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Abstract

In the current days, gastro retentive drug delivery systems (GRDDS) receive the great attention because they increase the performance of controlled release dosage forms, which can take orally. It is a widely employed technique to retain the dosage form in the stomach for a long period by releasing the drug slowly. These systems improved the patient compliance, which increases the therapeutic index of drugs. Various physiological barriers associated with the gastro retentive drug delivery systems such as short gastric retentive time, variation in gastric emptying time that can reduced by this technique. To formulate GRDDS various approaches like floating drug delivery systems, non-effervescent drug delivery systems, high density drug delivery systems, bioadhesive systems, magnetic systems, expandable systems etc.,. The present review mainly focuses on the requirements for formulating the GRDDS, various approaches involved in formulation and factors affecting gastric residence time.

Keywords

Gastro retentive drug delivery system (GRDDS) and Physiological barriers.

Introduction

Despite significant advancements in drug delivery, technology oral route is the most preferred route of administration for various active ingredients due to case administration, low cost drug, patient compliance, flexibility design of formulation1,2. Orally administered conventional dosage forms do not have proper controlled over drug release and lead to high fluctuations in plasma drug concentration3. However many drugs absorbed from specific sites and they require release at the particular site for better absorption. So the controlled release drug delivery systems has formulated to release the specific amount of the drug at particular site4. Controlled release drug delivery system widely employed due to various advantages like enhanced therapeutic action with in case in the duration of drug release and improves the bioavailability.  Gastro retentive drug delivery system are one of the type of controlled release drug delivery systems they can retain in the gastro intestinal region for a long  period of time and altering the gastric emptying time and motility pattern of GIT5.GRDDS are feasible for drugs that having low absorption in the lower part of GIT. Unstable, and poorly soluble at alkaline pH and the drugs having shorter half-life6,7.Various formulation related factors such as polymer types (non-cationic, anionic) polymer, composition, viscosity, molecular weight of polymer and drug solubility can effect the quality of the gastro  retentive dosage form8. The stomach is a J-shaped enlargement of the GI tract directly inferior to the diaphragm in the abdomen. The stomach connects the oesophagus to the duodenum, the first part  of the small intestine.

 ANATOMY OF THE STOMACH

The stomach has four main regions: the cardia, fundus, body and pyloric part. The cardiac surrounds the superior opening of the stomach. The rounded portion superior to and to the left of the cardia is the fundus. Inferior to the fundus is the large central portion of the stomach, the body. The pyloric part is divisible into three regions. The first region, the pyloric antrum, connects to the body of the stomach.  The second region, the pyloric canal, leads to the third region, the pylorus, which in turn connects to the duodenum. When the stomach is empty, the mucosa lies in large folds, or rugae, that can be seen with the unaided eye. The pylorus communicates with the duodenum of the small intestine via a smooth muscle sphincter called the pyloric sphincter. The concave medial border of the stomach is lesser curvature; the convex lateral border is greater curvature9 (Fig. 1: Anatomy of stomach).

FUNCTIONS OF STOMACH

The functions of the stomach include the following10

  1. Temporary storage allowing time for the digestive enzymes, pepsins, to act 
  2. Chemical digestion –pepsins break proteins into polypeptides.
  3. Mechanical breakdown- the three smooth muscle layers enable the stomach to act as a churn, gastric juice has added and the contents are liquified to chime. Gastric motility and secretion has increased by parasympathetic nerve stimulation.
  4. Limits absorption- water, alcohol and some lipid soluble drugs.
  5. Non-specific defence against microbes- provided by hydrolytic acid in gastric juice. Vomiting may occur in response to ingestion of gastric irritants, e.g. microbes or chemicals.
  6. Preparation of iron for absorption- the acid environment of the stomach solubilises iron salts, essential for iron absorption in the small intestine. 
  7. Production and secretion of intrinsic factor needed for absorption of vitamin B12 in the terminal ileum.
  8. Regulation of the passage of gastric contents into the duodenum. When the chyme is sufficiently acidified and liquefied, the pylorus forces small jets of gastric contents through the pyloric sphincter in the duodenum. The sphincter is normally closed, preventing, backflow of chime into the stomach.

 ADVANTAGES OF GRDS

  • The advantages11 regarding gastro retentive drug delivery system includes
  • It has been using in the treatment of peptic ulcer disease.
  • Commonly used for drug having narrow therapeutic index. To minimize the dosing frequency.
  • Improved bioavailability of drugs.
  • Used for drugs which are normally unstable in intestinal fluids.
  • Used to provide sustained delivery for the drugs used for maintaining maximum therapeutic drug concentration within the therapeutic withdraw.

 DISADVANTAGES OF GRDDS

  1. Although there are advantages, this also having disadvantages12,13. They are
  2. Drugs that are unstable in high acidic environment, very low solubility in acid environment causes irritation to gastric mucosa and cannot formulated as GRDDS.
  3. FDDS                                 (Floating       Drug    Delivery
  4. Systems) require high level of fluid in stomach for floating and working more efficiently. So more water intake has needed with such dosage form.

 FACTORS AFFECTING GRDDS

  1. Density

The density of the dosage form should be less than that of the gastric contents (1.004g/ml).

 2. Size

Dosage form having diameter of more than 7.5mm have more gastric residence time than that of 9.9mm diameter dosage form14.

  1. Shape of the dosage form

A diameter resided in the stomach for a longer period than other devices of similar size. The single or multiple unit formulation –multiple unit formulation show a greater predictable release profile and insignificant impairing of the performance due to failure of the units with different release profile or containing incompatible substances and permit larger margin of safety against dosage form failure compared with single unit dosage form.

 4. Fed or unfed state

Under fasting conditions, the GI motility has characterized by periods of strong motor activity that occurs every 1.5-2 hrs. The MMC (Migrating Motor Complex) sweeps undigested material form the stomach and if the timing of the formulation coincides with that of MMC, the GRT of the unit can be very short, however in fast state MMC is delayed and GRT is longer15.

 5. Nature of meal

Feeding of indigestible polymers or fatty acids can change the motility pattern of the stomach to a fed state, thus decreasing gastric emptying, rate and prolonging drug release.

 6. Caloric content

GRT can increased by 4-10 hours with a meal that is high in protein and fat.

 7. Frequency the meal

Feeding increase over 400 min when successive meals given are compared with the single meal due to low frequency of MMC16,17.

 8. Gender

Mean ambulatory GRT in male (3,4hrs) is less compared with the age and race matched female counterparts (4,6hrs) regardless of height, weight and body surface18.

 9. Age

People with age more than 70 have a significant longer GRT.

 10. Concomitant drug administration

Anti-cholinergic like atropine and propantheline, opiates like codeine can prolong GRT19.

 REQUIREMENTS FOR GASTRO RETENTIVE FORMULATION 

The requirements for formulating a GRDS, it include11

  1. Drugs that act locally in stomach (antacids and drugs for H. Pyloric viz., Misoprostol)
  2. Drugs those are primarily absorbed in the stomach (Amoxicillin)
  3. Drugs that is poorly soluble at intestinal fluids (Furosemide, Diazepam,
  4. Verapamil)
  5. Drugs which show a narrow window
  6. (Cyclosporine, Methotrexate, Levodopa)
  7. Drugs that are absorbed rapidly in the GI tract (Metronidazole, Tetracycline)
  8. Drugs that usually degrade in the colon (Ranitidine, Metformin HCl)
  9. Drugs that disorganize normal colonic microbes (Antibiotics against  Helicobacter pylori)

 COMMONLY USED DRUG IN FORMULATION OF GRDDS

The drugs, which satisfies the above requirements, can only formulated as gastro retentive drug delivery systems. Some of the examples of drugs has discussed in Table 1 and commercially available marketed products has discussed in Table 2 respectively20, 21.

APPROACHES FOR GASTRO RETENTIVE DRUG DELIVERY SYSTEM

There are various approaches for formulating the gastro retentive drug delivery systems. Some of the methods has depicted in Figure 2.

 1. Non-floating drug delivery systems

 a. High density (sinking) drug delivery system

The density of the formulation exceeds the density of the normal gastric content. The materials increase the density up to 1.5-2.4 gm/cm3. Depending on the density, the GI transit time of pellets can be extended from an average of 5.8-24 hours. But the effectiveness of this system in human beings was not observed and no formulation has been marketed22.

 b. Bioadhesive  or  mucoadhesive drug delivery system

The gastric retention time has extended by adhering the bioadhesive system for gastric mucous membrane.The adherence of the delivery system to the gastric wall increases residence time thereby improving bioavailability. The chemicals used for the mucoadhesion purpose include polycarbophil, carbopol, lecithin, chitosan, carboxy methylcellulose, gliadin etc.,23. Novel adhesive material derived from fimbrae of bacteria or its synthetic analogues have also been tried for the attachment to the gut. However, the gastric mucoadhesive force does not tend to be strong enough to resist the propulsion force of the stomach wall. The continuous production of mucus and dilution of the gastric content is another limitation for such type of system. Many investigators have tried out a synergestic approach between floating and bioadhesion system (Fig. 3: Mucoadhesive drug delivery system).

c. Magnetic system

In this system, the dosage form contains a small magnet and another magnet is placed on the abdomen over the position of the stomach. The external magnet should be placed with a degree of precision which may decrease the patient compliance.

d. Expandable System

These systems are capable of expanding and retain in the stomach for longer periods. These are usually formulated as a capsule containing dosage form folded and compact form. After being exposed to stomach environment, capsule shell disintegrates and dosage form expands preventing its exit through the stomach. By using a suitable polymer, sustained and controlled drug delivery can be achieved.

 Floating Drug Delivery System

a.  Effervescent System

These systems was further classified into

  1. Gas generating System

The main mechanism is involved in this system is the production of CO2 gas due to reaction between sodium bicarbonate, citric acid and tartaric acid. The gas produced results in the reduction of density of the system, thereby making it float on the gastric fluids. Salts and citric/tartaric acid release CO2, which entrapped in the jellified hydrocolloid layer of the system which decrease its specific gravity and making it float over chime24. The system consist of a sustain release pill as seed surrounded by double layer. The inner layer is an effervescent layer containing sodium bi carbonate and tartaric acid. The outer layer is of a swellable membrane layer containing PVA shellac. (Fig. 4: Effervescent drug delivery system)

  1. Volatile liquid containing system

These have an inflatable chamber which contains a liquid e.g. ether, cyclopentane, that gasify at body temperature to cause the inflation of the chamber in the stomach. These systems osmotically control floating system containing a hollow definable unit. These are two chambers in the system first contain the drug and the second chamber containing the volatile system.

These systems has again classified into following

Intra gastric floating gastrointestinal drug delivery system

This system contains a floatation chamber which contains vacuum or an inert, harmless gas and a micro porous compartment enclosing drug reservoir.

Inflatable gastrointestinal drug delivery system These systems possess inflatable chamber containing liquid ether which gasifiers at body temperature to inflate the stomach. Inflatable chamber contains bio erodible polymer filament (e.g Copolymer of poly vinyl alcohol and poly ethylene) that gradually dissolves in gastric fluid and finally cause an inflatable chamber to release gas and collapse.

Intra-gastric osmotically controlled drug delivery system

It is composed of osmotic pressure controlled drug delivery device and an inflatable floating capsule.in the stomach, inflatable capsule disintegrates and release the osmotically controlled drug delivery system which contains two components: drug reservoir compartment and osmotically active compartment. Superporous hydrogels are an excellent example, working on this approach. The dosage form swells significantly to several times of original volume upon contact with gastric fluid, the gastric contraction pushes the dosage form to the pylorus but due to the larger size of the dosage form , the contractions slips over the surface of the system, due to which the dosage form pushes back into the stomach.

 b. Non-effervescent systems

Non-effervescent system can be further divided in to hydro dynamically balanced system, Microbaloons, alginate beads and microporous compartment25. 

  1. Hydrodynamically balanced system

It is a formulation of a drug with gel forming hydrocolloids meant to remain buoyant in the stomach contents .Drug Delivery Systems have a bulk density lower than gastric fluids and thus remain buoyant in the stomach for a prolonged period of time, without affecting the gastric emptying rate. While the system is floating on the gastric contents, the drug is released slowly at a desired rate from the system. After the release slowly at a desired rate from the system. After the release of the drug, the residual system is emptified from the stomach. The results in an increase in the GRT and a better control of fluctuations in the plasma drug concentrations.

  1. Micro balloons

Micro balloons   (Hollow microsphere) are in the strict sense, empty particles of spherical shape without core. These microspheres are characteristically free flowing powders comprising of proteins or synthetic polymers, ideally having a size less than 200 micrometres. Micro balloons loaded with drug in their outer polymer shell are prepared by a novel methods such as solvent evaporation to create a hollow inner core. the drug and an enteric acrylic polymer mixture are dissolved in ethanol /dichloromethane solution and it is poured into an agitated solution of Poly Vinyl Alcohol (PVA) that as thermally controlled at 40 c. After the formation of stable emulsion, the organic solvent is evaporated from the emulsion by increasing the temperature under pressure or by continuous stirring. The gas phase is generated in the droplet of dispersed polymer by the evaporation of dichloromethane and thus formed the hollow internal cavity in the microsphere of the polymer with drugs.

  1. Microporous compartment

In this system, drug reservoir is encapsulated inside a microporous compartment having pores along its top and bottom walls. The floatation chamber containing entrapped air causes the delivery system to float over the gastric fluid enters through the aperture ,dissolves the drug and carries the dissolved drug in the stomach and proximal part of the small intestine for absorption.

  1. Alginate beads

Freeze dried calcium alginates have been used to develop multi unit floating dosage forms26. By dropping sodium alginate solution into aqueous solution of calcium chloride spherical beads of about 2.5 mm diameter can be prepared. These beads are separated and air dried. This results in the formation of aporous system which remains buoyant in the stomach. 

 EVALUATION

  1. Floating lag time (FLT), Total floating time (TFT) floating strength

For low-density system, raft-forming system  The test was carried out in a simulated fluid (SGF) at 370C. The time between introduction of dosage form and its buoyancy on the SGF (FLT) and the time during which the dosage form remains buoyant (TFT) were measured. The floating strength is measured using specifically designed basket holder connected with analytical balance. The reduction of weight on the analytical balance over time determines the floating  strength27,28.

2. Swelling studies For super porous hydrogel system, expandable system.

The test is carried out by placing the weighed amount of dosage form into the swelling medium (0.01N HCl) and weight, diameter, and length of swollen samples are measured at predetermined time point29,30.

 3. Viscosity and rheology

For  raft-forming  and  mucoadhesion systems.

Viscosity of polymer affects the consistency of the dosage form upon contact ith the gastriv fluid, Brookfield/Ostwald’s viscometer and texture analyzer are commonly used31.

 

  1. In vitro unfolding study For expandable system.

The test is carried out by placing the folded dosage form into the dissolution medium and examining its unfolding behaviour in different  time interval32.

  1. Particle size, ion exchange capacity, moisture content

For ion-exchange resin system.  Particle size analysis has carried out using a sieve shaker; laser diffraction and coulter counter analyser. The ion exchange capacity depends upon the functional group available for cross-linking. Moisture content can be measured with Karl

Fischer33,34. 

6. General parameters

a. In vitro drug release

The test is carried out in SGF at a predefined time interval (generally 012hrs)using USP type-II apparatus at 50 RPM and maintained at 370C35, 36.

b. Gel strength 

The high gel strength is desirable for better mechanical integrity37. 

c. Drug – Excipient interaction study

It can studied by using FT-IR spectroscopy, differential scanning calorimeter and high performance liquid chromatography38.

 CONCLUSION

Based on the recent advancements it has concluded that gastro retentive drug delivery system is a promising approach for the drugs having poor bioavailability prior to their absorption is restricted particularly in upper gastro intestinal tract there by maximising their absorption and enhancing the bioavailability. Due to their maximum retention in gastric region, these formulations has majorly used in treatment of gastro intestinal diseases like gastritis and peptic ulcer. Commercially it is emerging slowly as an important novel drug  delivery system with numerous potential  benefits.

REFERENCES

  1. Chawla G, Gupta P, Koradia V and Bansal AK.  Gastroretension:  A means to address regional variability in intestinal drug absorption. Pharmaceutical Technology.  2003;27:50-68.
  2. Garg Re and Gupta GD.  Progress in controlled gastro retentive delivery systems. Topical Journal of Pharmaceutical Research.  2008;7(3):1055-1066.  
  3. Yadav M, Sharma P, Chaudhary V and Srivastava B. Gastro retentive drug delivery system: a promising approach. Indo   American Journal of Pharmaceutical Research.  2016;6(4):5225-5235.  
  4. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC and Falson Fir. Gastro retentive dosage  forms:  Overview  and  special  case  of Helicobacter pylori. J  Control  Release.  2006;111( 1-2):1 -18.
  5. Patil JM, Hirlekar RS, Gide PS and Kadam VJ.  Trends in floating drug delivery systems.  Journal of Scientific and Industrial Research.  2006;65(1):11-21.
  6. Fujimori J, Machida Y, Tanaka S and Nagai T.  Effect  of  magnetically  controlled  gastric  residence  of  sustained  release  tablets  on  bioavailability  of  acetaminophen. International Journal of Pharmaceutics. 1995;119: 47-55.
  7. Klausner  EA, Lavy  E,  Friedman  M and Hoffmann  A. Expandable gastroretentive dosage forms. Journal of Controlled drug Release.  2003;90:143-162.
  8. Thapa  P and  Jeong  S.  effects of formulation   and  process  variables  on   gastroretentive  floating  tablets  with  a  high- dose  soluble drug  and  experimental  design  approach. Pharmaceutics. 2018;10:1-25.
  9. Gerard J Tortora and Bryan Derrickson. The digestive system: Stomach- Anatomy of the stomach. Anatomy and Physiology. Edited by Wiley. 2015; Indian Edition: 808.
  10. Anne Waugh and Allison Grant. The digestive system: Stomach-Functions of stomach. Ross ans Wilson anatomy and physiology in health and illness. Edited by Elsiver Publications. 2014; 12th Edition: 301.
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  12. Vyas SP. Controlled drug delivery: Concept and Advances. Vallabh Prakashan. 2006;196-217.
  13. Joseph R.  Controlled drug delivery fundamentals and application. Revised and Expanded Marcell. Dekker Inc. 2nd edition.  New York, 2009.
  14. Khosla R and Davis SS.  The effect of tablet size on the gastric emptying of non-disintegrating tablets.  International Journal of Pharmaceutics. 1990;69:R9- R11.
  15. Deshpandae AA, Rhodes CT, Shah NH and Malick AW. Controlled- release drug delivery systems for prolonged gastric residence. An overview.  Drug delivery Indian Pharmaceutics, 1996;22:531-539.
  16. Abrahamsson  B,  Alpsten  M, Hugosson  M, Jonsson  UE, Sundgren M,  Svenheden  A and Tolli  J.
  17. Absorption,  gastrointestinal  transit, and  tablet  erosin  of felodipine  extended  release  (ER) tablets.  Pharmaceutical Research.1993;10:709.  Oth M, Franz M, Timmermans J and Moes AJ. The bilayer floating capsule:  A Stomach directed drug delivery system         for     misoprostol.  Pharmaceutical research.1992;9:298.
  18. Hermansson   G and Sivertsson R.  Gender- related difference s in gastric emptying rate of solid meals, Digestive Diseases and sciences.  1996;41(10):1994-1998.
  19. Kaus LC, Fell JT, Sharma H and Taylor DC. Gastric emptying and   intestinal transit of non-disintegrating capsules- the influence of metaclopramide.  International Journal of pharmaceutics.1984;22(1):99-103.
  20. Arrora S, Ali J, Khar RK and  Baboota  S.   Floating drug delivery system: A review. AAPSE Pharma Science Technology. 2005;6(3):372-390.
  21. Chawla G, Gupta P and Bansal AK. Gastroretentive drug delivery system. In Jain NK. Editor.  Progress in Controlled and novel drug delivery system CBS Publication and Distributors. New Delhi. 2004;76-97.
  22. Clarke GM, Newton JM and Short MD.Gastrointestinal transit of pellets of differing size and density. International journal pharmaceutics. 1993;100(13):81-92.
  23. Moes AJ. Gastric retention system for oral drug delivery. Business briefing. Pharmatech. 2003;157-159.
  24. Misra SK. Gastrointestinal targetting drug delivery system: A Review. Journal of Pharmacy Research. 2011;4(8):2751- 2754.
  25. Rao  BP, Kottan   NA,  Snehith  VH and  Ramesh  C. Development of  gastroretentive  drug  delivery  system  of  Cephalexin  by  using  factorial  design.  ARE Pharmaceutical. 2009;50: 8.
  26. Sheth PR and Tossounian J. The hydrodyanamically balanced   system. A novel drug   delivery system for oral use.  Drug delivery Indian Pharmaceutics. 2010;3(1):819-833.
  27. Prajapati   VD, Jani GK, Khutliwala TA and Zala BS. Raft forming system - An upcoming approach of gastroretentive drug delivery system. Journal of Control Release. 2013;168: 151-165.
  28. Prinderre P, Sauzet C and Fuxen C.  Advances in Gastro-retentive drug- delivery systems. Expert Opin. Drug delivery. 2011;8:1189-1203.
  29. Chen YC, Ho HO, Lee TY and Sheu MT.  Physical Characterization and sustained release profiling   of gastroretentive drug delivery systems with improved floating and swelling capabilities. International Journal of pharmaceutics. 2013;441:162-169.
  30. Chen J, Blevins WE, Park H and Park K. Gastric retention properties of superporous hydrogel composities. Journal of Control release. 2000;64:39-51.
  31. Kashyap  N, Viswanad  B,  Sharma   G, Bhardwaj  V, Ramarao P and Kumar  MR.  Design and evaluation of biodegradable, biosensitive in situation gelling system for pulsatile delivery of insulin. Biomaterials. 2007;28: 20512060.
  32. Verma S, Nagpal K, Singh S and Mishra D. Unfolding type gastroretentive film of cinnarzine based on ethyl cellulose and hydroxypropyl methylcellulose. Int J Biol Macromol. 2014;64:  347-352.
  33. Anand V, Kandarapu R and Garg S. Ion exchange resins: carrying drug delivary forward. Drug discov. Today. 2001;6:905-914.
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Reference

  1. Chawla G, Gupta P, Koradia V and Bansal AK.  Gastroretension:  A means to address regional variability in intestinal drug absorption. Pharmaceutical Technology.  2003;27:50-68.
  2. Garg Re and Gupta GD.  Progress in controlled gastro retentive delivery systems. Topical Journal of Pharmaceutical Research.  2008;7(3):1055-1066.  
  3. Yadav M, Sharma P, Chaudhary V and Srivastava B. Gastro retentive drug delivery system: a promising approach. Indo   American Journal of Pharmaceutical Research.  2016;6(4):5225-5235.  
  4. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC and Falson Fir. Gastro retentive dosage  forms:  Overview  and  special  case  of Helicobacter pylori. J  Control  Release.  2006;111( 1-2):1 -18.
  5. Patil JM, Hirlekar RS, Gide PS and Kadam VJ.  Trends in floating drug delivery systems.  Journal of Scientific and Industrial Research.  2006;65(1):11-21.
  6. Fujimori J, Machida Y, Tanaka S and Nagai T.  Effect  of  magnetically  controlled  gastric  residence  of  sustained  release  tablets  on  bioavailability  of  acetaminophen. International Journal of Pharmaceutics. 1995;119: 47-55.
  7. Klausner  EA, Lavy  E,  Friedman  M and Hoffmann  A. Expandable gastroretentive dosage forms. Journal of Controlled drug Release.  2003;90:143-162.
  8. Thapa  P and  Jeong  S.  effects of formulation   and  process  variables  on   gastroretentive  floating  tablets  with  a  high- dose  soluble drug  and  experimental  design  approach. Pharmaceutics. 2018;10:1-25.
  9. Gerard J Tortora and Bryan Derrickson. The digestive system: Stomach- Anatomy of the stomach. Anatomy and Physiology. Edited by Wiley. 2015; Indian Edition: 808.
  10. Anne Waugh and Allison Grant. The digestive system: Stomach-Functions of stomach. Ross ans Wilson anatomy and physiology in health and illness. Edited by Elsiver Publications. 2014; 12th Edition: 301.
  11. Pandey   A, Kumar G, Kothiyal P and Barshiliya Y.  Review on current approches in gastroretentive drug delivery system.  Asian Journal of Pharmacy and Medical Science. 2012; 2(4):60-77.
  12. Vyas SP. Controlled drug delivery: Concept and Advances. Vallabh Prakashan. 2006;196-217.
  13. Joseph R.  Controlled drug delivery fundamentals and application. Revised and Expanded Marcell. Dekker Inc. 2nd edition.  New York, 2009.
  14. Khosla R and Davis SS.  The effect of tablet size on the gastric emptying of non-disintegrating tablets.  International Journal of Pharmaceutics. 1990;69:R9- R11.
  15. Deshpandae AA, Rhodes CT, Shah NH and Malick AW. Controlled- release drug delivery systems for prolonged gastric residence. An overview.  Drug delivery Indian Pharmaceutics, 1996;22:531-539.
  16. Abrahamsson  B,  Alpsten  M, Hugosson  M, Jonsson  UE, Sundgren M,  Svenheden  A and Tolli  J.
  17. Absorption,  gastrointestinal  transit, and  tablet  erosin  of felodipine  extended  release  (ER) tablets.  Pharmaceutical Research.1993;10:709.  Oth M, Franz M, Timmermans J and Moes AJ. The bilayer floating capsule:  A Stomach directed drug delivery system         for     misoprostol.  Pharmaceutical research.1992;9:298.
  18. Hermansson   G and Sivertsson R.  Gender- related difference s in gastric emptying rate of solid meals, Digestive Diseases and sciences.  1996;41(10):1994-1998.
  19. Kaus LC, Fell JT, Sharma H and Taylor DC. Gastric emptying and   intestinal transit of non-disintegrating capsules- the influence of metaclopramide.  International Journal of pharmaceutics.1984;22(1):99-103.
  20. Arrora S, Ali J, Khar RK and  Baboota  S.   Floating drug delivery system: A review. AAPSE Pharma Science Technology. 2005;6(3):372-390.
  21. Chawla G, Gupta P and Bansal AK. Gastroretentive drug delivery system. In Jain NK. Editor.  Progress in Controlled and novel drug delivery system CBS Publication and Distributors. New Delhi. 2004;76-97.
  22. Clarke GM, Newton JM and Short MD.Gastrointestinal transit of pellets of differing size and density. International journal pharmaceutics. 1993;100(13):81-92.
  23. Moes AJ. Gastric retention system for oral drug delivery. Business briefing. Pharmatech. 2003;157-159.
  24. Misra SK. Gastrointestinal targetting drug delivery system: A Review. Journal of Pharmacy Research. 2011;4(8):2751- 2754.
  25. Rao  BP, Kottan   NA,  Snehith  VH and  Ramesh  C. Development of  gastroretentive  drug  delivery  system  of  Cephalexin  by  using  factorial  design.  ARE Pharmaceutical. 2009;50: 8.
  26. Sheth PR and Tossounian J. The hydrodyanamically balanced   system. A novel drug   delivery system for oral use.  Drug delivery Indian Pharmaceutics. 2010;3(1):819-833.
  27. Prajapati   VD, Jani GK, Khutliwala TA and Zala BS. Raft forming system - An upcoming approach of gastroretentive drug delivery system. Journal of Control Release. 2013;168: 151-165.
  28. Prinderre P, Sauzet C and Fuxen C.  Advances in Gastro-retentive drug- delivery systems. Expert Opin. Drug delivery. 2011;8:1189-1203.
  29. Chen YC, Ho HO, Lee TY and Sheu MT.  Physical Characterization and sustained release profiling   of gastroretentive drug delivery systems with improved floating and swelling capabilities. International Journal of pharmaceutics. 2013;441:162-169.
  30. Chen J, Blevins WE, Park H and Park K. Gastric retention properties of superporous hydrogel composities. Journal of Control release. 2000;64:39-51.
  31. Kashyap  N, Viswanad  B,  Sharma   G, Bhardwaj  V, Ramarao P and Kumar  MR.  Design and evaluation of biodegradable, biosensitive in situation gelling system for pulsatile delivery of insulin. Biomaterials. 2007;28: 20512060.
  32. Verma S, Nagpal K, Singh S and Mishra D. Unfolding type gastroretentive film of cinnarzine based on ethyl cellulose and hydroxypropyl methylcellulose. Int J Biol Macromol. 2014;64:  347-352.
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                Picture1.jpg
           

       Fig no 1 Anatomy of stomach


            
           
                Picture3.png
           

        
        Fig. 2: Approaches for GRDDS

 



       
            Picture2.jpg
       

    

Fig. 3: Mucoadhesive drug delivery system



       
            Picture4.jpg
       

    

Fig. 4: Effervescent drug delivery system


Table 1:  Drugs used in formulation of GRDDS


       
            Screenshot 2024-05-17 194135.png
       

    


Table 2: Commercially available marketed products


       
            Screenshot 2024-05-17 194225.png
       

    


 

Photo
Pravin Bhimrao Navgire
Corresponding author

Loknete Shri Dadapatil Pharate College Of Pharmacy.

Photo
Nilesh Paraji Musmade
Co-author

Loknete Shri Dadapatil Pharate College Of Pharmacy.

Photo
Amol rajendra Dhayarkar
Co-author

Loknete Shri Dadapatil Pharate College Of Pharmacy.

Photo
V. M satpute
Co-author

Loknete Shri Dadapatil Pharate College Of Pharmacy.

Photo
Ghodake S.R
Co-author

Loknete Shri Dadapatil Pharate College Of Pharmacy.

Pravin Bhimrao Navgire, Nilesh Paraji Musmade, Amol rajendra Dhayarkar, V. M satpute, Ghodake S. R. , Gajanan Sanap Gastro Retentive Drug Delivery Systems: A Review, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 5, 886-896. https://doi.org/10.5281/zenodo.11210033

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