersion
Ring dispersion
Core dispersion