Gastroretentive Drug Delivery System - An Overview

In recent years scientific and technological advancements have been made in the research and development of controlled release oral drug delivery systems by overcoming physiological adversities like short gastric residence times and unpredictable gastric emptying times. Gastroretentive 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.

The whole 16 pages article is available for download here.

Different approaches for gastroretentive dosage forms include floating, raft, expanding or swelling, bioadhesive or mucoadhesive and high/low-density systems. The oral controlled drug delivery systems (DDS) should be primarily aimed to achieving more predictable and increased bioavailability of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, useful for drugs acting locally in the GIT, drugs which are poorly soluble and unstable in intestinal fluids. These systems are advantageous in improving GIT absorption of drug with CR due to specific site absorption limitations. Among the various gastro retentive systems, gastric floating drug delivery systems (GFDDS) offer numerous advantages over the gastric retentive systems. These systems have a density lower than the 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.

INTRODUCTION

The oral route is considered as the most promising route of drug delivery. Effective oral drug delivery may depend upon the factors such as gastric emptying process, gastrointestinal transit time of dosage form, drug release from the dosage form and site of absorption of drugs. Most of the oral dosage forms possess several physiological limitations such as variable gastrointestinal transit, because of variable gastric emptying  leading to non-uniform absorption profiles, incomplete drug release and shorter residence time of the dosage form in the stomach. This leads to incomplete absorption of drugs having absorption window especially in the upper part of the small intestine, as once the drug passes down the absorption site, the remaining quantity goes unabsorbed. The gastric emptying of dosage forms in humans is affected by several factors because of which wide inter- and intra-subject variations are observed ¹. Since many drugs are well absorbed in the upper part of the gastrointestinal tract, such high variability may lead to non-uniform absorption and makes the bioavailability unpredictable. Hence a beneficial delivery system would be one which possesses the ability to control and prolong the gastric emptying time and can deliver drugs in higher concentrations to the absorption site (i.e. upper part of the small intestine).

Floating Drug Delivery Systems (FDDS)  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 of the drug, the residual system is emptied from the stomach. This results in an increase in the GRT and a better control of fluctuations in the plasma drug concentrations.

The identification of new diseases and the resistance shown towards the existing drugs called for the introduction of new therapeutic molecules. In response, a large number of chemical entities have been introduced, of which some have absorption all over the gastrointestinal tract (GIT), some have absorption windows (i.e. absorption sites, especially the upper part of the small intestine) and some drugs have poor solubility in intestinal media. The drugs belonging to the second and third categories, and the drugs which are required for local action in the stomach, require a specialized delivery system. All the above requirements can be met and effective delivery of the drugs to the absorption window, for local action and for the treatment of gastric disorders such as gastro-esophageal reflux, can be achieved by floating drug delivery systems (FDDS).

To date, a number of FDDS involving various technologies, carrying their own advantages and limitations were developed such as, single and multiple unit hydro dynamically balanced systems (HBS), single and multiple unit gas generating systems, hollow microspheres and raft forming systems².

The hydrodynamic balanced system (HBS) also called Floating drug delivery system (FDDS) is an oral dosage form (capsule or tablet) designed to prolong the residence time of the dosage form within the GIT. It is a formulation of a drug with gel forming hydrocolloids meant to remain buoyant in the stomach contents. Drug dissolution and release from the dosage form retained in the stomach fluids occur at the pH of the stomach under fairly controlled conditions3. The retentive characteristics of the dosage form are not significant for the drugs that:

1)      Are insoluble in intestinal fluids

2)      Act locally

3)      Exhibit site-specific absorption.

            However, the system can be used for most of the drugs where controlled (sustained) release of the dosage form is desired by the oral route.

The formulation of the dosage form must comply with three major criteria for HBS.

1)   It must have sufficient structure to form a cohesive gel barrier.

2)   It must maintain an overall specific gravity less than that of gastric content.

3)   It should dissolve slowly enough to serve as a "Reservoir" for the delivery system.

Floating systems are one of the important categories of drug delivery systems with gastric retentive behavior. Drugs that could take advantage of gastric retention include:  furosemide, cyclosporine, allopurinol ciprofloxacin and metformin. Drugs whose solubility is less in the higher pH of the small intestine than the stomach (e.g. chlordiazepoxide and cinnarizine, the drugs prone for degradation in the intestinal pH (e.g. captopril), and the drugs for local action in the stomach (e.g. misoprostol) can be delivered in the form of dosage forms with gastric retention. Antibiotics, catecholamines, sedative, analgesics, anticonvulsants, muscle relaxants, antihypertensive and vitamins can be administered in HBS dosage form.^{4, 5,6,7,8}

Drugs reported to be used in the formulation of floating dosage forms are:

Chlorpheniraminemaleate,Theophylline,Furosemide,Ciprofolxacin,Pentoxyfillin, Captopril,Acetylsalicylicacid,Nimodipine,Amoxycillintrihydrate, VerapamilHCl, Isosorbidedinitrate, Sotalol, Atenolol, Isosorbidemononitrate, Acetaminophen, Ampicillin, Cinnarazine, Diltiazem, Florouracil, Piretanide,  Prednisolone, Riboflavin- 5′Phosphate,

Excipients used most commonly in these systems include HPMC, polyacrylate polymers, polyvinyl acetate, Carbopol, agar, sodium alginate, calcium chloride, polyethylene oxide and polycarbonates.  

The whole 16 pages article is available for download here.