AP - Rectal and Vaginal Drug Delivery Flashcards
What is the main dosage form for rectal and vaginal drug delivery?
Suppository.
Define suppository.
A solid dosage form intended for insertion into body orifices where it melts, softens or dissolves and exerts local or systemic effects.
State at least 5 advantages of suppositories.
- Patients who cannot take drugs orally (nauseous, post -op, elderly) can use this
- Infants and geriatrics can use this
- Can be have systemic or local effects
- Avoids first pass metabolism
- Does not cause gastric irritation
- Drug stability in gastric pH is no longer an issue
- Gut enzymatic stability no longer an issue
- Can be used for either prolonged or sustained action.
State at least 5 disadvantages of suppositories.
- Patients who have physical impairments or arthritis will find it difficult to administer these –> compliance issue
- Large scale production is difficult
- Not first choice for many conditions
- Patient to patient variation in response
- Slow and incomplete absorption
- Absorption hindered by colonic content
- Stringent storage conditions.
For both rectal and vaginal routes, state the following:
- formulation inserted in
- local or systemic
- mucus secretions
- pH (no buffering capacity)
- Extra notes
RECTAL
- rectum
- both
- around 3 ml
- 7.5
- Formulation melts/ dissolves. Additional water is drawn into rectum due to osmotic effect of formulation base (can lead to irritation)
VAGINAL
- vagina
- both
- around 4 ml
- 4
- Formulation melts/ dissolves in mucus.
What are the physiological factors affect drug absorption in the rectum?
- Quantity of mucus available
- Properties of rectal mucus (pH. water content etc)
- Contents of rectum
- Motility of rectal wall
What are the physiological factors affect drug absorption in the vagina?
- Quantity of mucus available
- Properties of mucus (pH. water content etc)
- Menstruation
What are some systemic uses of rectal suppositories?
Antiemetic e.g. Prochlorperazine
Analgesic e.g. Oxymorphone
Migraine
Antihistamine e.g. Promethazine HCl
What are some systemic uses of vaginal suppositories?
Hormones e.g. Oestrogen
What are some local uses of rectal suppositories?
Anti-inflammatory e.g. Mesalamine
Haemorrhoids e.g. Hydrocortisone
Cathartic e.g. Bisacodyl
What are some local uses of vaginal suppositories?
Contraceptive e.g. Nonoxynol-9
Formulation types for vaginal delivery that rectal delivery does not have:
pessaries, films, foams, sprays, gels.
What are some pre-formulation information we need on the drug?
Drug solubility (aqueous and non aqueous) Drug stability Drug metabolism and degradation Log P pKa Toxicity Other physics-chemical properties Choice of dosage forms
What are the different types of suppository bases?
- Fatty/ oleaginous bases
- Water-soluble/ miscible bases
- Miscellaneous bases
Summarise Fatty/ oleaginous bases.
- Hydrogenated fatty acids of vegetable oils e.g. cocoa butter, Weecobee, Fattibase, Witepsol
- Melting point = 30 - 36
- Exhibits polymorphisms
- Action: melts at body temp
Summarise water soluble/ miscible bases.
- Glycerinated gelatin, PEG (300, 400, 600, 8000)
- Melting point = -15 to 63
- Action: Dissolves and absorbed in the body
Summarise miscellaneous bases.
- Mixture of fatty and water soluble bases containing a surfactant e.g. Polyoxyethylene laurel alcohol ether
What is a displacement value?
The number of parts by weight of drug that displaces 1 part by weight of base.
Formula for the amount of base required for preparing suppositories:
N * Y = (N * D)/ (DV)
where N = number of suppositories Y = weight of mould D = weight of drug in each suppository DV = displacement value
What is the typical weight of suppositories?
1 - 4 grams
What are the 3 methods of suppositories preparation?
Melting and moulding method
Compression method
Hand rolling + shaping method
Outline the steps for the melting and moulding method
- Mix API with other ingredients
- Melt base (above its melting point)
- Mix API with molten base
- Lubricate mould (mineral oil, dimethicone etc)
- Pour into mould
- Allow to solidify (at room temp)
- Remove excess from the top (warm life/spatula)
- Remove from mould
- Pack individually
Outline the compression method
The process is carried out at room temp.
It is suitable for thermolabile API (readily destroyed or deactivated by heat).
1. Dry mix ingredients thoroughly
2. Fill and compress in a mould
Limitation = shape can only be a cylinder
What are some in process controls for suppositories?
- USP, BP
- Identification
- Assay for the drug content
- Loss on drying
- Disintegration
- Dissolution
- Packing compatibility
