Recent Advance in Gastroretantive Drug Delivery System (GRDDS)

Ashwini A Zanke, Hemant H Gangurde, Ananta B Ghonge, Praful S. Chavan

Institute Name, Shri Sant Gajanan Mharaj College of Pharmacy Buldhana Maharastra 443001, India.

*Corresponding Author E-mail: ashwinizanke98@gmail.com

ABSTRACT:

The drug delivery system is most important and preferable drug delivery system. This route has high patient acceptability, primarily due to easy of administration. Effective oral drug delivery depends upon the factors such as gastric emptying process, the gastrointestinal transit time of the dosage form drug release from the dosage form, and site of absorption of drug. In recent years, scientific and technological advancements have been made in the research and development of gastro retentive drug delivery systems. Hence forth a wide spectrum of dosage forms has been developed for the drugs which have narrow absorption window, unstable at intestinal pH, are soluble in acidic pH, and have a site of action specific to stomach. The purpose of writing this review was to investigate, compile and present the recent as well as past literature in a more concise way with a special focus on approaches that are currently utilized in the prolongation of gastric residence time. These include floating system, swelling and expanding system, bio/mucoadhesive system, high-density system, and other delayed gastric emptying devices. The present review addresses briefly the classification, formulation consideration for Gastroretantive drug delivery system (GRDDS), factors controlling gastric retention, merits, demerits, and applications of gastro retentive drug delivery systems.

KEYWORDS: Gastro retentive drug delivery system, floating system, swelling, expanding system, bio/mucoadhesive system, high-density system, H Pylori infection and its Application.

INTRODUCTION:

Oral delivery of drugs is the most preferred route because of its ease of and low cost of therapy and high level of patient compliance. Oral controlled release drug delivery systems have drawn considerable attention as these systems provide drug release at a predetermined, predictable and controlled rate. However, some drugs show poor bioavailability because of incomplete absorption or degradation in the git^2. Therefore to overcome such problems gastro retentive drug delivery systems are designed to prolong the gastric retention time of the drugs which are:

· locally active in the stomach.

· Unstable the intestinal environment.

· Have a narrow absorption window in the GIT.

· Have low solubility at the high pH regions^.3

Various approaches have been proposed to increase the gastric residence of the drug delivery that includes floating drug delivery system (FDDS), mucoadhesion or bioadhesion system, high-density system, expansion system, magnetic system, super porous hydrogel, raft forming system, and floating ion exchange resins^.4

Potential candidates for gastro retentive drug delivery system:

1. Drugs that are primarily absorbed in the stomach egg Ampicillin.

2. Drugs those are poorly soluble in alkaline pH egg Furosemide, Diazepam.

3. Drugs that have narrow absorption window egg Levodopa, Methotrexate.

4. Drugs that degrade in the colon egg. Ranitidine, Metformin HCL.

5. Drugs that disturb normal colonic microbes egg Antibiotics against Helicobacter pylori.

6. Drugs rapidly absorbed from the GI tract egg Tetracycline.

7. Drugs acting locally in the stomach ⁵

Limitations of gastro retentive drug delivery system:

1. Aspirin and NSAID’S can cause gastric lesions and slow release of such drug in the stomach is unwanted.

2. Drugs such as isosorbide denigrate which are equally absorbed throughout the GIT will not be benefit from incorporation into a gastric retention system.

3. Bioadhesion in the acidic environment and high turnover of mucus may raise questions about the effectiveness of the technique

4. Physical integrity of the system is very important and primary requirement for the success of the system.

5. High variability in gastric emptying time due to variations in emptying process, unpredictable bioavailbility^.6,7

Anatomy of the stomach:

The gastro intestinal tract can be divided into three main regions

• Stomach

• Small intestine- duodenum, jejunum, and ileum

• Large intestine

The GIT is a muscular tube of about 9 m which extends from mouth to anus. Its function is to take nutrients and eliminate out waste product by physiological processes such as digestion, absorption, secretion, motility and excretion. The stomach has three muscle layer called oblique muscle and it is situated in the proximal part of the stomach, branching over the fundus and higher regions of the gastric body. The stomach is divided into fundus, body and pylorus^8. The stomach is a J shaped organ located in the upper left hand portion of the abdomen. The main function of the stomach is to store the food temporarily, grind it and releases slowly in to the duodenum. Physiology of the stomach The stomach is an expanded section of the digestive tube between the oesophagus and small intestine. In the empty state the stomach is contracted and its mucosa and sub mucosa are thrown up into folds called reggae.

There are 4 major types of secretory epithelial cells that cover the stomach and extends into gastric pits and glands.

1. Mucous cells- secrete alkaline mucus

2. Parietal cells – secrete HCL

3. Chief cells- secrete pepsin

4. G cells- secrete hormone gastrin^9.

Factors affecting gastric retention Density:

Density:

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

Size:

Dosage form having diameter of more than 7.5mm have more gastric residence time than that of 9.9 mm diameter dosage form. Shape of the dosage form. The tetra hadron resided in the stomach for a longer period than other devices of similar size. Single or multiple unit formulation- multiple unit formulation shows a more predictable release profile and insignificant impairing of the performance due to failure of the units. allow co-administration of units with different release profiles or containing incompatible substances and permit a larger margin of safety against dosage form failure compared with single unit dosage form ^12.

Fed or unfed state:

Under fasting conditions, the gig motility is characterized by periods of strong motor activity that occur every 1.5-2 hrs. the MMC sweeps undigested material from 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 a fast state MMC is delayed and GRT is longer.

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^.13

Caloric Content:

GRT can be increased by 4-10 with a meal that is high in protein and fat^14. Frequency of feed: The GRT can be increased over 400 min when successive meals are given are compared with the single meal due to the low frequency of MMC. Gender: Mean ambulatory GRT in males (3.4hrs) is less compared with the age and race-matched female counterparts (4.6hrs) regardless of height, weight, and body surface. Age: People with age more than 70 have a significantly longer GRT^15. Concomitant drug administration- anticholinergics like atropine and propantheline, opiates like codeine can prolong GRT^2,15 Gastroretentive dosage form Gastroretentive dosage forms are the systems that can stay in the gastric region for several hours and thus, prolong the gastric residence time of the drugs. After oral administration, such a dosage form is retained in the stomach and releases the drug in a controlled and sustained manner so that the drug can be supplied continuously in the upper GIT. This prolonged gastric retention improves bioavailability, decreases drug wastage, and improves the solubility of drugs that are less soluble in a high pH environment.¹⁶

Classification of GRDF:

a) High-density system

b) Floating system

c) Expandable system

d) Super porous hydrogels

e) Mucoadhesive bioadhesive system

F) Magnetic system

High density system:

This approach involves formulation of dosage forms with density that must exceed density of normal stomach content 1.004g/ml. these formulations are prepared by coating drug on a heavy core or mixed with heavy inert material such as iron powder, zinc oxide, titanium dioxide, barium sulphate. The resultant pellets can be coated with diffusion controlled membrane¹⁷

Floating or low-density system

by their low densities, FDDS remain afloat above the gastric contents for prolonged periods and provide continuous release of the drug. These systems in particular have been extensively studied because they do not adversely affect the motility of the GIT. Their dominance over the other types of GRRDS is also evident from the large number of floating dosage forms being commercialized and marketed worldwide.¹⁸

Volatile liquid containing system The GRT of a drug delivery system can be sustained by incorporating an inflatable chamber, which contains a liquid e.g. ether, cyclopentane, that basifies at body temperature to cause the inflation of the chamber in the stomach. The device may also consist of a bio erodible plug made up of Polyvinyl alcohol, Polyethylene, etc. that gradually dissolves causing the inflatable chamber to release gas and collapse after a predetermined time to permit the spontaneous ejection of the inflatable systems from the stomach²⁰

Gas-generating Systems:

These buoyant delivery systems utilize effervescent reactions between carbonate/bicarbonate salts and citric/tartaric acid to liberate CO2, which gets entrapped in the jellified hydrocolloid layer of the system thus decreasing its specific gravity and making it float over gastric content.

Non-Effervescent FDDS:

The Non-effervescent FDDS is based on the mechanism of swelling of polymer or bioadhesion to mucosal layer in GI tract. The most commonly used excipients in non-effervescent FDDS are gel-forming or highly swell able cellulose-type hydrocolloids, hydrophilic gums, polysaccharides, and matrix-forming materials such as polycarbonate, polyacrylate, polymethacrylate, polystyrene as well as bioadhesive polymers such as Chitosan^.21

Mucoadhesive systems:

Mucoadhesive drug delivery systems contain a mucoadhesive polymer that adheres to the gastric mucosal surface and prolongs its gastric retention in the git. The capability to adhere to the mucus gel layer makes mucoadhesive polymers very useful excipients in the GRRDS. These polymers can be natural such as sodium alginate, gelatine, guar gum, etc. semisynthetic polymers such as HPMC, carpool, sodium carboxymethyl cellulose^22. The adhesion of polymers with mucous membrane may be mediated by hydration, bonding, or receptor-mediated. In hydration-mediated adhesion, the hydrophilic polymer becomes sticky and mucoadhesive upon hydration. Bonding mediated involves mechanical or chemical bonding. Chemical bonds may involve ionic or covalent bonds or van der Waal forces between the polymer molecule and the mucous membrane. Receptor-mediated adhesion takes place between certain polymers and specific receptors expressed on gastric cells. The polymers can be cationic or anionic or neutral^23.

Swelling system:

These are the dosage forms, which after swallowing swells to such an extent that their exit from the pylorus is prevented as a result; the dosage form is retained in the stomach for a prolonged period. These systems are called as plug type systems as they tend to remain lodged at the pyloric sphincter. The formulations are designed for gastric retention and controlled delivery of drugs in the gastric cavity, such formulations remain in the gastric cavities for several hours even in the fed state. Controlled and sustained release may be achieved by selection of proper molecular weight polymer, and swelling of the polymers retard the release ^24. On coming in contact with gastric fluid the polymer imbibes water and swells. The extensive swelling of these polymers is due to the presence of physical-chemical cross-links in the hydrophilic polymer network. These cross-links prevent the dissolution of the polymer and hence maintain the physical integrity of the dosage form. An optimum cross-linking, which maintains a balance between the swelling and the dissolution, should be maintained. Aguilera developed a polymeric coating system that formed an outer membrane on the conventional tablets. In the dissolution media, the membrane detached from the core and swelled to form a balloon that kept the unit floating. The size of the units increased by three to six-folds, thus the floating ability as well as the increased dimension offered the system gastro retentive property ²⁵

Magnetic system:

This system is based on the simple idea that the dosage form contains a small internal magnet and a magnet placed on the abdomen over the position of the stomach. Using an extracorporeal magnet, the gastric residence time of the dosage form can be enhanced for a prolonged period ²⁸ Invitro method of evaluation

In vitro method of evaluation:

Fourier transform infrared analysis Fourier transform infrared spectroscopy is mostly used to identify the organic, polymeric, functional groups, and some inorganic materials as well. FT-IR measurements of pure drug, polymer, and drug-loaded formulations are obtained by using this technique ^29. The pellets are prepared on kb press under hydraulic pressure of 150kg/cm2 and the spectra are scanned over the wavenumber range of 3600-400cm-1 at ambient temperature ^30.

Differential scanning calorimetric DSC:

Are performed to characterize water of hydration of pharmaceuticals. Thermo grams of formulated preparations are obtained using a DSC instrument equipped with intercooler zinc standards are used to calibrate the DSC temperature and enthalpy scale^31. The sample preparations are sealed in an aluminium pan and heated at a constant rate of 10 ºC/min over a temp range of 25ºC-65ºC^32. Particle size analysis and surface characterization (for floating microspheres and beads) The particle size and size distribution of beads or microspheres are determined in the dry state using the optical microscopy method. The external and cross-sectional morphology is done by scanning electron microscope^33-34. Floatation studies The in-vitro buoyancy is characterized by floating lag time and total floating time^35. The FLT and TFT are measured by placing the tablets in a 250 ml beaker Particle size analysis and surface characterization (for floating microspheres and beads) The particle size and size distribution of beads or microspheres are determined in the dry state using the optical microscopy method. The external and cross-sectional morphology is done by scanning electron microscope^33-34

Drug Dosage form Approaches for gastro retention:

To improve the retention of an oral dosage form in the stomach various approaches have been developed, it includes floating systems and non-floating systems. Floating systems include effervescent systems and non-effervescent systems, these systems have the bulk density lower than the gastric fluid and remain floating and release the drug slowly at the desired rate. Non floating systems include bioadhesive systems, swelling systems, high-density systems expandable systems, raft forming systems, magnetic systems which utilize different mechanisms to prevent the exit of drugs through pyloric sphincters^{. 28}Suitable drug candidates for gastro retention delivery system It is evident from the recent scientific and patient literature that an increased interest in novel dosage forms that are retained in the stomach for a prolonged and predictable period exists today in academic and industrial research groups. One of the most feasible approaches for achieving a prolonged and predictable drug delivery in the GI tract is to control the gastric residence time, i.e. gastro retentive delivery system. Gastric retention is enhanced the therapeutic effect of the drugs due to improving the oral drug absorption in the stomach. Drugs are released from the formulations in a controlled manner so that reduce dosing frequency and improve patient compliance. Suitable drug candidates for gastric retention delivery systems are shown

Table 1: List of Drugs Formulated in Multiple Unit Forms of Floating Drug Delivery Systems

Drug Dosage form	Drug Dosage form
Verapamil Hydrochloride	Floating Micro particles
Ketoprofen Floating	Micro particles
Ranitidine Hydrochloride Floating Granules	Ranitidine Hydrochloride Floating Granules
Metronidazole Floating Beads	Metronidazole Floating Beads
Lansoprazole Floating Micro pellets	Lansoprazole Floating Micro pellets
Meloxicam	Low density multi particulate system
Diltiazem Hydrochloride, Theophylline & Verapamil Hydrochloride	Theophylline and Micro particles
Nifedipine Hollow Microsphere	Acetohydroxamic Acid Floating Microsphere
Piroxicam Floating Microsphere Residronate Sodium Granules	Diltiazem Hydrochloride Granules
Piroxicam Floating Microsphere	Residronate Sodium Granules

Approaches for gastro retention:

Suitable drug candidates for gastro retention delivery system It is evident from the recent scientific and patient literature that an increased interest in novel dosage forms that are retained in stomach for a prolonged and predictable period of time exists today in academic and industrial research groups. One of the most feasible approaches for achieving a prolonged

Table:2: Poorly soluble at an alkaline pH

Ranitidine	Anti-Histamine
Good absorption at stomach
chlordiazepoxide	Antipsychotic
Cinnarizine	Anti-allergy
Narrow absorption window
Levodopa	Anti epilepsy
Riboflavin	Vitamin
Drug degradation at colon
Ranitidine HCl	Antiulcer
Metronidazole	Antimicrobial
Amoxicillin	Antibiotic
Poor solubility in water
Acyclovir	Antiviral
Silymarin
Norfloxacin	Antibiotic
Ciprofloxacin	Antibiotic
Ofloxacin	Antibiotic
High solubility in acidic pH
Dipyridamole	Antiplatelet
Locally acting at stomach
Misoprostol	Anti-Ulcer

Application of gastric retention delivery systems on the treatment of H. pylori infection:

Helicobacter pylori (H. pylori) is one of the most common pathogenic bacterial infections, colonizing an estimated half the world’s population. It is associated with the development of the serious gastroduodenal disease—including peptic ulcers, gastric lymphoma, and acute chronic gastritis. is shown as a clear representation of the mechanism of H. pylori-induced gastric ulcer. H. pylori reside mainly in the gastric mucosa or at the interface between the mucous layer and the epithelial cells of the antral region of the stomach. H. pylori Genomes have been linked to altered gastric acid secretion and premalignant histological features. The discovery of this microorganism has revolutionized the diagnosis and treatment of peptic ulcer disease. Most antibacterial agents have low minimum inhibitory concentrations (MIC) against H. pylori in culture. And, single antibiotic therapy is not effective for the eradication of H. pylori infection in vivo. This is because of the low concentration of the antibiotic reaching the bacteria under the mucosa, instability of the drug in the low pH of gastric fluid, and short residence time of the antibiotic in the stomach. A combination of more than one antibiotic and an anti-secretory agent is required for the complete eradication of H. pylori, but these regimens are not fully effective. Patient compliance, side effects, and bacterial resistance are the other problems. Other than the multi-antibiotic therapy, different therapeutic strategies have been examined to completely eradicate H. pylori from the stomach²⁴

Table:3: used drug in formulation of gastro retentive dosages forms ^37,38

Dosage forms	Drugs
Floating Tablets	Diltiazem, Fluorouracil, Isosorbide dinitrate, Isosorbid mononitrate, Aminobenzoic acid(PABA), Prednisolone, Nimodipine, Sotalol, Theophylline, Verapamil
Floating Capsules	Chlordiazepoxide HCl, Diazepam, Furosemide, L-DOPA and Benserazide, Nicardipine, Misoprostol, Propranolol, Pepstatin
Floating Microspheres	Aspirin, Griseofulvin, p-nitro aniline, Ibuprofen, Terfenadine, Tranilast
Floating Granules	Diclofenac sodium, Indomethacin, Prednisolone
Powders Several	basic drugs Films Cinnerzine

Table 4: Gastroretentive products available in the market ³⁹

Brand Name	Active Ingredient(s)
Cifran OD X	Ciprofloxacin
Madopar	L-DOPA and
Valrelease	Benserazide
Topalkan	Diazepam
Almagate FlatCoat	Aluminum -magnesium antacid
Liquid Gavison	Aluminium hydroxide,
Conviron Cytotec	Ferrous sulfate Misoprostal

Nanoparticles:

The concept of nano particulate much-penetrating drug delivery system was developed complete eradication of Helicobacter pylori (H. pylori), colonized deep into the gastric mucosal lining. Due to nanoparticles having dual activity of adhesion and penetration of drugs into the mucous layer 40 was developed pH-responsive chitosan/heparin nanoparticles were by the addition of heparin solution to a chitosan solution with magnetic stirring at room temperature. The nanoparticles appeared to have a particle size of 130–300nm, with a positive surface charge, and were stable at pH 1.2–2.5, allowing them to protect an incorporated drug from destructive gastric acids. Nanoparticles adhered to and infiltrate cell-cell junctions and interact locally resulting that significantly controlling H. pylori infections.40,41 Existing patented gastric retention drug delivery system suitable for the treatment of H. pylori infection has outlined in the.

Table 3: List of various Patents

Sr No	Patent No	Type Of Formulation	Year
1	US 5769638	Buoyant controlled release powder formulation	1992
2	US 5198229	Self-retaining GIT delivery device	1993
3	US 5232704	Sustained-release bilayer buoyant dosage form	1993
4	US 5626876	Floating system for oral therapy	1997
5	US 6207197	Gastro-retentive controlled-release microspheres	2001
6	US 8277843	Programmatic buoyant delivery technology 2012	2012
8	US 8808669	GR extended release composition of the therapeutic agent	2014
9	US 9314430	Floating GR dosage form	2016
10	US 9561179	Controlled release floating pharmaceutical compositions	2017
		Patents on mucoadhesive or bio adhesive systems
11	US 5472704	Pharmaceutical CR composition with bioadhesive properties	1995
12	US 5900247	Mucoadhesive for CR of the active principle	1999
13	US 6303147	Bioadhesive solid dosage form	2001
14	US 6306789	Mucoadhesive granules of carbomer suitable for oral administration of drugs	2001
15	US 8974825	A pharmaceutical composition for the GI drug delivery	2015
		Patents on swelling and expandable systems
16	US 4767627	Gastric retaining drug delivery device for controlled delivery of drugs	1988
17	US 5443843	GRDDS for controlled release of drug	1995
18	US 5443843	GRDDS for controlled release of drug	1995
19	US 5780057	Pharmaceutical tablet exhibiting high volume increase when gets in contact with gastric fluids	1998
20	US 5972389	Gastro-retentive, an oral dosage form for CR of sparingly soluble drugs	1999
21	US 6488962	Tablets shape to enhance gastric retention	2002
22	US 6548083	Prolonged-release drug delivery device adapted for gastric retention 2003	2003
23	US 6635280	Dosage form extending the duration of drug release in the gastric region during fed mode	2003
24	US 6723340	Optimal polymer retentive tablets release of acamprostate	2004
25	US 6776999	Expandable GR therapeutically system for prolonged gastric retention time	2004
26	US 7976870	Gastro-retentive oral dosage form with restricted drug release in lower GIT	2011
27	US9393205	GR tablets	2016
28	US9801816	GR dosage form extended-release of acamprostate	2017
		Patents on raft forming systems
29	US 0119994	Gastric raft composition	2001
30	2. US 0063980	In situ gel formation of pectin	2002
		Other patents related to GRDDS
31	US 6635281	The gastric retaining liquid dosage form	2003
32	US 6797283	Gastric retaining dosage form having multiple layers	2004
33	US 8586083	GRDDS comprising an extruding hydratable polymer	2013
34	US 9119793	GR dosage form of doxycycline	2015
35	US201503668	GR tablets of pregabalin	2015
35	US201502310	Osmotic floating tablets	2015
36	US201603389	Stabilized GR tablets of pregabalin	2016

CONCLUSION:

Gastro retentive drug delivery systems offer various potential advantages for a drug with poor bioavailability due to their absorption being restricted to the upper gastrointestinal tract (GIT) and they can be delivered efficiently thereby maximizing their absorption and enhancing absolute bioavailability. One of the main applications of gastric retention drug delivery system on treatment of H. pylori infection is a promising area of research in the pharmaceutical industry and academia. Based on the literature, we concluded that the gastric retention drug delivery system has more scope to file patents and a lot of opportunities available to market the product which has more patient compliance.

REFERENCE:

1. Basak SC, Rao NK, Manavalan R, Rao RP. Development and invitro evaluation of an oral floating matrix tablet formulation of ciprofloxacin. IJPS, 2004;66(3):313-316.

2. Streubel A, Siepmann, Bodmeir J. Drug delivery to the upper intestine window using gastroretentive technologies. Curr Opin Pharmacol, 2006:6:501-508.

3. Chen YC, Ho H, Lee TY, Sheu MT. Physical characterizations and sustained release profiling of gastroretentive drug delivery system with improved floating and swelling capabilities. International Journal Of Pharmaceutics, 2013;44: 162-169.

4. Prajapati DV, Jani GK, Khutliwala TA, Zala BS. Raft forming system- An upcoming approach of gastroretentive drug delivery system. Journal of Controlled Release, 2013; 168:151-165.

5. Subhramananyam CVS, Setty JT. Laboratory manual of physical Pharmaceutics. Vallabh Prakashan 2002; pg no 212.

6. Vinod KR, Vasa S, Anbuazagahan S. Approaches for gastroretentive drug delivery, IJABPT, 2008;589-601.

7. Pawar V.K, Shaswat K, Garg G, Awasthi R. Gastroretentive dosage form: A review with special emphasis on floating drug delivery systems, Informa Healthcare 2011;18(2):97-110

8. Dixit N. Floating drug delivery system. Journal of Current Pharmaceutical Research, 2011;7(1):6-20.

9. Robinson J, Lee R. Controlled Drug Delivery, 2 nd edition, 1987: pg 418.

10. Bardonnet PL, Faivre V, Pugh WJ, Piffaretti JC, Falson F. Gastroretentive dosage forms. Journal of Controlled Release, 2006; 111:1-18.

11. Arora S, Javed A, Ahuja A, Khar RK, Baboota S. Floating drug delivery system: a review. AAPS Pharm Sci Tech, 2000;6(3):372-390.

12. Patel GM, Patel HR, and Patel M. Floating drug delivery system an innovative approach to prolong gastric retention. Pharmainfo.net 2007

13. Arora S, Javed A, Ahuja A, Khar RK, Baboota S. Floating drug delivery system: a review. AAPS Pharm Sci Tech, 2000;6(3):372-390.

14. Patel GM, Patel HR, and Patel M. Floating drug delivery system an innovative approach to prolong gastric retention. Pharmainfo.net 2007.

15. Garg AK, Kapoor G, Sachdeva RK. Formulation and evaluation of nizatidine floating tablets. American Journal of pharmatech Research, 2012;2(5):504-515.

16. Singh B and Kim KH. Floating drug delivery system: an approach to oral controlled drug delivery system via gastric retention. Journal of Controlled Release, 2000;63:235-259.

17. Waterman KC. A critical review of gastric retentive controlled drug delivery. Pharmaceutical Development and Technology, 2007;12: 1-10.

18. Kotreka U and Adeyeye MC. Gastroretentive floating drug delivery system a review. Therapeutic Drug Carrier System, 2011; 28(1):47-99.

19. Mayavanshi AV and Gajjar SS. Floating drug delivery system to increase gastric retention of drugs. RJPT, 2008;1(4):345-348.

20. Jamil F, Sunil K, Sharma S, Vishvakarma P, Singh L. Review on stomach specific drug delivery: development and evaluation. IJRPBS, 2011;2(4):1427-1433.

21. Talukder R, Fassihi R. Gastroretentive delivery systems. Drug development and industrial pharmacy,2004;30(10):1019-1028.

22. Krogel I and Bodmeier R. floating or pulsatile drug delivery system based on coated effervescent cores. International Journal of Pharmaceutics, 1999;187:175-184.

23. Groning R, Heun C. Oral dosage forms with controlled gastrointestinal transit drug delivery, 1984;10(4):527-539.

24. 25. Agyilirah GA, Green M, Ducret R. Evaluation of gastric retention properties of cross linked polymer- coated tablet versus those of non disintegrating tablets. Int J Pharma. 1991; 75:241-247

25. Despande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled release system for gastric retention. Pharmaceutical Research,1997;14(6):815-819

26. Nayak AK, Magi R, Das B. Gastroretentive drug delivery system a review. Asian Journal of Pharm Clan Res.2010;3(1):2-10.

27. Santander Kaka, Deepak Bart, Raman deep Singh, Ujjwal Nautiyal. Magnetic microspheres as magical novel drug delivery system: A review. Journal of Acute Disease 2013:1-12

28. Girish S, Sonar, Devendra K, Jain, Dhananjay M. Preparation and invitro evaluation of bilayer floating bioadhesive tablets of Rosiglitazone Maleate. Asian Journal of Pharmaceutical Sciences.2007;2(4):161-169.

29. Sruthy PN and Anoop KR. Formulation and evaluation of olmesartan medoxomil floating tablets. International Journal of Pharmacy and Pharmaceutical Sciences, 2013;5(3):691-696.

30. Pawar HA, Gharat PR, Dhavale RV, Joshi PR, Rakshit PP, Development and evaluation of gastroretentive floating tablets of an antihypertensive drug using hydrogenated cottonseed oil. ISRN, 2013;10(11):1-9.

31. Khan AZ, Tripathi R, Mishra B. Floating elementary osmotic pump tablet for controlled d delivery of diethylcarbamazine citrate: a watersoluble drug. AAPS Pharm Sci Tech, 2011;12(4):1312-1323.

32. Subhramananyam CVS, Setty JT. Laboratory manual of physical pharmaceutics. Vallabh prakashan 2002;pg no 212.

33. Tanwar YS, Naruka PS, Ojha GR. Development and evaluation of floating microspheresof verapamil HCL. BJPS,2007;43(4):529-534.

34. Kharkhile VG, Karmarkar RR, Sontakke MA, Badgujar SD, Nemade LS. Formulation and evaluation of floating tablets of furosemide. International Journal of Pharma. Research and Development, 2012;(12):1-9.

35. Chinthala SK, Kota SR, Hadassah M, Metilda, Sridevi S. Formulation and evaluation of gastroretentive floating tablets of gabapentin using effervescent technology. Int J Pharm Biomed Res, 2012;3(4):202-208.

36. Arrora S, Ali J, Khar RK, Baboota S. Floatng drug delivery systems: A review. AAPS Pharm Sci Tech 2005; 6(3): 372-90.

37. Vyas SP, Khar RK. Gastroretentive systems. In: Controlled drug Delivery. Vallabh Prakashan, Delhi, India. 2006. p. 197-217

38. Chawla G, Gupta P, Bansal AK. Gastroretentive drug delivery systems. In: Jain NK. editor. Progress in controlled and novel drug delivery systems. CBS Publishers and Distributors. New Delhi. 2004. p. 76-97.

39. Lin YH, Chang CH, Wu YS, et al. Development of pH–responsive chitosan/heparin nanoparticles for stomach–specific anti–Helicobacter pylori therapy. Biomaterials. 2009;30 (19):3332–3342.

40. GO MF. Review article: natural history and epidemiology of Helicobacter pylori infection. Aliment Pharmacol Ther. 2002; 16:3–15.

41. Jain P, Jain S, Prasad KN, et al. Polyelectrolyte coated multilayered liposomes (nanocapsules) for the treatment of Helicobacter pylori infection. Mol Pharm. 2009;6(2):593–603.

Received on 05.12.2021 Modified on 10.02.2022

Asian J. Pharm. Res. 2022; 12(2):143-149.

DOI: 10.52711/2231-5691.2022.00022