INTRODUCTION:

Oral delivery of drugs is the most preferred administration route due to ease of administration. Drug bioavailability of pharmaceutical oral dosage forms is influenced by various factors. One important factor is the gastric residence time (GRT) of these dosage forms. [1, 2] It has been estimated that about 40–70% of all new drug candidates merging from drug discovery programs exhibit low solubility in water, resulting in poor oral bioavailability due to insufficient dissolution along the gastrointestinal (GI) tract [3]. Absorption of drug from gastrointestinal tract (GI) is a complex procedure and is subjected to many variables. [4] These variables make the in-vitro performance of the drug delivery systems uncertain. [5]

The need for gastro retentive dosage forms (GRDFs) has led to extensive efforts in both academia and industry towards the development of such effective drug delivery systems. [6] Prolonging the gastric residence of a dosage form may be of therapeutic value. The process and ability to prolong and control the emptying time is a valuable asset for dosage forms, which reside in the stomach for a longer period of time than the available conventional dosage forms [7] these physiological problems have been overcome by several drug delivery systems, by investigating the prolonged gastric retention time. [8, 9] The basic idea behind the development of such a system is to maintain a constant level of drug in the blood plasma in spite of the fact that the drug does not undergo disintegration.

Several approaches have been proposed to retain the dosage forms in the stomach. These approaches used for the formulation of gastro retentive systems are mucoadhesion (bioadhesive system) [10, 11] flotation, sedimentation, [12, 13] expansion, [14, 15] and modified shape systems [16, 17] or by the simultaneous administration of pharmacological agents. [18, 19] The controlled gastric retention of solid dosage forms may be achieved, which delay gastric emptying. In fact the buoyant dosage unit enhances gastric residence time (GRT) without affecting the intrinsic rate of emptying.

The classification of different modes of gastric retention is listed below: [20, 21]

· high-density (sinking) systems,

· low-density (floating) systems,

· expandable systems,

· super porous hydro gel systems,

· mucoadhesive systems

· Magnetic systems.

Both single-unit systems (tablets or capsules) and multiple-unit systems (multi particulate systems) have been reported in the literature. [22] HBS (Hydro dynamically balanced system), single unit form are unreliable in prolonging the GRT owing to their ‘all- or- nothing’ emptying process and, thus they may causes high variability in bioavailabity and local irritation due to large amount of drug delivered at a particular site of the gastrointestinal tract. [23] Amongst the methods available to achieve this, floating dosage forms show considerable promise. [24] FDDS offer the most effective and rational protection against early and random gastric emptying compared to the other methods proposed for prolonging the gastric residence time (GRT) of solid dosage forms. [25]

Extended-release dosage forms with prolonged residence time in the stomach are also highly desirable for drugs that are locally active in the stomach and those are unstable in the intestinal or colonic environment or which have low solubility at higher pH values. [26] FDDS has a lower density than gastric fluid and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. Effervescent floating dosage forms prepared with the help of swellable polymers such as methylcellulose and various effervescent compounds such as sodium bicarbonate, tartaric acid, and citric acid. They are formulated in such a way that when in contact with the acidic gastric contents, CO₂ is liberated and gets entrapped in swollen hydrocolloids, which provides buoyancy to the dosage forms. [27]

Composition and Physiology of Stomach and GIT:

The gastrointestinal tract is essentially a tube about nine metres long that runs through the middle of the body from the mouth to the anus and includes the throat (pharynx), oesophagus, stomach, small intestine (consisting of the duodenum, jejunum and ileum) and large intestine (consisting of the cecum, appendix, colon and rectum).

The stomach is divided into 3 anatomic regions: fundus, body, and antrum (pylorus). The separation between stomach and duodenum is the pylorus. The part made of fundus and body acts as a reservoir for undigested material, whereas the antrum is the main site for mixing motions and act as a pump for gastric emptying by propelling actions. Gastric emptying occurs during fasting as well as fed states. The pattern of motility is however distinct for the two states. During the fasting state an inter digestive series of electrical events take place, which cycle both through stomach and intestine every 2–3 hrs. This is called the interdigestive myloelectric cycle or migrating myloelectric cycle (MMC), which is further divided into following 4 phases. [28]

· Phase I (basal phase) lasts from 40 to 60 minutes with rare contractions.

· Phase II (preburst phase) lasts from40 to 60 minutes with intermittent action potential and contractions. As the phase progresses the intensity and frequency also increases gradually.

· Phase III (burst phase) lasts for 4–6 minutes. It includes intense and regular contractions for short period. It is due to this wave that all the undigested material is swept out of the stomach down to the small intestine. It is also known as the housekeeper wave.

· Phase IV lasts for 0–5 minutes is a transition period of decreasing activity until the next cycle begins.

Different Features of Stomach:

Gastric pH: Fasted healthy subject 1.1 ± 0.15, Fed healthy subject 3.6 ± 0.4

Volume : Resting volume is about 25-50 ml

Gastric secretion: Acid, pepsin, gastrin, mucus and some enzymes about 60 ml with approximately 4 mmol of hydrogen ions per hour.

Gastrointestinal Transit Time:

The residence time of liquid and solid foods in each segment of the GI tract is different. Since most drugs are absorbed from the upper intestine (duodenum, jejunum, and ileum), the total effective time for drug absorption is 3-8 hrs. This is why one has to take most drugs 3-6 times a day.

Table 1: Residence time of different type of food in GIT

Segment	Type of food
Segment	Solid	Liquid
Stomach	10-30 minutes	1-3hrs
Duodenum	60 secs	60 secs
Jejunum and ileum	3hrs ±15hrs	4hrs ±105hrs
Colon	-	20-50 hrs

Need of GRDDS:

Gastro-retentive dosage forms have been the topic of interest in recent years as a practical approach in drug deliveries to the upper GI tract or for release prolongation and absorption. [29, 30, 31] Food effects and the complex motility of the stomach play a major role in gastric retention behavior. [32] Most of the drugs have their greatest therapeutic effect when released in the stomach, particularly when the release is prolonged in a continuous, controlled manner. Drugs delivered in this manner have a lower level of side effects and provide their therapeutic effects without the need for repeated dosages or with a low dosage frequency. Sustained release in the stomach is also useful for therapeutic agents that the stomach does not readily absorb, since sustained release prolongs the contact time of the agent in the stomach or in the upper part of the small intestine, which is where absorption occurs and contact time is limited. Furthermore, improved bioavailability is expected for drugs that are absorbed readily upon release in the GI tract. These drugs can be delivered ideally by slow release from the stomach. Many drugs categorized as once-a-day delivery have been demonstrated to have suboptimal absorption due to dependence on the transit time of the dosage form, making traditional extended release development challenging. Therefore, a system designed for longer gastric retention will extend the time within which drug absorption can occur in the small intestine. [33]

Suitable drug candidate for gastro retentive delivery system:

1. Drugs acting locally in the stomach, E.g. Antacids and drugs for H. Pylori viz., Misoprostol

2. Drugs that are primarily absorbed in the stomach, E.g. Amoxicillin

3. Drugs that is poorly soluble at alkaline pH, E.g. Furosemide, Diazepam, Verapamil, etc.

4. Drugs with a narrow window of absorption, E.g. Cyclosporine, Methotrexate, Levodopa, etc.

5. Drugs which are absorbed rapidly from the GI tract, E.g. Metonidazole, tetracycline.

6. Drugs that degrade in the colon, E.g. Ranitidine, Metformin HCl.

7. Drugs that disturb normal colonic microbes, E.g. antibiotics against Helicobacter pylori.

Drugs unsuitable for gastroretentive drug delivery system:

1. Drugs that have very limited acid solubility, E.g. phenytoin etc.

2. Drugs that suffer instability in the gastric environment, E.g. erythromycin etc.

3. Drugs intended for selective release in the colon, E.g. 5- amino salicylic acid and corticosteroids etc.

Figure 2: comparison of drug absorption between conventional dosage form and gastro retentive drug delivery system.

Advantages of Gastro retentive Delivery Systems:

· Improvement of bioavailability and therapeutic efficacy of the drugs and possible reduction of dose e.g. Furosemide

· Maintenance of constant therapeutic levels over a prolonged period and thus reduction in fluctuation in therapeutic levels minimizing the risk of resistance especially in case of antibiotics. e.g. b-lactam antibiotics (penicillins and cephalosporins)

· Retention of drug delivery systems in the stomach prolongs overall.

· Gastrointestinal transit time thereby increasing bioavailability of sustained release delivery systems intended for once-a-day administration. e.g. Ofloxacin. [34]

Limitations of Gastro retention:

More predictable and reproducible floating properties should be achieved in all the extreme gastric conditions. [35]

1. The floating systems in patients with achlorhydria can be questionable in case of swellable systems, faster swelling properties are required and complete swelling of the system should be achieved well before the gastric emptying time.

2. Bioadhesion in the acidic environment and high turnover of mucus may raise questions about the effectiveness of this technique. Similarly retention of high density systems in the antrum part under the migrating waves of the stomach is questionable.

3. Not suitable for drugs that may cause gastric lesions e.g. Non- steroidal anti inflammatory drugs. Drugs that are unstable in the strong acidic environment, these systems do not offer significant advantages over the conventional dosage forms for drugs that are absorbed throughout the gastrointestinal tract.

4. The mucus on the walls of the stomach is in a state of constant renewal, resulting in unpredictable adherence.

5. Require a higher level of fluids in the stomach.

In all the above systems the physical integrity of the system is very important and primary requirement for the success of these systems.

Factors affecting gastric retention time of the dosage form:

1. Size and Shape of dosage form:

In designing an indigestible single unit solid dosage form, shape and size of the dosage forms plays a vital role. The mean gastric residence times of non floating dosage forms are highly variable and greatly dependent on their size, which may be large, medium and small units. In most of the cases, the larger the dosage form the greater will be the gastric. Tetrahedron and ring shaped devices with a flexural modulus of 48 and 22.5 kilo pounds per square inch (KSI) are reported to have better GRT ≈90% to 100% retention at 24 hours compared with other shapes. Dosage form units with a diameter of more than 7.5mm are reported to have an increased GRT compared with those with a diameter of 9.9mm. [36]

2. Single or multiple unit formulation:

Multiple unit formulations possess a more Predictable release profile and insignificant impairing of performance due to failure of units allow co- administration of units with different release profiles or containing incompatible substances and also permit a larger margin of safety against dosage form failure compared with single unit dosage forms.

3. Density:

GRT (Gastric retention time) is a function of dosage form buoyancy that is dependent on the density. The density of a dosage form also affects the gastric emptying rate and determines the location of the system in the stomach. Dosage forms having a density lower than the gastric contents can float to the surface, while high density systems sink to bottom of the stomach. Both positions may isolate the dosage system from the pylorus. A density of < 1.0 gm/ cm³ is required to exhibit floating property.

4. Fed or unfed state:

Under fasting conditions: GI motility is characterized by periods of strong motor activity or the migrating myoelectric complex (MMC) that occurs every 1.5 to 2 hours. The MMC sweeps undigested material from the stomach and, if the timing of administration of the formulation coincides with that of the MMC, the GRT of the unit can be expected to be very short. However, in the fed state, MMC is delayed and GRT is considerably longer. [37]

5. Frequency of feed:

The GRT can increase by over 400 minutes, when successive meals are given compared with a single meal due to the low frequency of MMC.

6. Nature of meal:

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

7. Other factors

a. Caloric content: GRT can be increased by 4 to 10 hours with a meal that is high in proteins and fats.

b. Age: Elderly people, especially those over 70, have a significantly longer GRT.

c. Posture: GRT can vary between supine and upright ambulatory states of the patient.

d. Gender: Mean ambulatory GRT in males (3.4±0.6 hours) is less compared with their age and race matched female counterparts (4.6±1.2 hours), regardless of the weight, height and body surface. [38]

8. Concomitant drug administration:

Anticholinergic like atropine, propentheline-increase GRT and metoclopramide and cisapride-decrease GRT.

9. Disease state:

Gastric ulcer, diabetes, hypothyroidism increase GRT and hyperthyroidism, duodenal ulcers decrease GRT.

Different techniques of gastric retention:

Gastro retentive drug delivery systems are the systems which are retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs that are preferentially absorbed from upper GIT.

1. Floating Drug Delivery System:

The floating sustained release dosage forms present most of the characteristics of hydrophilic matrices and are known as ‘hydro dynamically balanced systems (‘HBS’) since they are able to maintain their low apparent density, while the polymer hydrates and builds a gelled barrier at the outer surface. They have a bulk density lower than gastric fluids and thus remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at a desired rate from the stomach. After the release of the drug, the residual system is emptied from the stomach. This results in an increase in the gastric retention time and a better control of fluctuations in the plasma drug concentration. The drug is released progressively from the swollen matrix, as in the case of conventional hydrophilic matrices. These forms are expected to remain buoyant (3- 4 hours) on the gastric contents without affecting the intrinsic rate of emptying because their bulk density is lower than that of the gastric contents. Among the different hydrocolloids recommended for floating form formulations, cellulose ether polymers are most popular, especially hydroxypropyl methylcellulose. Fatty material with a bulk density lower than one may be added to the formulation to decrease the water intake rate and increase buoyancy. [39, 40]

Floating drug delivery offers a number of applications for drugs having poor bioavailability because of narrow absorption window in the upper part of gastrointestinal tract. It retains the dosage form at the site of absorption and thus enhances the bioavailability. A gastric floating drug delivery system (GFDDS) is particularly useful for drugs that are primarily absorbed in the duodenum and stomach. The GFDDS is able to prolong the retention time of a dosage form in the stomach, thereby improving the oral bioavailability of the drug. [41] Floating systems are of two types: effervescent systems, depending on the generation of carbon dioxide gas upon contact with gastric fluids, and non-effervescent systems. The latter systems can be further divided into four sub-types, including hydro dynamically balanced systems, microporous compartment systems, alginate beads and hollow microspheres/microballons, super-porous hydrogels and magnetic systems.

(A) Effervescent systems:

These are matrix system prepared mainly using swellable polymers such as Methylcellulose and chitosan and various effervescent compounds, e.g. sodium bicarbonate, tartaric acid and citric acid. They are formulated in such a way that when in contact with the gastric contents, CO₂ is liberated and gets entrapped in swollen hydrocolloids, which provides buoyancy to the dosage forms. [42]

i. Gas generating systems:

These buoyant systems utilize matrices prepared with swellable polymers like methocel, polysaccharides like chitosan, effervescent components like sodium bicarbonate, citric acid and tartaric acid or chambers containing a liquid that gasifies at body temperature. The optimal stoichiometric ratio of citric acid and sodium bicarbonate for gas generation is reported to be 0.76:1. The common approach for preparing these systems involves resin beads loaded with bicarbonate and coated with ethyl cellulose. The coating, which is insoluble but permeable, allows permeation of water. Thus, carbon dioxide is released, causing the beads to float in the stomach.

Other approaches and materials that have been reported are highly swellable hydrocolloids and light mineral oils, a mixture of sodium alginate and sodium bicarbonate, multiple unit floating pills that generate carbon dioxide when ingested, floating minicapsules with a core of sodium bicarbonate, lactose and polyvinyl pyrrolidone coated with hydroxypropyl methylcellulose (HPMC) and floating systems based on ion exchange resin technology, etc. Excipients used most commonly in these systems include HPMC, polyacrylate polymers, polyvinyl acetate, Carbopol®, agar, sodium alginate, calcium chloride, polyethylene oxide and polycarbonates.

ii. Matrix Tablets

Single layer matrix tablet is prepared by incorporating bicarbonates in matrix forming hydrocolloid gelling agent like HPMC, chitosan, alginate or other polymers and drug. Bilayer tablet can also be prepared by gas generating matrix in one layer and second layer with drug for its SR effect. Floating capsules also prepared by incorporating such mixtures. [42]

Triple layer tablet also prepared having first swellable floating layer, second sustained release layer of 2 drugs (Metronidazole and Tetracycline) and third rapid dissolving layer of bismuth salt. This tablet is prepared as single dosage form for Triple Therapy of H.pylori.

(B) Non-effervescent system

Non-effervescent floating dosage forms use a gel forming or swellable cellulose type of hydrocolloids, polysaccharides, and matrix-forming polymers like polycarbonate, polyacrylate, polymethacrylate, and polystyrene. The formulation method includes a simple approach of thoroughly mixing the drug and the gel-forming hydrocolloid. After oral administration this dosage form swells in contact with gastric fluids and attains a bulk density of < 1. The air entrapped within the swollen matrix imparts buoyancy to the dosage form. The so formed swollen gel-like structure acts as a reservoir and allows sustained release of drug through the gelatinous mass. [43]

2. Hydrodynamically balanced systems:

Sheth and Tossounian first designated these ‘hydrodynamically balanced systems’. These systems contains drug with gel-forming hydrocolloids meant to remain buoyant on the stomach content. These are single-unit dosage form, containing one or more gel-forming hydrophilic polymers.[44] Hydroxypropyl methylcellulose (HPMC), hydroxethyl cellulose (HEC), hydroxypropyl cellulose (HPC), sodium carboxymethyl cellulose (NaCMC), polycarbophil, polyacrylate, polystyrene, agar, carrageenans or alginic acid are commonly used excipients to develop these systems.[45] The polymer is mixed with drugs and usually administered in hydrodynamically balanced system capsule. The capsule shell dissolves in contact with water and mixture swells to form a gelatinous barrier, which imparts buoyancy to dosage form in gastric juice for a long period.[46] Because, continuous erosion of the surface allows water penetration to the inner layers maintaining surface hydration and buoyancy to dosage form. Incorporation of fatty excipients gives low-density formulations reducing the erosion. Madopar LP®, based on the system was marketed during the 1980’s.

3. Microballoons / Hollow microspheres:

Microballoons / hollow microspheres loaded with drugs in their other polymer shelf were prepared by simple solvent evaporation or solvent diffusion evaporation methods to prolong the gastric retention time (GRT) of the dosage form. Commonly used polymers to develop these systems are polycarbonate, cellulose acetate, calcium alginate, Eudragit S, agar and low methoxylated pectin etc. Buoyancy and drug release from dosage form are dependent on quantity of polymers, the plasticizer polymer ratio and the solvent used for formulation. The microballoons floated continuously over the surface of an acidic dissolution media containing surfactant for >12 hours [47]. At present hollow microspheres are considered to be one of the most promising buoyant systems because they combine the advantages of multiple-unit system and good floating.

4. Alginate beads:

Talukdar and Fassihi recently developed a multiple-unit floating system based on cross-linked beads. They were made by using Ca²+ and low methoxylated pectin (anionic polysaccharide) or Ca²+ low methoxylated pectin and sodium alginate. In this approach, generally sodium alginate solution is dropped into aqueous solution of calcium chloride and causes the precipitation of calcium alginate. These beads are then separated and dried by air convection and freeze drying, leading to the formulation of a porous system, which can maintain a floating force for over 12 hrs. These beads improve gastric retention time (GRT) more than 5.5 hrs. [48] Microporous compartment system: This approach is based on the principle of the encapsulation of a drug reservoir inside a microporous compartment with pores along its top and bottom walls. The peripheral walls of the device were completely sealed to present any direct contact of the gastric surface with the undissolved drug. In the stomach the floatation chamber containing entrapped air causes the delivery system to float in the gastric fluid. Gastric fluid enters through the aperture, dissolves the drug and causes the dissolved drug for continuous transport across the intestine for drug absorption.

5. Bioadhesive:

Bio/mucoadhesive systems are those which bind to the gastric epithelial cell surface or mucin and serve as a potential means of extending the Gastro retention of drug delivery system (DDS) this approach involves the use of bioadhesive polymers, which can adhere to the epithelial surface in the stomach. The original concept of bioadhesive polymers as platforms for oral controlled drug delivery was to use these polymers to control and to prolong the GI transit of oral controlled delivery systems for all kinds of drugs. Whereas Bioadhesion has found interesting applications for other routes of administration (buccal, nasal, rectal and vaginal), it now seems that the controlling approach of GI transit has been abandoned before having shown any significant clinical outcome. [49]

According to in vivo results obtained in animals and in humans, it does not seem that mucoadhesive polymers are able to control and slow down significantly the GI transit of solid delivery systems. Attention should be paid to possible occurrence of local ulcerous side effects due to the intimate contact of the system with mucosa for prolonged periods of time. The continuous production of mucous by the gastric mucosa to replace the mucous that is lost through peristaltic contractions and the dilution of the stomach content also seem to limit the potential of mucoadhesion as a gastro retentive force. [50]

Table 3: Examples of gastro retentive drug delivery system with potential application

Sr.No	Drug	Dosage form	Remark	Reference
1	Alfuzosin hydrochloride	swellable and floatable composite delivery systems	Zero-order delivery	Quan Liu, 2008
2	Amoxicillin	intra-gastric floating in situ gelling system	controlled delivery of amoxicillin for the treatment of peptic ulcer	P.S. Rajinikanth, 2007
3	Theophylline	Floating tablets	gastro retentive and sustain release	C. Sauzet, 2009 (imp paper
4	Riboflavin	Expandable gastroretentive dosage form	increased gastric residence time	Iman S. Ahmed, 2007
5	Cefuroxime axetil	HBS Floating tablets	increase gastric residence time and thereby improve its bioavailability.	Govikari Koteshwar Rao, 2012
6	Riboflavin	Compressed collagen sponges (Expandable oblong tablets)	sustained release dosage forms	Rudiger Groninga, 2007
7	ciprofloxacin hydrochloride	effervescent floating matrix tablets	gastroretentive controlledrelease drug delivery system with swelling, floating, and adhesive properties.	Mina Ibrahim Tadros, 2010
8	Anhydrous theophylline	Floating multi-layer coated tablets based on gas formation	Good floating properties and sustained drug release	Srisagul Sungthongjeen, 2008
9	Diltiazem hydrochloride	multi-unit floating alginate (Alg) microspheres	sustained drug release	Ninan Ma, 2008
10	clarithromycin	Floating in situ gelling system	prolonged gastrointestinal residence time and enhanced stability	P.S. Rajinikanth, 2008
11	Rifampicin	Immediate release pellets	targeting its sustained release in the stomach	Swati Pund, 2011
12	l-dopa	hydrodynamically balanced systems (HBS) capsules	controlled release carrageenan–HPMC based dosage forms.	P. Doroz ynskia, 2011
13	Ofloxacin	Hydrodynamically balanced systems (HBSs) capsules	sustained drug release, increased mean residence time in g.i.t,.	Amit Kumar Nayak, 2011
14	5-aminosalicylic acid	enteric matrix tablet	Improved processing parameters and controlled release rate	Gavin P. Andrews, 2008
15	Ibuprofen	Multiple unit buoyant beads	prolonged drug release, increased bioavailability	Jadupati Malakar, 2012
16	Losartan	swelling/floating gastroretentive drug delivery	Improved systemic availability	Ray-Neng Chen, 2010
17	Metronidazole	chitosan-treated alginate beads	Improved processing parameters	R.A.H. Ishak et al., 2007
18	propranololHCl	Floatingtablet	Gastric residence time enhanced	Meka VenkataSrikanth, 2012
19	Repaglinide	Calcium silicate based microspheres	excellent buoyant ability and suitable drug release pattern	Sunil K. Jain, 2005

Table 4: Types of Gastroretentive systems

Sr.No.	Dosage forms	Drugs
1.	Floating microspheres	Aspirin, Griseofulvin, p-nitroaniline, Ibuprofen, Terfinadine and Tranilast
2.	Floating granules	Diclofenac sodium, Indomethacin and Prednisolone
3.	Films	Cinnarizine
4.	Floating Capsules	Chlordiazepoxide hydrogen chloride, Diazepam, Furosemide, Misoprostol, L-Dopa, Benserazide, Ursodeoxycholic acid and Pepstatin
5.	Floating tablets and Pills	Acetaminophen, Acetylsalicylic acid, Ampicillin, Amoxycillin trihydrate, Atenolol, Diltiazem, Fluorouracil, Isosorbide mononitrate, Para- aminobenzoic acid, Piretamide, Theophylline and Verapamil hydrochloride
6.	Colloidal gel forming FDDS	Ferrous sulphate
7.	Gas generating floating form	Ciprofloxacine
8.	Bilayer floating capsule	Misoprostol

Table 5: Marketed preparations of some drugs with GRDDS

Sr.No.	Drug	Brand name
1.	Diazepam Floating capsule	Valrelease®
2.	Benserazide and L-Dopa	Madopar®
4.	Aluminium – Magnesium antacid	Topalkan®
5.	Antacid preparation	Almagate Flot-Coat®
6.	Mixture of alginate	Liquid Gaviscone®
7.	Ferrous sulphate	Conviron®
8.	Ciprofloxacine	Cifran OD®
9.	Metformin HCl	Glucophage XRTM

CONCLUSION:

The criteria of factorial design are successfully implemented in case of Gastro-retentive drug delivery system. Most of the agents like sodium bicarbonate and tartaric acid have predominant effect on the floating lag time and is decreased with the increase in the ratio of polymer HPMC K4M and xanthan gum; along with increased drug release where as guar gum has retardant effect. The floating drug delivery is a promising approach to achieve in vitro buoyancy by using gel-forming polymers and gas-generating agent. These systems can provide zero order delivery. The unique features of these types of gastro retentive systems are the rapid swelling and floatation. This offers a great opportunity to the formulation scientists to develop and evaluate the variety of swelling and floating drug delivery systems for highly soluble drugs. The poor physico-chemical and pharmacological properties can be rendered by using this approach. In future, it would be possible to exploit the potential application of these systems for delivery of newly developed drugs which encompass difficulty in formulation and development.

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Received on 11.01.2016 Modified on 23.04.2016

Research J. Pharm. and Tech. 2016; 9(6):641-649

DOI: 10.5958/0974-360X.2016.00122.0