GI 06 Flashcards
How many ways we can be able to treat the condition of GI tract?
2 ways
Oral and Rectal
Why do we need to think about drug formulation for treating GI disorders?
Transit time: Because the material will move through the intestine at different rates depends on their formulation like solid or liquid.
pH: because the stomach is more acidic where is the next part of the GI ph. reduce slowly.
Omeprazole is used to treat
Ulcer and GORD
Funded brand in NZ is
Omeprazole Activis. Omeprazole is Oral capsule form with gelatine capsule
With enteric coated granules.
What is MUPS ?
Its abbriviation is Multi Unit Pellet system.
This enteric coated granules system called MUPS
How omeprazole absorb and work ?
Omeprazole absorbs into our small intestine then systemically goes near the pumps into our stomach and it binds in a low acidic environment (prodrug) with the pump irreversibly and covalently. In our blood it stays inactive then comes near CRYPTS of gastric mucosa and than activate from the prodrug in the presence of low acidic environment.
Where proton pump inhibitor (Omeprazole) works?
Pump
Does omeprazole is Acid labile or Base labile ?
Acid labile because
In higher pH the degradation rate of omeprazole is lower.
In lower pH the degradation rate of omeprazole is higher.
Calculate the t90 for omeprazole degradation at pH 7.0 and 10.0 at 25 degree Celsius.
So remember if the drug degradation occur in a linear rate its first order rate e degradation.
Y axis is= rate of degradation in the graph. X is in different pH .
So Y= -0.69x+4.5
Remember to put, log k = - 0.69 pH + 4.5
Therefore, log k= -0.69x7+ 4.5
k= - 0.33 (If we take out the log)
k= 0.4677
k=0.47 (Now we got K)
T90 =0.105/k
T90=0.105/0.47
=0.22 days
Now calculate the t90 for Omeprazole at pH 10 at 25 degree Celsius
Need to do
How stable is omeprazole ?
By looking this table we can see that omeprazole is become precipitated in Low pH whereas in high pH or low acidic environment it has 100 percent effect.
How is omeprazole formulated ?
Tablet with enteric coated granules
Capsule filled with enteric coated granules.
What coating is required for a acid labile drug ?
Enteric coting because this coat will help to protect our acid labile drug.
What does the meaning of ‘Conventional’ mean ?
Immediate release
In which pH enteric coating breaks down ?
The enteric coating stay intact at low pH and release, break down at higher pH.
Why enteric cote?
Because it will maintain the formulation at low ph or High acidic environment.
And the enteric cote will protect our acid labile drug(omeprazole). SO it improves bioavailability.
Because our drug needs to go to small intestine which is the primary site for Omeprazole absorption or breaks.as the intestinal pH is higher and low acidic so drug will absorb or degrades or breaks a part.
All lime juice ph is around
2.something
Polymer used for enteric coating called:
Eudragid
Solubility of this polymers depends on pH.
In which pH PVAP (Polyvinyl acetate) become soluble?
is soluble at pH 5
In what pH the Shellac (polymer) become soluble ?
Is soluble in pH 7
Who might have problems of swallowing a tablet ?
Kids Parkinson's disease Radiotherapy in the neck area Kids Survivors of stroke
What if a patient can’t Swallow a omeprazole tablet ?
As pharmacist you might thing about other formulation type.like omeprazole capsule.
Or might think about Tube called Nasogastric tube by nose to stomach.
What is good about Nasogastric tube ?
Maintain stability of Omeprazole
Ensure correct dose
Volume need to be adjusted while administering.
To washing off the pellets what fluid we might use ?
lemon juice is better as they are low ph or high acidic.
Why sodium bi carbonate is used in omeprazole formulation ?
As suspending agent. Why is that because can easy to swallow.
The pH of sodium bicarbonate is
8.3
Site specific targeted delivery or Azoreductase activity?
In our colon several hundred species of bacteria stay and the unique thing is that they produce variety of enzymes so we can use their enzyme in the colon and formulate. And if we have inflammation in that particular region than we can utilize those bacterial enzyme as mechanism to target and only we have our drug acting at that site. Those enzymes that degrade azodyes.Azo reductase activity enzyme secretion is higher in Caecum colon and Rectum.
For example: Sulphasalazine designed as inactive derivative of a drug that requires enzymatic transformation in vivo to release (sulfapyridine) and 5-aminosalacyclic acid (5-ASA)cleave the azo bond. the active moiety topically and locally into the colon.
Where 5- aminoalicyclic acid absorb ?
Rapidly absorb in jejunum.
How many variety of bacteria stays in our colon ?
Several hundreds i.e. Enterococcus faecalis
What Is the chemical name of sulphasalazine =>
(sulfapyridine) and 5-aminosalacyclic acid (5-ASA) joined by an azo bond.
Who is the first and second generation of 5 ASA (1st gen Sulphasalazine) (Next gen: Pentasa) and why
Because of 1st gen has some side effects.
Why Pantasa has liquid enemas or suppository ?
Local treatment. Only for distal colon but not good to apply deeper.
What is Asacol oral tablet
Whole tablet is enteric coated delayed release.
Eudragid (Methacrylic co-polymer) dissolved at pH>7 in Ileum and colon
Aminosalicylate (Sulfasalazine) for IBD use
Salphasalazine is a pro drug and it active drug is 5 aminos alicyclic acid (5ASA) which has anti inflammatory component, so sulfasalazine will not absorb its 100 percent and reaches in the colon the enzyme of bacteria will then cleave the N=N bond of the drug and separate 5ASA from Sulphapyridine.
Note: If you look 5ASA drug on of its own it is well absorbed in the duodenum. So if you do not make this drug as prodrug or add a sulphapyridine group on there it will not reach to colon.
Pentasa is used for
UC and CD
Time dependent release
Prolong release of microgranules with cellulose coating which is semi permeable.
Release continuously over the GIT
Release at all pH condition.
What is the patient advice for pentasa tablet ?
Tablet and Granules formulation but do not crash or chew as they are controll release
Oral formulation mesalazine is SR so advice would be ?
microgranules so the advice is do not chew or crush the granules.
Rectal formulation Pantasa also have formulation Liquid enema for
Local treatment. Only for distal colon not good to apply deeper. So shake well before use.
Pantasa: It also has suppository formulation but it only give
Local effect so use for mild condition.
Asacol oral tablet
Whole tablet is enteric coated and delayed release.
Eudragid (Methacrylic co-polymer) dissolved at above pH>7 in Ileum and colon
It also have rectal preparation Suppository.
Which strategies is the best for formulating prodrug ?
Ph Dependent strategies.
