Colon Targeted DDS Flashcards
What are the Advantages of CTDDS over
conventional drug delivery? (4)
Reduce the adverse effects in the treatment of colonic diseases (ulcerative colitis, colorectal cancer, crohn’s disease)
Produce the ‘friendlier’ environment for peptides and proteins as compared to upper gastrointestinal tract
Prevent the gastric irritation produced by oral administration of NSAIDS.
Delayed release of drugs to treat angina, asthma and rheumatoid arthritis
What are the Limitations of CTDDS
the fluid content in the colon is lower and more viscous than in upper GIT, which is the limiting factor for poorly soluble drugs.
Lower surface area and relative tightness of the tight junctions in the colon can restrict drug transport across the mucosa into the systemic circulation
what can we use to facilitate absorption of drug from colon?
Permeation enhancers
What drugs are Candidates for CTDDS
Drugs showing poor absorption from stomach/ intestine including peptides
Drugs use in treatment of IBD amobiasis colon cancer…
Drug should be compatible with carrier molecule (prodrug)
Should be stable at alkaline pH of GIT
Do I include permeation enhancer iza ana bede local action?
NO
Approaches for colon targeting (6)
- Conjugated prodrug
- Probiotic approach
- Coating with pH sensitive polymer
- pH sensitive hydrogel
- Time dependent drug delivery
- Pressure controlled drug delivery
1) Conjugated Prodrug
What are the types of conjugation
Azo bond
Glycoside
Glucuronide
What is an Azo bond conjugation
Azo bond is stable in the upper GIT
Cleaved in the colon by azo-reductase produced by microflora
e.g. Sulfasalazine
What is a Glycoside Conjugated prodrug
Glycosides are used as carriers for delivering drug to colon
e.g. dexamethasone-21-b-glucoside and prednisolone-21-B-glucoside
Glucuronide Conjugated prodrug
Specifically cleaved by B-Glucuronidases on the colon
i.e. glucuronide conjugation of narcotic analogs
Naxolone and nalmefene used in the treatment of constipation caused by opiate
2) Probiotic Approach
What are its components
Three components are desirable:
Probiotic strain
Microbially digestible carrier
Triggering temperature
What are Probiotic strains
Inactive microflora like bifidobacterium and lactobacillus
At body temp these strains get active and start digesting the carrier so the drug is released
3) Coating with pH sensitive polymer Approach
E.g. of ph dependent polymer
Emtan starts to release drug
Coating the tablet with pH dependent polymer
e.g. Eudragit S and L
The polymer remains intact in stomach bur start releasing small amounts at the distal part of s.intestine
As it enters the colon, the entire coat is dissolved and drug is released
The difference between Eudragit S and L
L ph>6 (aLkaline)
S ph<6
What is the major limitation of pH sensitive polymer (2)
It is contorlled by polymer coat thickness
Premature release can occur
4) pH sensitive Hydrogel
Acidic groups and basic groups
pH sensitive polymers contain acidic groups mtl Carboxylic acid and sulfonic acid or basic grp such as Ammonium salt that can either accept or donate proton, depending on the pH
E.g. of pH sensitive hydrogel polymer
Polyacrylic acid will become ionized at high pH leading to swelling of hydrogel and drug is released
Why does the Hydrogel swell>
Due to repelling of two charges
Are polyanions hydrogel bikaffo la7alon aw lezim a3ml shi?
Polyanions should be be crosslinked with azo aromatic crosslinkers
5) Time dependent Colon DD
It is based on what?
Lag time addesh?
It is based on the principle of delaying the time of drug release until it reaches the colon
A lag time of 5 hours is usually considered enough
Pulsatile release formulation
Pulsatile release system are formulated to undergo a lag time of predetermined span of time of no release, followed by a rapid and complete release of loaded drug
What is he Disadvantage of Time dependent CDDS
Depends on gastric emptying
6) Pressure controlled DDS
Capsules are prepared using shu?
How is drug released
Lag time?
El capsule is made of what? wl drug is in what form
Capsules are prepared using ethyl cellulose that is insoluble in water
Drug release occurs following the polymer breakdown due to lumen pressure of colon
Ethyl cellulose unit capsule, the drug is in liquid form
Lag time 3-5 hrs in relation to drug absorption
Examples CTDDS combining
different approaches
- ETP tablets
- Pulsincap
- Portsystem
- CODESTM
Enteric coated time-release press coated tablets
(Time + pH)
After gastric emptying, the enteric coat (Eudragit L rapidly dissolves in intestine) rapidly dissolves in intestinal fluid and erode the press coated polymer HPC layer
After erosin reaches the core tablet, Drug is release rapidly
How is lag phase of ETP tablet controlled?
The duration of lag phase is controlled by weight or composition of HPC layer
2) Pulsincap
e.g. of water soluble cap?
Acid insoluble coating?
Where is drug released?
A capsule consists of non disintegrating body part and water soluble cap and hydrogel plug
Water soluble cap e.g. Gelatin
Acid insoluble coating e.g. Enteric coat
The cap and the cap coating are dissolved in intestinal fluid
Hydrogel plug expands in intestine (swells)
Drug is released in colon
3) Portsystem
What does it consist of?
After the cap dissolves wl drug is released, shu byaaml el semipermeable membrane
Consists of a hard gelatin capsule that is coated with cellulosic semi permeable membrane (allows water in)
Inside the capsule an insoluble plug and osmotic active agent
1-Cap dissolved off,
2-IR or MR dose is released,
3-semipermeable membrane allows water in,
4-plug is expelled over time due to pressure,
pulse or sustained release of drug
4) Novel CTDDS
Combination of shu?
Avoids what problem?
Developed using what
System consists of
(Time + Microbiota)
Avoids pH or time problem
Is a combined approach of pH dependent and microbiota
Developed using lactulose that acts as a trigger for site specific drug release in colon
System consists of tablet core with lactulose
Coated by acid soluble material Eudragit E
Overcoated by enteric material Eudragit L
What does the Novel System consist of?
Tablet core containing lactulose
Core is coated with acid soluble material i.e. Eudragit E
Overcoated with enteric material Eudragit L
How is the tablet of Novel dissolved in body?
Enteric coating is dissolved in stomach
Acid soluble polymer Allows fluid in in small intestine
In colon, Lactulose is broken down by microbiota using galactosidase to produce lactic acid which provides and acidic environment and then drug is released
