Rectal formulation should display….
- Rapid absorption
- Consistent interpatient bioavailability
- Prolonged maintenance of effective concentrations
- Minimal side effects
- Ease of dose preparation and administration
When should rectal administration be considered?
- Px is vomiting or convulsing
- Oral intake is restricted (ex: post-surgery)
How long is the rectum?
12-20 cm
What is the surface area of the rectum?
200-400 cm^2
Does the rectum contain fluid?
Small amount (3-5 mL) spread as a thin film
How long is the anal canal?
About 4 cm
What happens to drugs applied to the anal canal?
Only act locally; not absorbed systemically
What are the sections of the anal canal?
- Upper 2/3 – mucosa lined by simple columnar epithelium; supplied by superior rectal artery
- Lower 1/2 – ends are joined together by anal valves; lined by stratified squamous epithelium; relatively impermeable to drugs; supplied by inferior rectal artery
What is the superior rectal artery a branch of?
Inferior mesenteric artery
What is the inferior rectal artery a branch of?
Internal pudendal artery
Rectal route bypasses around ____ of first-pass metabolism. Why?
- 2/3
- Rectum’s venous drainage is 2/3 systemic (middle and inferior rectal vein) and 1/3 hepatic (superior rectal vein)
How are drugs absorbed in the rectum?
Paracellular, transcellular, and transport-assisted
What does absorption in the rectum depend on?
- Lipophilicity
- Molecular weight
- Water solubility
- Degree of ionization
- Formulation
Is there a wide bioavailability range for the rectal route?
Yes
What is the pH of the rectum?
- 7.2 for adults
- 9.6 for children
Does the rectum have good buffer capacity?
No
What is the difference in absorption for enemas and suppositories?
- Enemas show prompt absorption
- Suppositories show slower absorption, and depend on nature of drug used, physicochemical nature of drug, and presence of additives or excipients
What are disadvantages to the rectal route?
- Variability of absorption
- Absorption problems in px w/ diarrhea or rectal disease
- Social-cultural reluctance to use rectal dose forms
- Some drugs may cause mucosal irritation
What are the possible dose forms for the rectum? Which is most common?
- Suppository (most common)
- Solutions
- Suspensions
- Gels
- Ointments
- Foams
- Creams
How is drug released from a suppository?
Base will melt at body temp or dissolve in rectal fluid and release drug
What is the normal weight of suppositories?
- 2g for adults
- 1g for children
Are suppositories used for local effect or systemic delivery?
May be used for both
What determines the selection of a base for a suppository?
- Physicochemical nature of drug
- Desired pattern of drug release
What properties of a base are required for a suppository?
Should be solid at room temp and either melt at body temp or dissolve
