Colon-Specific Drug Delivery

Submitted by Gaurav Vadnerkar on Thu, 09/10/2009 - 11:53

The challenge of targeting drugs specifically to the colon has been embraced by scientists over the past two decades. Previously thought of as a Black Box, the colon is recently being explored as an increasingly important site for drug delivery. Research interest in the area of colonic drug delivery has been fuelled by the need to treat debilitating pathologies of the colon like amaebiosis, inflammatory bowel diseases and colon carcinoma, in a better way. Targeted drug delivery to colon would ensure direct treatment at the disease site, lower dosing and reduction in systemic side effects. Colon can also be utilized as a portal for the entry of drugs into the blood for systemic therapy. Drugs that are degraded and/or poorly absorbed in the upper gut may be preferentially absorbed from the colon because of the lower luminal and mucosal digestive enzymes and more residing time, as compared to small intestine. Colonic drug delivery may also be used as a means of achieving chronotherapy of asthma and arthritis that are sensitive to circadian rhythms.

To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper GIT and then be abruptly released into the proximal colon, which is considered the optimum site for delivery of drugs.

Potential candidates for colon-specific delivery are antimicrobials, immunosupressants, aminosalicylates, proteins and peptides. The various strategies for targeting orally administered drugs to the colon include prodrugs, coating with pH-sensitive polymers, timed release systems, exploitation of carriers that undergo colon- specific degradation or plant polysaccharides such as amylose, inulin, pectin and guar gum that remain unaffected by gastrointestinal enzymes, bioadhesive and osmotic controlled drug delivery systems.

My power point presentation deals with challenges, merits, demerits and future trends of colon-specific drug delivery in details.

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Comments

majumdarshiv's picture

majumdarshiv

Fri, 09/11/2009 - 06:50

Dear Gaurav,

While evaluating these drug-delivery system in-vitro, specially dissolution test, how one can mimic the in-vivo as colon contains some micr-flora that has role in dissolution of drug?

Regards
Shiv

My Team :
http://www.pharmainfo.net/blog/team-infinity

My Page :
http://www.pharmainfo.net/majumdarshiv/biography

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Sat, 09/12/2009 - 11:36

Dear Shiv,

Thanks for the comment and ur interest at the outset.

For in-vitro evaluation of these drug delivery system one can use simulated fluids like simulated intestinal fluid (composition given in USP XXIV)if the drug delivery system is not dependent on colonic micro-flora for releasing the drug.

In other case (i.e. when system is dependent on colonic micro-flora for releasing the drug) fecal and cecal contents of animal can be used and the system can be incubated with these contents under anaerobic conditions (to mimic environment in colon) and release can be studied.

I hope that my answer will clear ur doubt regarding in-vitro evaluation of colon-specific drug-delivery system.

If u'r still not satisfied with the answer or have any other query please feel free to ask me. I'll try to answer ur query to the best of my knowledge.

Warm Regards

Gaurav

amolsmalpani's picture

amolsmalpani

Sun, 09/13/2009 - 10:04

Dear Gaurav,
Is there any efflux transporters available in colon region, if yes, please explain their function regarding colon specific drug delivery?
Regards,
Amol

Amol S Malpani

Second prize Winners of Skills Test 2010

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 09/14/2009 - 07:06

Dear Amol,

Thanks for ur response

As far as ur question is concerned i would like to tell you that YES efflux transporters do exist in the colon but often efflux transporters and metabolic enzyme levels are lower in the colon (Ref: McConnell, Emma L.; Liu, Fang1; Basit, Abdul W., Journal of Drug Targeting, Volume 17, Number 5, June 2009 , pp. 335-363(29)).

I have pasted a link below plz follow this link to get more details about functions of efflux transporters for CSDD.

Expert Opinion on Drug Metabolism & Toxicology
July 2008, Vol. 4, No. 7, Pages 923-939 , DOI 10.1517/17425255.4.7.923

Regards

Gaurav

amolsmalpani's picture

amolsmalpani

Tue, 09/15/2009 - 14:16

Dear Gaurav,
Some factors affecting colon release like pH of GIT, quantity and quality of microflora,transit times of different segments of GI tract. These all vary in measurable amount in healthy and diseased condition. Is there any remedy for designing proper delivery in such conditions?
Regards,
Amol

Amol S Malpani

Second prize Winners of Skills Test 2010

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 09/21/2009 - 11:47

Dear Amol,

Thanks for the post

As rightly said by u various factors like pH of GIT, quantity and quality of microflora,transit times of different segments of GI tract vary in measurable amount in healthy and diseased conditions. The only way out is to evaluate the designed delivery system under these conditions that will give a better idea about its utility under such circumstances.

Delivery systems can also be specifically designed for these conditions taking into consideration the changes that are occurring in these diseases.

Regards

Gaurav

majumdarshiv's picture

majumdarshiv

Mon, 09/14/2009 - 04:48

Dear Gaurav,

Thanks for the reply.

As you mentioned fecal and cecal contents of animal, which animals are preffered in such cases? I observed some M-Pharm projects in which they used fecal and cecal contents of mice & rats.

Regards
Shiv

My Team :
http://www.pharmainfo.net/blog/team-infinity

My Page :
http://www.pharmainfo.net/majumdarshiv/biography

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 09/14/2009 - 06:36

Dear Shiv,

Its good to hear from u again.

As u've rightly said using fecal and cecal contents of rats and mice is the ideal most way of mimicking in-vivo environment for in-vitro release studies. The only thing that has to be kept in mind is during incubation one has to maintain anaerobic conditions (5% CO2) as seen in colon.

Regards

Gaurav

anuja raut's picture

anuja raut

Sun, 09/27/2009 - 11:26

What are the brand names for Multi matrix delivery systems? Are they available in India?

thanks

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Wed, 09/30/2009 - 10:49

Dear Anuja,

Thanks at the outset for ur query!

There are many Multi matrix delivery systems available in India and are available under Trade Mark MMX.

Like MMX Mesalazine for the treatment of IBD

Regards

Gaurav

Manickavasagam's picture

Manickavasagam

Tue, 09/29/2009 - 15:57

What are the factors to be considered before deciding the route of administration for colon specific drug delivery?

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Wed, 09/30/2009 - 10:47

Dear Manickam,

Thanks for ur query!

As u must've read in my presentation colon-specific drug delivery can be employed for drugs which:
1. show poor bio-availability from stomach and small intestine and/or have deleterious effect on gastric mucosa.
2. which are unstable or degraded in the upper GIT.
3. are required for the treatment of local diseases of colon like inflammatory bowel disease, ulcerative colitis, amoebiasis and colon cancer.

Regards

Gaurav

rujuta_mehendale's picture

rujuta_mehendale

Tue, 09/29/2009 - 16:46

Very good presentation!

The colon hoses a variety of enzymes like the sulfatase, hydrogenase and esterase etc. Can you tell me the effect of these enzymes on the therapeutic efficiency of the colon targetted drugs?

For example, if the drug is acted upon by the enzyme esterase, which is commonly found in the colon, and it gets esterified into a pharmacologically inactive metabolite, it may lead to undesirable consequences. what can be done to prevent this?

Thanks!

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Wed, 09/30/2009 - 10:43

Dear Rujuta,

Thank you very much at the outset for your compliment!

As you rightly said the colon has variety of enzymes like the sulfatases, hydrogenases and esterases. Here I would like to clarify you that the basic function of these enzymes is to cleave these bonds (if at all present in any drug candidate) and not synthesis of these bonds as for that synthase kind of enzymes 'll be needed.

Regards

Gaurav

ayushsinghal's picture

ayushsinghal

Fri, 10/02/2009 - 07:17

1)which are the available marketed products under this category?

2)Are there no side or toxic effects of the same?IF yes please mention the same.

thank you...

Ayush A. Singhal RPCP, CHANGA GUJARAT http://www.pharmainfo.net/ayushsinghal/biography
Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Sat, 10/03/2009 - 07:30

Thanks for the comments!

All the technology used for colon-targeted delivery is currently available in the market and u can find their brand names in my presentation.

No delivery system is free from side-effects and depending on the delivery system the side effect vary like for prodrugs side effects can be due to irrational or improper selection of carrier e.g. in case of sulfasalazine that uses sulfapyridine as carries have blood dyscrasias and hypersensitivity as side effects.

Regards

Gaurav

abherids86's picture

abherids86

Fri, 10/02/2009 - 07:56

Hi Gaurav,

Nice Presentation.
What is the working principle of colon targeting prodrugs?

Thank You.

ABHERI DAS SARMA
http://www.pharmainfo.net/abherids86

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Sat, 10/03/2009 - 07:24

Thanks for the comment!

Prodrugs are basically inactive molecules that release the active drug and carrier (Biologically active or inactive) through enzymatic activation and depending upon the type of prodrug synthesized the activating enzyme varies from azo reductase for azo conjugates to amidases and esterases for amide and ester prodrugs respectively.

Regards

gaurav

Khushbu Hasmukh Patel's picture

Khushbu Hasmukh...

Fri, 10/02/2009 - 14:45

nice presentation
Which are the marketed preparation under this drug delivery system
What are the benifit of tis drug delivery system?

K.H.Patel.
My profile link is
http://www.pharmainfo.net/khushbu-hasmukh-patel

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Sat, 10/03/2009 - 07:21

Thanks a lot for those encouraging words!

Various marketed preparations are available under these delivery systems and if u go through my presentation u can find their Trade mark names and benefits in it.

Regards

Gaurav

anis0019's picture

anis0019

Fri, 10/02/2009 - 14:53

Hi Gaurav,

thats a nice presentation
What is the kinetics of drug release from colon specific drug delivery device?

Thank You.

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Sat, 10/03/2009 - 07:19

Dear Anisur,

Thanks for those encouraging words!

As far as kinetics of these delivery systems is concerned it varies from one delivery system to other depending on the objective of its development.

Regards

Gaurav

kamala

Sat, 10/03/2009 - 14:44

Dear sir,
As we know in western countries the most common disease was ulcerative colitis .will the colon specific drug delivery be the most effective in treating this disease?If so, how?
THANKING YOU
REGARDS
KAMALA

kamala
Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 10/05/2009 - 04:55

The main objective of colonic drug delivery is to treat various local diseases of colon like CD and UC. Prodrug approach has been extensively explored for the treatment of UC by localized delivery of Drug at the site of action i.e. colon.

Regards

Gaurav

ganesh.nirma's picture

ganesh.nirma

Sun, 10/04/2009 - 12:14

hi,

Its a good presentation and good descriptive content.

I want to ask that what about the factors affecting the colon drug delievery like pharmaceutical and physiological factors??

can coating with microparticle can be done for better release?

regards
Ganesh.

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 10/05/2009 - 04:51

All Colonic drug delivery are designed taking various pharmaceutical and physiological factors into consideration. U can find a detail of this in my presentation.

ganesh.nirma's picture

ganesh.nirma

Sun, 10/04/2009 - 12:20

hi,

one more question?
are the marketed preparation are available in india?
can it be used in sustain release, time release from also??

regards
ganesh.

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 10/05/2009 - 04:53

Yes! All these formulations are available in India and can also be designed in sustained and time release format depending on the disease condition.

Regards

Gaurav

ankit's picture

ankit

Sun, 10/04/2009 - 15:15

dear Gaurav Vadnerkar ,
nice presentation.
please give me some idea about the evaluation parameters taken into consideration in invivo & invitro study of various systems & technique mention in your presentation.
what is a future perspective regarding this system..??
regard
ankit

http://www.pharmainfo.net/ankit

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 10/05/2009 - 04:48

The various evaluation parameters taken into consideration in invivo & invitro study are:
1. Stability in Upper GIT
2. Release profile of the system
3. Residence time in colon
4. Pharmacological parameters.

Future prospects in what sense????

Regards

Gaurav

Lakshmi's picture

Lakshmi

Sun, 10/04/2009 - 18:43

Dear Gaurav Vadnerkar,

Suppose if there is alteration in the pH of the colon due to systemic acidosis or alkalosis, Will there be effective drug release from pH dependant systems? If so what could be the possible remedy?

Gaurav Vadnerkar's picture

Gaurav Vadnerkar

Mon, 10/05/2009 - 04:45

Dear Laxmi,

Thanks for the comment!

Systemic acidosis or alkalosis hardly affects pH dependent colonic delivery.

Regards

kiran_mandlem's picture

kiran_mandlem

Tue, 10/13/2009 - 05:06

Is there any advantage of colon drug delivery apart from using in colon cancer.

Kiran
My Page Link : http://www.pharmainfo.net/kiranmandlem