Oral drug delivery Flashcards
What are the advantages of oral drug delivery?
for the patient
- convenience
- not invasive
- higher compliance
for manufacture
- well established processes
- easy to manufacture
- cheap process.
high surface area available for absorption.
What are the types of formulations for oral drug delivery?
traditional
- tablets
- capsules
- soft gelatin capsules
- suspensions
- emulsions
controlled
- sustained
- extended
What is bioavailability? What are the factors affecting oral drug availability?
bioavailability
- the rate and extent of appearance of the drug into the systemic circulation
- depends on a series of process
rate limiting step - determines bioavailability
- dissolution
- absorption/permeation
- gastric emptying rate
- drug metabolism rate
What is the GIT? What are its properties?
gastrointestinal tract
- muscular tube extend from mouth to anus
- is ~ 6 m in length with varying diameter
- the luminal surface is very rough
What is mucus?
mucus = majority of GI epithelium is covered with mucus
- is a viscoelastic translucent gel
- has large water content = 95%
- acts as protective layer and mechanical barrier
- is removed by abrasion and the acidic or enzymatic breakdown
a primary component is a glycoprotein called mucin
What are the components of the GIT?
oesophagus stomach duodenum jejunum ileum colon, pH 5.5-7.8 , transit time 15-48 hours
small intestine = duodenum, jejunum, ileum
large intestine = colon
What is the oesophagus? What are its properties?
is a thick muscular layer join the oral cavity to stomach
- 250 mm long and 20 mm diameter
has mucus glands to secret mucus to lubricate food and protect lower part from gastric acid.
has pH between 6.8 and rapid transit (10-14 seconds)
What is the stomach? What are its properties?
is the most dilated part and consist of four anatomical regions
- fundus, body, antrum and pylorus.
- has a capacity of 1.5 L
- transit time = 1-5 hours
- pH = 1.8-2.5
under fasting conditions contains 50 mL of fluids
- mainly gastric fluid
contains
- hydrochloric acid = secreted by parietal cells to maintain the pH
- gastrin hormone = released by G cells to stimulate gastric acid and pepsinogen secretion
- pepsin = secreted by chief cells in the form of its precursor pepsinogen, once activated it breaks down proteins to peptides
What is the function of the stomach?
temporary reservoir for ingested food
reduce ingested solids to chyme by the action of acid and enzymatic digestion.
- chyme = semi-fluid mass of partially digested food that is expelled from the stomach into the duodenum
What is the small intestine? What are its properties?
small intestine = duodenum, jejunum, ileum
- main site of absorption
properties
- is the longest and most convoluted part = 4-5 m
- has a diameter of 25- 30 mm.
divided into:
duodenum = 200-300 mm in length, pH 5-6.5 , transit time > 5 mins
jejunum = 2 m in length, pH 6.9 , transit time > 1-2 hours
ileum = 3 m in length, pH 7.6 , transit time > 2-3 hours
the surface area of the small intestine increases by
- folds of Kerckring = inner circular folds
- villi = contain arteriole, venule and lymphatic vessels/lacteal
- microvilli = brush like structure that coves each villus
What are the barriers of oral absorption?
Gastrointestinal pH Luminal enzymes Food Physiological disorders Pre-systemic metabolism Mucus and unstirred water layer
How is gastrointestinal pH a barrier for oral absorption?
pH varies along the GIT
- starts with lower pH of 1-3.5 for the gastric fluid which increases to 3-7 after a meal and gets back to normal after 2-3 hours.
- intestinal pH is higher than gastric pH due to neutralisation with bicarbonate secreted by pancreas into small intestine
effect of pH on drugs
- can cause chemical instability = hydrolysis
- affect rate and extent of dissolution
- can affect absorption characteristics of the drug according to the ionisation status = must be unionised to pass the lipid bilayer
What are the luminal enzymes? How are luminal enzymes a barrier for oral absorption?
pepsin and protease, lipase, esterase, colonic bacteria secrete enzymes
pepsin and protease
- cause degradation to drugs which are protein in nature = nucleotides
lipase
- affect the release of drug from fat/oil containing dosage forms
ester drugs
- susceptible to hydrolysis by esterase enzymes in the lumen
colonic bacteria
- secretes some enzymes that could break drugs = sulfasalazine
How is food a barrier for oral absorption?
presence of food can also affect the rate and extent of absorption either directly or indirectly
effect
alteration of pH
- food acts as a buffer = increases the pH which would reduce the dissolution of weak basic drugs and increase it for acidic drugs.
cause stimulation of gastric secretions
- gastric secretions would degrade the drugs
= bile secretion cause by fatty foods forms complexes with neomycin and nystatin
competition for absorption.
increase viscosity of gastrointestinal contents
- result in reducing the dissolution rate.
increase blood flow to GIT and liver
- resulting in lower metabolism for drugs due to saturation of metabolising enzymes
= propranolol
How are physiological disorders a barrier for oral absorption?
GIT physiological disorders affect the absorption and hence the bioavailability of orally administrated drugs.
- local diseases can alter the gastric pH and hence affect the stability, dissolution and absorption of drugs
example
- patients with ulcerative colitis and Crohn’s disease have lower pH
- AIDS causes over secretion of gastrin and hence low pH
