Gastroretentive Drug Delivery Systems

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Oral is the most convenient and acceptable route for drug delivery. Conventional dosage forms have several disadvantages which were overcome by the development of several novel drug delivery systems. Gastroretentive drug delivery systems are one among such novel drug delivery systems. These are usually intended to deliver the active pharmaceutical ingredient specifically in the gastric region that is preferably in the stomach region. Based on the mechanism of retention these drug delivery systems further classified into hydrodynamically balanced systems, floating systems, expandable systems etc. The presentation mainly gives an idea of what the Gastroretentive drug delivery systems are? Their classification, the main mechanism by which retention is achieved in the class, evaluation tests for Gastroretentive drug delivery systems. The presentation includes –

 Introduction
 Definition
 Gastrointestinal dynamics
 Need for gastroretention
 Factors effecting gastroretention
 Types of gastroretention systems
 Evaluation of gastroretention systems
 Conclusion

Key words:
Gastroretention, hydrodynamically balanced, floating systems, swellable systems, effervescent systems, stomach, lag time, swelling index

Profile link page of the author: http://www.pharmainfo.net/shafichamp

Profile link page of the guide: http://www.pharmainfo.net/sudha

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Comments

Virag Shah's picture

Hello madam, your presentation is nice... But i am having some queries..... As you have told that gastrorentention can increase the bioavailabilty of drug. If we formulate a BCS class 3 drug which is having absorption only in upper intestine as a bioadhesive system....Can the bioavailability be increased ??? can you explain this in details.... Regards, Virag Shah http://www.pharmainfo.net/viragshah
Sudha Thamarapalli's picture

hello... BCS class III drugs are those with high solubility and low permeability. Absorption is the rate limiting step in them. In case of GRDDS the main aim is to retain the dosage form in thestomach for prolonged time periods. As these drug delivery systems cannot enhance the permeability of such drugs, their bioavailability cannot be enhanced. However, incorporation of permeation enhancers may improve thier bioavailability. eg: oleic acid, SLS etc. Ref: Mohd Yasir et al, Biopharmaceutical classification: an approach, International Journal of PharmaTech Research, vol 2 (3), 1681-1690 Regards, Sudha.T www.pharmainfo.net/sudha

Regards,

Sudha.T

Abhishek Rathi's picture

Dear Authors, Good efforts reflected through your presentation. I have a query that as you mentioned different approaches for this formulation, is there any marketed formulation available for these appraoches specifically for Magnetically controlled one? Regards

Abhishek Rathi

SS Md Shafi's picture

Thank you mr.Abhi.. yes there is a example for marketed formulation of magnetically controlled system e.i. available as "POLYOX" in the market. It is a water soluble and nonionic resin with good lubricating ,binding ,filmforming properties.

shafi ..

Sudha Thamarapalli's picture

Hello, These are some of the marketed products- 1. MADOPAR- Floating capsules 2. LIQUID GAVISCON- Effervescent floating lliquid alginate preparation 3. CONVIRON- Colloidal gel floating form 4. Hassan MOHAMMAD developed GASTRORETENTIVE DRUG DELIVERY SYSTEM COMPRISING AN EXTRUDED HYDRATABLE POLYMER. 5. GAVISCON ADVANCED TABLETS- Raft forming Ref: http://www.faqs.org/patents/app/20090324694#ixzz13fARZV3R http://www.ajpcr.com/Vol3Issue1/250.pdf

Regards,

Sudha.T

Sudha Thamarapalli's picture

hello, Research is still going on regarding magnetic systems. But some works were carried out in rabbits where bioadhesives granules containing ultrafine ferrite (g-Fe2O3). They guided them to the oesophagus with an external magnet (1700 G) for the initial 2 min and almost all the granules were retained in the region after 2 h. Fujimori et al. formulated a magnetic tablet containing 50% w/w ultra ferrite with hydroxypropylcellulose and cinnarizine. In beagle dogs, the tablet remained in the stomach for 8 h by the application of a magnetic field (1000 to 2600 G). Ref: Fujimori et al., November 16, 1995, Effect of magnetically controlled gastric residence of sustained release tablets on bioavailability of acetaminophen, International Journal of Pharmaceutics,119,1,47-55. Regards, SUDHA.T

Regards,

Sudha.T

Sirisha Pingali's picture

hello sudha and shafi your presentation is worth reading. Very well expressed. Does REFLUX tablets come under raft forming systems?? The common mechanism involved in gastroretentive systems is swelling. Am i right?? Are the limits for general tests of these gastroretentive delivery systems similar to normal tablets??

Sirisha Pingali

http://www.pharmainfo.net/sirisha

Viswanadha Institute of Pharmaceutical Sciences.

www.vnips.edu.in

Sudha Thamarapalli's picture

Hello sirisha, yes, reflux tablets are a type of raft forming tablets. And regarding the mechanism apart from swelling gastroretention is also achieved from effrvescence or bioadhesion or sinking. Regards, SUDHA.T

Regards,

Sudha.T

SS Md Shafi's picture

hi..... Along with general tests flowing lagtime test (should below 15sec-1 min) and swelling index tests have to be performed.

shafi ..

SS Md Shafi's picture

There is no common mechanism for all systems. these are not only swellable systems but also there are bioadhesive and floating systems..etc..

shafi ..

Pooja Chowdary's picture

on which basis Gastroretentive drugs are evaluated?

pooja

Pooja Chowdary's picture

can you mention some drugs which are unsuitable for gestroretentive drug delivery systems?

pooja

SS Md Shafi's picture

hi... The drugs which are unsuitable for the GRDDS are the first pass drugs , drugs which are not stable at acidic pH, ex:antibiotics.

shafi ..

Harsh bansal's picture

hello i want to ask u there r numbers of product which are degrade in stomach acid. i want to ask that if we use the same salt in syrup form what would be effect in that preparation? thank you

harsh bansal

Pooja Chowdary's picture

what are the future prospects of gastro retentive drug delivery system?

pooja

Arun Kumar Palle's picture

I think you have forgotten to explain the disadvantage of first pass metabolism? How this effect can be overcomed by this system?
Sudha Thamarapalli's picture

Hello Arun, first pass metabolism is a condition where concentration of a drug is greatly reduced before reaching the systemic circulation at liver and gut wall. In the stomach, the enzymes are mainly responsible for this effect. Therefore gastroretention of such drugs is not at all possible. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

The high meal content can increase gastric residence but at the same time it causes dilution of drug? How this point is useful for diabetic patients?
Arun Kumar Palle's picture

How this system is useful in treating other diseases except ulcer and colon disorders?
Sudha Thamarapalli's picture

hai, Along with treating such diseases.. this type of drug delivery system is useful for the drugs which have narrow absorptive index especially in the region of git. Eg. Gabapentin

Regards,

Sudha.T

Arun Kumar Palle's picture

Is this system useful in Delivering Levodopa
Sudha Thamarapalli's picture

Hello, Yes Arun... Levodopa has short half life and it undergoes absorption at proximal part of small intestine i.e, in the duodenum. So, gastroretention of this drug is definitely advantageous. Already it is available in the market under the brand name Madopar HBS(r). Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

Can you please explain me how the exactly floating mass is achieved? and retained up to how much period of time? Then how drug is released from it? What is the concentration of HPMC HEC can be used?
Sudha Thamarapalli's picture

hello arun, Your question:Can you please explain me how the exactly floating mass is achieved? there are different mechanisms of floating for different types of systems. i am explaining for the effervescent systems. Here a effervescent substance such as sodium bicarbonate will be present in the formulation. These carbonates or bicarbonates release carbondioxide as soon as they come in contact with the GI fluids. This gas gets entrapped in the polymer matrix present, as a result of which they will float. Your question:retained up to how much period of time? It depends upon our requirement. We can adjust the total floating time depending upon our requirement i.e., for how much time we want to control the drug release. Therefore it again depends on the daily dose of the drug which we choose. Your question:What is the concentration of HPMC HEC can be used? The concentration depends on a number of factors such as the viscosity grade of the polymer, total weight of tablet etc. It is not constant. In the final formulation we will choose the concentration where there is desired control in the drug release, desired lag time, desired total floating time, tablet integrity etc. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

How is gastric retention achieved with gas generating systems? How is the CO2 bubbles trapped in the matrix? If successfully trapped then what is the effect on physical and chemical stability? How can the CO2 sensitive drugs can be formulated by this type?
Sudha Thamarapalli's picture

hai... we have two types of controlled release tablets. 1. matrix type 2. reservoir type. matrix tablets are the one in which the polymer is mixed along with the drug and all the other ingredients. As the effervescent tablets reach the stomach some highly water soluble ingredients will get dissolved immediately and form cappilaries. water immediately enters the capillaries and convert carbonates and bicarbonates to carbondioxide. Due to the polymer matrix these gas bubbles remain entrapped. And in case of carbondioxide sensitive drugs, other modes of gastroretention can be done. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

What is the retention time of Raft forming system?
Sudha Thamarapalli's picture

hai, It is not a constant value. We have to optimize the retention time during formulation. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

Can you give me an example of marketed Raft forming system? How this exactly increases gastric retention? and how is it useful in treating PEPTIC ULCERS? How is the density difference achieved in order for Raft forming system? How is it stable from Gastric secretion's?
Sudha Thamarapalli's picture

hai, Liquid Gaviscon is an example for marketed raft forming type. These are more useful in treating gastroesophageal reflux than for peptic ulcers. These contain a gel-forming solution like sodium alginate solution containing carbonates or bicarbonates. When coming in contact with G.I fluids this solution swells and forms a viscous cohesive gel containing entrapped CO2 bubbles and produce a layer on the top of G.I fluids. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

In what dosage form these are ingested? How are density parameters achieved or the size of the system is not going to cross the orifice of the stomach? What are polymers which can be formulated for this system? How is the shrinkage and expandable mechanism achieved?
Sudha Thamarapalli's picture

hai, A dosage form in the stomach will withstand gastric transit if it is bigger than the pyloric sphincter. This principle is used in expandable and swellable systems. Expandable systems are based on mechanical properties where a dosage form which is small enough to be swallowed is prepared which on coming in contact with fluid unfolds and expands. Please check out the following link to see some pics of such systems. http://ctf.frm.uniroma1.it/didattica/att/1df8.2593.file.pdf Swellable systems are also retained because of their mechanical properties. The swelling is mainly because of the osmotic absorption of water into swellable layer. The dosage form is small enough to be swallowed, and swells in gastric liquids. The bulk enables gastric retention. Examples of swelling agents- differnt grades of HPMC, crosspovidone etc And after drug release these should be biodegraded. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

What is the retention time?
Sudha Thamarapalli's picture

hello, Normally gastroretentive systems are evaluated by- 1. lag time or floating time - it is the time required for the dosage form to float. 2. Total floating/ retention time - It is the total time for which the dosage form remains floating. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

What are the polymeric envelopes used? How is their evacuation takes place?
Sudha Thamarapalli's picture

hello, Polymeric envelope is nothing but here the polymer is coated unlike a matrix type. Evacuation should take place when their integrity is lost from time. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

What is the concentration of gel used? How is it going to evacuated? how Is this system going to release the drug? What are the age limits for its administration?
Sudha Thamarapalli's picture

Dear Arun, THE CONCENTRATION IS NOT A CONSTANT VALUE TO MENTION IT. It will be decided after performing various TRIAL & ERROR techniques. when coming to evacuation all the polymers we are using are biodegradable. as soon as the drug is released they should undergo degradation. These systems release the the drug from the pores formed through diffusion process. And as far as i know there is no age limit for ingestion of biodegradable hydrogels. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

It is best to go for bioadhesive systems apart from you mentioned? if not why?
Sudha Thamarapalli's picture

hello, We cannot say which way is best because it depends on the drug we choose. Regards, SUDHA.T

Regards,

Sudha.T

Arun Kumar Palle's picture

What is the strength of magnetic field to be applied? Is it not similar to BIOADHEsive method?
Sudha Thamarapalli's picture

DEAR ARUN, IT IS NOT AT ALL SIMILAR TO BIOADHESIVES. Research is still going on regarding magnetic systems. But some works were carried out in rabbits where bioadhesives granules containing ultrafine ferrite (g-Fe2O3). They guided them to the oesophagus with an external magnet (1700 G) for the initial 2 min and almost all the granules were retained in the region after 2 h. Fujimori et al. formulated a magnetic tablet containing 50% w/w ultra ferrite with hydroxypropylcellulose and cinnarizine. In beagle dogs, the tablet remained in the stomach for 8 h by the application of a magnetic field (1000 to 2600 G). Ref: Fujimori et al., November 16, 1995, Effect of magnetically controlled gastric residence of sustained release tablets on bioavailability of acetaminophen, International Journal of Pharmaceutics,119,1,47-55.

Regards,

Sudha.T

Arun Kumar Palle's picture

Can you shortly explain me how this system is better from other systems?
Sudha Thamarapalli's picture

hello, -The therapeutic window of many drugs is limited because of short half-life and narrow absorption window. once the dosage form passes the absorption window, the drug will be neither bioavailable nor effective. - localizes drugs at specific region of GIT such as stomach in the body. Regards, SUDHA.T

Regards,

Sudha.T

Pooja Chowdary's picture

What is the current scenario of this system?

pooja

Anil kumar appapurapu's picture

1. what is mean absorption time? 2. what are the evaluation test for GI retentive drug delivery systems? 3. pls explain the kinetics of drug delivery in terms of a. Higuchi release model b. Peppas release model.

anilkumar

Sudha Thamarapalli's picture

hai.. Evaluation tests include - 1. GENERAL TESTS: like Appearance, Hardness, Friability, Drug content, Weight variation, Uniformity of content, Dissolution time and Drug release. 2. Buoyancy lag time and the duration of buoyancy 3. Water uptake and weight gain Regards, SUDHA.T

Regards,

Sudha.T

Sudha Thamarapalli's picture

To analyze the mechanism of the drug release rate kinetics of the dosage form, the obtained data were fitted into zero-order, first order, Higuchi and Korsmeyer-Peppas release model. HIGUCHI- To study the Higuchi release kinetics, the release rate data were fitted to the following equation, F = k t1/2 Where 'k' is the Higuchi constant. In higuchi model, a plot of % drug release versus square root of time is linear. KORSMEYERS-PEPPAS - The release rate data were fitted to the following equation, Mt /M0 = K.tn Where, Mt /M0 is the fraction of drug released, 'K' is the release constant, 't' is the release time. 'n' is diffusion exponent, n-value overall diffusion mechanism 0.45 Fickian diffusion 0.450.89 super Case II transport

Regards,

Sudha.T

Anil kumar appapurapu's picture

good work 1. how can we measure the swelling index for these tablets? 2. how can we measure the entrapment efficiency ? 3. Explain the mechanism for increasing gastric residence time by this delivery? thank you

anilkumar

Sudha Thamarapalli's picture

Hai, The swelling behavior of dosage unit can be measured by studying its dimensional changes, weight gain or water uptake. The study of the tablet was done in using USP dissolution apparatus I. The medium used can be distilled water, 900ml rotated at 50 rpm at 37oC. After definite time intervals, the tablets (in basket) were with drawn, blotted to remove excess water and weighed. Water uptake (WU) is measured in terms of % weight gain as given by the equation below Wt - Wo WU = ------------------- X 100 Wo Where, Wt is the weight of the swollen tablet Wo is the initial weight of the tablet whereas coming to the increse in residence time, all the mentioned systems can be used. Regards, SUDHA.T

Regards,

Sudha.T

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