Rectal delivery Flashcards
What are the problems with oral drug delivery?
patient could have problems with their GIT, could be nauseous or be postoperative
patient could be unconscious = cannot cooperate
patient could be very old, young or mentally disturbed
What is the rectum?
the rectum is part of the colon
- forms the final 150-200 mm of GIT
consists of the
- anal canal
- ampulla (80%) = expanded section where faeces are stored
is a hollow organ with smooth surface because of the absence of villi
only has three folds representing rectal valves.
rectal wall is composed of one thick epithelium layers containing cylindrical cells and goblet cells secretes mucus.
separated from the outside world by a circular muscle
- anus.
Where are drugs absorbed through in the rectum?
there are 3 main veins
inferior and middle haemorrhoidal = lower part of rectum
- passes to the inferior vena cava
- takes drugs straight into blood circulation
superior haemorroidal = upper part of rectum
- passes to the portal vein
- passes to the liver where it is metabolised (primary site of metabolism)
bioavailability from upper part will be low because of first pass elimination
What is the difference between shallow and deep suppository insertion into the rectum?
shallow suppository insertion
- taken up by the inferior and middle haemorroidal vein
- taken straight into systemic circulation (blood) by the inferior vena cava
deep suppository insertion
- taken up by the superior haemorroidal vein
- taken into the liver to be metabolised by the portal vein
How are drugs released from the rectal dosage forms?
after insertion of the dosage form (suppository)
- it will either melt or dissolve in the rectal fluid
volume of the rectal fluid is small and the suppository vehicle will attract water by osmosis from the surrounding (unpleasant sensation) to get dissolved
drug will leave the vehicle by the rectum movement and then dissolve in rectal fluid.
What are the physiological factors affecting rectal absorption? What are drug related factors affecting rectl absorption?
physiological factors
- quantity of fluid available = in the rectum
- properties of rectal mucus = viscosity
- contents of rectum
- motility of rectal wall = may cause leakage depending on motility
drug related factors
- solubility in water and vehicle = not suitable for very hydrophilic (unpleasant sensation by osmosis) or very low-water soluble drugs (poor dissolution)
= higher solubility means greater dissolution
= tamoxifen
- particle size = 50-100μm
- pKa
What drugs are suitable for rectal delivery?
suitable for peptide-like drugs
- the absence of esterase and peptidase enzymes enhance the stability of these peptides
compared to oral delivery where they had poor suitability
What are the uses of rectal drug delivery?
local
systemic
local
- treatment of haemorrhoids and relief of its symptoms (itching and pain)
- active ingredients include = vasoconstrictors, local anaestheics, astringents and anti-inflammatory
- treatment of constipation = active ingredients include bisacodyl, glycerin
systemic
- analgesic drugs
= most common use
= various opioids (morphine) have been used rectally to treat cancer pain but only 30-40% bioavailable when taken orally
- anti-asthmatics
- anti-inflammatory drugs = paracetamol
- anti epileptic drugs = diazepam rectubes®
What are the advantages of rectal delivery?
suitable for drugs liable to degradation in GIT
= peptides and esters
partially avoid hepatic first pass elimination
= if taken by the inferior and middle haemorroidal veins to the inferior vena cava
can accommodate small and large doses
suitable for children who are unable to tolerate oral doses
suitable for vomiting and nauseous patients
What are the disadvantages of rectal delivery?
patient compliance is poor
- especially in long term treatment
upward movement of drug increases first pass effect
- depends on shallow or deep insertion
drug absorption is slower
- lower SA
suppositories can leak
- due to rectal motility
What are suppositories?
suppositories are the most commonly used rectal dosage forms
- are single dose preparations with a shape, volume and consistency appropriate for rectal administration
- come of different shapes and sizes = 1-4 g
What are the requirements of an ideal suppository base/vehicle?
suppository vehicle should melt or disperse at body temperature = below 37 degrees Celsius
should be non-irritating
physically and chemically stable
pharmacologically inert
compatible with range of drugs
convenient to handling during manufacturing and storage
have good viscosity (as it affect flow into the moulds during manufacturing and spreading into the interface with the rectal fluid for release and absorbance).
What are the types of suppository vehicles?
fatty vehicle
water-soluble vehicle
What are fatty vehicles? What are the types? What are their properties?
semi-or fully synthetic
= Cocoa butter (theobroma oil) is a very commonly used base but not anymore because\
- has polymorphic behaviour = has different crystalline forms with different melting points
- low softening point
- chemical instability
- poor water-absorptive power (less decomposition)
- expensive
new fatty bases have become available (Witepsol, Fattibase, Cotmar)
- mixtures of natural and synthetic vegetable oils
consists of mixed trigylcerides, waxes and fatty alcohol
What is glycerinated gelatin? What is its properties?
glycerinated gelatin = glycerol-gelatin
- is a mixture of gelatin, glycerol and water
when mixed they form
- translucent, gelatinous mixtures which disperse in rectum
ratio of mixing these components affect the dispersion time and hence the duration of action
- higher content of gelatin makes the formulation more rigid and longer acting)
needs to be stored in a closed container as they are hygroscopic
- absorb moisture from the air
