MODERN STATE OF CREATION, PRODUCTION AND RESEARCH OF DRUGS Message 21. Characteristic of creation and research process of flotating drug delivery system

Abstract

MODERN STATE OFCREATION, PRODUCTION AND RESEARCH OF DRUGS

Message 21. Characteristic of creation and research process of flotating drug delivery system

N. P. Darzuli, M. B. Demchuk, T. A. Hroshovyi

I. Horbachevsky Ternopil State Medical University

Introduction. Floating drug delivery systems have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. Floating drug delivery systems can be divided into non effervescent and gasgenerating (effervescent) system.

Effervescent systems the main mechanism involved in this system is the production of carbon-dioxide gas due to reaction between sodium bicarbonate, citric acid or tartaric acid. The gas produced results in the reduction of density of the system thereby making it to float on the gastric fluids. These systems are further classified as volatile liquid containing systems, matrix tablets, gas generating systems, floating capsules, floating pills, floating systems with ion exchange resins.

Matrix tablets may be formulated as a single layer matrix tablet by incorporating bicarbonates in matrix forming hydocolloid gelling agent or a bilayer matrix tablet with gas generating matrix as one layer and drug being the second layer. It can also be formulated as triple layer matrix tablet with gas generating matrix as one layer and 2 drug layers.

Gas generating systems utilise effervescent compounds like sodium bicarbonate, citric acid and tartaric acid. It is further divided as follows.

Floating capsules prepared  by formulating mixture of sodium bicarbonate and sodium alginate. On exposure to acidic environment, carbon dioxide gas is generated which is trapped in the hydrating gel network and makes the system to float.

Floating pills a type of sustained release formulations which are basically multiple unit type of dosage forms. The sustained release pill is surrounded by two layers. Outer layer consists of swellable membrane and the inner layer consists of effervescent agents. The system swells due to swellable membrane and then sinks. Due to presence of effervescent agents, CO2 is released and the system floats.

Floating systems with ion exchange resins the most common approach for formulating these systems involves resin beads loaded with bicarbonate. This is then coated with ethyl cellulose which is usually insoluble but permeable to water. This causes carbondioxide to release and the system to float.

Non- Effervescent systems a type of floating gastroretentive drug delivery systems in which gel forming hydrocolloids, polysaccharides and matrix forming polymers like polycarbonate, polystyrene, polymethacrylateetc are used. These are further  classified as hydrodynamically balanced systems, microballoons / hollow microspheres, alginate beads, layered tablets.

Hydrodynamically balanced systems contain drug with gel forming hydrocolloids formulated into a single unit dosage form. Upon contact with gastric fluids, the hydrocolloids swell to form a gel barrier which facilitates the system to remain buoyant in the stomach.

Microballoons / hollow microspheres  contain outer polymer shell loaded with drug. The outer polymer shell is made up of polymers like polycarbonate, cellulose acetate, calcium alginate, agar, etc. Buoyancy lag time and drug release from the system is dependent on the quantity of polymers used in the formulation. These are prepared by emulsion-solvent diffusion method.

Alginate beads formulated using calcium and low methoxylated pectin or calcium low methoxylated pectin and sodium alginate. In this type, sodium alginate solution is added to aqueous solution of calcium chloride which causes precipitation of calcium alginate (beads). These beads are then separated and dried by air convection and freeze dried. This results in the formation of aporoussystem which remains buoyant in the stomach.

 Layered tablets may be of single layer or double layered. Single layered floating tablets, this type of tablets contain drug mixed with gel forming hydrocolloids and other excipients. Upon contact with gastric fluids, the hydrocolloids swell and maintain bulk density less than one and hence remain buoyant in the stomach. Double layered floating tablets this type of tablets contain two layers, one of which is immediate releasing layer and the other is sustained release layer containing drug and hydrocolloids which remains in the stomach for a prolonged period.

Conclusions. The basic requirements and approaches to the development of flotating drug delivery systems and examples to obtain tablets that can be kept for a long time in the stomach has been considered.

References

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