Rectal and viginal delivery

Question 1

Rectal administration

Answer 1

-used when oral route is compromised eg. infant unable to swallow tablet
-targetted delivery reduces side effects

not suitable for oral administration
-unstable at low pH/ GI enzymes
-large first pass metabolism
-unacceptable taste
-Gastric irritation
-high dose required

Question 2

Rectal delivery

Question 3

Rectal delivery

Answer 3

-may avoid first pass metabolism
-3 veins: lower and middle veins drain into systematic circulation directly
-smooth walls - no villi
-region extensively drained by the lymph system

Question 4

rectal delivery absoprtion

Answer 4

absoprtion occurs through the mucus membrane via passive diffusion, unless a penetration enhancer has been used

Question 5

physiological factors affecting absorption

Answer 5

-mucus - 3ml spread over 300cm2
-little buffer capacity - pH 7.5
-contents of rectum
-motility of rectal wall
-patient-to-patient variation in absoprtion

Question 6

rectal durg forumlations

Answer 6

-suppositries
-ointments, creams
-enemas
-tablets, soft gelatin capsules

Question 7

is rectal delivery local or systematic

Answer 7

-can be used for both local and systematic treatment
local - haemorrhoids, laxatives
systematic - pain, asthma, epilipsy

Question 8

disadvantages of rectal delivery

Answer 8

-drug absorption can be slow, incomplete, unpredictable
-higher inter-patient variability
-inconvenient
-drug may irritate the rectum
-large scale production issues
-acceptability can be an issue

Question 9

patient acceptability - rectal

Answer 9

-usppositries are popular route of drug administration in europe
-sometimes suppositries are less acceptable due to cultural issues
-useful in developing countries, reduction in side effects and little training required compared to IM/IV

Question 10

suppositry manufacture

Answer 10

-drug is uniformly distributed in a vehicle or base
-bases can be fatty or water soluble
-drug should be insouble in base used
-release due to melting or dissolution of suppositry depending on base used
-melting point of suppositry should be around 37°.

-dose: limited to prevent aggregation
-additives: surfactants to increase wetting. asorbents, lubricants, preservatives

Question 11

choice of base - suppositry

Answer 11

-bland and inert
-compatible with other ingridients
melt, dissolve or disperse at or just below body temp
-stable
-good moulding properties
-readily release active ingridient
-easily melted with rapid solidification

Question 12

Types of bases

Answer 12

fatty bases - thebroma oil
water soluble bases - polythylene glycol (PEG)
macrogols
glyecerol-gelatin

Question 13

absoprtion enhancers

Answer 13

-potential for peptides and proteins to be administred by rectal route as no peptidases present
-sodium salicylate can improve rectal absoption of theophyline - interaction of enhancer with calcium and magensium ions located in rectal membrane. calcium ions are needed to presrve tight cell junctions. interactions of enhancer may cause temporart change in membrane integrity - increases permeability
-polysorbate 8o and sodium lauryl sulphate
-long term use can lead to irritation and damage to the rectum

Question 14

formulation

Answer 14

drug solubility - low water content of rectum
rate of release - can be controlled through choice of base
drug particle size: agglomeration or precipitation
other additives may affect melting point

Question 15

suppositry calculationsm (1)

Answer 15

1. calculate the mould calibration curve
2. find the displacement value of the drug
3. displacement: the volume of a fluid (as water) displaced by a floating body (as a ship) of equal weight
4. calculate the eaxact quantities ofn durg and base required

Question 16

suppositry calculations (2)

Answer 16

-always calculate for 2 excess per 6 suppositories

(number of suppositories x mould calibration) x drug strength = total weight of drug

1/displacement value x total drug weight = base displaced by drug

(number of suppositories x mould calibration) - weight of base displaced by drug = actual wight of base required

Question 17

Tetsing

Answer 17

-weight, melting point, mechanical strength and dissolution testing
-in vitro release - difficult to correlate with in vivo situation, dialysis bag or flow method

Question 18

future advances

Answer 18

prolong drug retention through use of bioadhesive, viscosity enhanced formulations eg. thermo sensitive in-situ gels
-dividable stick shaped suppositories
-disintegrating excipients
-bioadhesive microspheres
-emulsions
-vaccinations

Question 19

vaginal delivery

Answer 19

both local and systematic drug delivery
-Thrush, HRT, Spermicidal agents

dosage forms: creams, ointments, pessaries, tablets, solution, sprays, rings and foams

Question 20

advantages of vaginal route

Answer 20

-large surface area
-rich blood supply
-low metabolic activity and pH 4
-ease of administration
-prolonged retention

Question 21

disadvantages of vaginal route

Answer 21

-limited to potent molecules
-limited moisture - local irritation
-hormone dependent changes
-absoprtion can be unpredictable

Question 22

labelling/councelling vaginal rectal

Answer 22

-store in cool place
-for rectal/vaginal use only
-do not swallow
-unwrap before use
-insert pointed end first
-retain by lying on side