INTRODUCTION:

Administering a drug via oral route is the most favourable and safest way to deliver a drug due to its cost effectiveness, easy administration, fabrication and better patient compliance.^1-5 Drug having shorter half life gets out from systemic circulation very fast and constant administration of dose is essential to achieve desired therapeutic effect. Problems related to traditional conventional forms can be reduced by designing and formulating oral sustained-controlled dosage forms that allow the slow release of drug in GI Tract and maintenance of effective drug concentration in systemic circulation for prolonged period. For continuous supply to drug to absorption sites in GI tract can be achieved by administration of drug through a drug delivery system which will be retained in stomach and drug will start releasing from it in controlled manner.⁶

Since last 30 years new devices and technologies are being developed and designed to retain in the upper part of GI tract for localized and more effective drug delivery and it includes various approaches like floating systems, expanding systems, swelling systems, bioadhesive systems and low density systems etc.⁷Development of oral controlled release system is a challenging task for researchers and persons working in R&D, Formulation development for targeted delivery of drug in the areas of GI Tract. Main reason behind developing controlled drug delivery and increased interest in developments of new system is to keep drug plasma levels within therapeutic window for prolonged period that ensures sustained therapeutic effectiveness.⁸

GRDDS are designed to increase the gastric-retention time of drugs that are:

1. Poorly soluble in high pH range.

2. Having Narrow absorption window in GIT.

3. Not stable in Intestinal Environment.

4. Locally active in the stomach.^9-12

NEED FOR GRDDS:

Conventional dosage forms are most commonly used to treat various diseases but due to major drawback associated with them are, they are not site-specific; some drugs are absorbed at specific site only or require release at targeted site to obtain maximum effect and to overcome these problems GRDDS is designed to achieve drug delivery at specific sites like stomach, intestine, colon and duodenum in controlled manner.¹⁶

Table No.1: Merits and Demerits of GRDDS^13-15

Merits	Demerits
Improved Bioavailability	Not suitable for drugs causing GI lesions and irritating gastric mucosa
Improved Therapeutic effectiveness	Not suitable for unstable drugs that are less soluble in highly acidic and basic conditions
Reduced dose and dosing frequency	Dosage form has to cross gastric conditions with affecting its properties, which is hard to achieve
Constant therapeutic levels for longer period are maintained	For Drugs that are absorbed through Gastro intestinal tract, GRDDS have No significant advantage over conventional dosage form
Reduced fluctuation in drug levels in blood
Prolonged GI Transit time due to retention in stomach
Drugs having low bioavailability in acidic pH are absorbed well
Less side effects
delivery of drug to targeted site
Safest route and cost effective

Physiology of Stomach:

Gastro- intestinal tract is a nine meter long tube passing through center of the body starting from mouth and ending at anus and it covers throat, oesophagus, stomach, small and large intestine having same wall structure throughout GI tract from oesophagus with minute variations in each region. Stomach is part which is there for purpose of mixing and storage and antrum region have function of grinding and mixing of gastric juices.

The inter-digestive movement patters is known as “Migrating motor complex” and it is divided in cycles, each of that lasts for 90 to 120 minutes and comprise of 4 phases:

· Phase - I: Also known as basal phase which lasts for 40 to 60 minutes with rare contractions.

· Phase - II Also known as pre-burst phase which lasts for 40 to 60 minutes with intermittent potential and contraction.

· Phase - III: Also known as burst phase which lasts for 4 to 6 minutes with intense and regular contraction for small period due to which un-digestive food passes from stomach to intestine

· Phase - IV: Lasting for 0 to 5 minutes and it takes place between III and I phase for two successive cycles.^17-18

Figure No. 1: Physiology of stomach¹⁹

Potential Drug Candidates for Grdds²⁰

1. Drugs which are locally active in stomach region (Example: Antacid)

2. Drugs with narrow absorption window in GI tract. (Example: L-DOPA, PABA)

3. Drugs which are unstable in colon and intestine. (Example: Captopril)

4. Drugs disturbing microbial flora of colon. (Example: Antibiotic acting against H.Pylori)

5. Drugs that are less soluble at high pH (Exampl: Diazepam)

Drug Candidates that are not Suitable for Grdds^21-25

1. Poorly soluble drugs. (Example: Phenytion)

2. Drugs those are unstable in GI environment. (Example: Erythromycin)

3. Drugs used for site specific drug delivery in colon. (Exapmle: Corticosteroids)

Factors Influencing Gastric Retention^26-33

· Density of Dosage form

· Size and shape of Dosage form

· Nature of diet

· Intake of food

· Age

· Sex

· Disease condition

· Body pos

Table No.2: Polymers and other materials used in Formulation of Grdds^34-44

Sr. No	Category	Materials (Examples)
1	Polymers	HPMC, Calcium alginate, Eudragit RL, Polyethylene glycol etc.
2	Inert fatty materials	Bees wax, fatty acid etc.
3	Effervescent compounds	Tartaric acid, citric acid, sodium bicarbonate etc.
4	Release accelerants	Mannitol, lactose etc.
5	Release retardants	Magnesium stearate, Talc, etc.
6	Agent that increase Buoyancy agents Buoyancy increasing	Ethyl cellulose
7	Materials having low density	Propylene foam powder

Evaluation of Grdds:

Numerous parameters are needed to be evaluated when solid dosage forms are concerned such as Flow properties, hardness, friability, content uniformity, and thickness of tablet.^61-65

DSC, Drug entrapment, Particle size analysis suing SEM, floe properties and mechanical properties are also determined when multi-particulate systems are involved and there are some tests like Floating ability, swelling index, floating time, buoyancy lag time and In-Vitro drug release are also done in parallel in gastric fluids at 37ºC temperature.^66-72

In-vivo floating properties are determined by performing X-ray photography of micro-particles containing BaSO4 in stomach. Some radio-opaque materials are also incorporated in solid dosage form to make them visualize by X-Rays in GI tract to check its Transit period. Similarly Scintigraphy is used to obtain the images and Gastroscopy/endoscopy is used to check prolongation in stomach for evaluation of GRDDS.^73-78

CONCLUSION:

This article is an attempt to compile Important and valuable information related to all aspects of GRDDS and it will serve as a valuable source of information for all the researchers and scientist that are involved in research on GRDDS and for exploring new insights into it.

ACKNOWLEDGEMENT:

Authors would like to thank Management and Dean, School of pharmacy, Madhyanchal Professional University for their constant support.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

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Received on 05.12.2020 Modified on 21.04.2021

Research J. Pharm.and Tech 2022; 15(3):1343-1347.

DOI: 10.52711/0974-360X.2022.00224