Site specific drug delivery:
A floating dosage form is a feasible approach especially for drugs like riboflavin and furosemide which have limited absorption sites in upper small intestine. The absorption of furosemide has been found to be site-specific, the stomach being the major
site of absorption, followed by the duodenum.
Monolithic floating dosage form for furosemide, could prolong the GRT, and increase its bioavailability. Bilayer floating capsule has been used to achieve local delivery of misoprostol at the gastric mucosa level. It is a synthetic prostaglandin E1analog approved and marketed in the US (as Cytotec®) for prevention of gastric ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs).
Basically it replenishes the GI-protective prostaglandins that are depleted by NSAIDs. Thus, the controlled, slow delivery of misoprostol to the stomach provides sufficient local therapeutic levels and limits the systemic and intestinal exposure to the drug. This reduces the side effects. The prolonged gastric availability from a site directed delivery system may also reduce the dosing frequency.
Sustained Drug Delivery:
Drug absorption from oral CR dosage forms is often limited by the short GRT available for absorption.
However, HBS type dosage forms can remain in the stomach for several hours and, therefore, significantly prolong the GRT of numerous drugs.
These systems have a bulk density of less than 1 as a result of which they can float on the gastric contents.
These special dosage forms are light, relatively large in size and do not easily pass through the pylorus.
A prolonged GRT is not responsible for the slow absorption of a lipophilic drug such as isradipine that has been achieved with a ‘floating’ modified-release capsule. This is because the major portion of drug release modified- release capsule took place in the colon, rather than in the stomach. However, the assumed prolongation in the GRT is postulated to cause sustained drug-release behavior. The administration of diltiazem floating tablets twice a day may be more effective compared to normal tablets in controlling the blood pressure of hypertensive patients. The duration of hypotensive effects was longer with floating tablets than that with normal ones. Madopar® HBS, has been shown to release levodopa for up to 8 h invitro, whereas the release from the standard Madopar® formulation is essentially complete in less than 30 min. Madopar®
HBS behaves as a controlled / slow-release formulation of L-dopa and benserazide.
Sustained release floating capsules of nicardipine hydrochloride were developed and were evaluated.
56 Plasma concentration time curves showed a longer duration for administration (16 hours) in the sustained release floating capsules as compared with conventional MICARD capsules (8 hours). (Brahma N 2000)
Absorption Enhancement:
Drugs that have poor bioavailability because of site specific absorption from the upper part of the gastrointestinal tract are potential candidates to be formulated as floating drug delivery systems, thereby maximizing their absorption. (Archana M 2008)
Recent Advances:
Multi-unit floating alginate (Alg) microspheres using calcium carbonate were developed by Ninan Ma et al. To enhance the drug encapsulation efficiency and delay the drug release chitosan (Cs) was added. The gastrointestinal transit of the optimized floating sustained release microspheres was compared with that of the non-floating system manufactured from identical material using the technique of gamma-scintigraphy. A prolonged gastric retention time of over 5 h was achieved in the volunteers for the optimized coating floating microspheres. (Amit K 2011)
GRDDS, comprised mainly of floating, bioadhesive, and swellable systems, have emerged as an efficient means of enhancing the bioavailability and controlled delivery of drugs that exhibit an absorption window.
The recent developments include the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems by prolonging the gastric emptying
time of the dosage form. These systems not only provide controlled release of the drug for a prolonged period, but also present the drug in an absorbable form at regions of optimal absorption. These systems achieve this by retaining the dosage form in the gastric region, from where the drug is presented at the absorption window. This ensures maximal absorption of the drug for the desired period. The effect of GI physiology on drug delivery and the increasing sophistication of delivery technology will ensure the development of an increasing number of GRDDS to optimize delivery of drug molecules that exhibit regional variability in intestinal absorption. A novel floating controlled-release drug delivery system increases the gastric retention time of the dosage form and controls drug release. Floating matrix tablets are designed to prolong the gastric residence time after oral administration, at a particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability.
Marketed Products of GRDDS
57
Brand name Drug Company & Country Remarks
Modapar® Levodopa (100 mg), Benserazide (25 mg)
Roche Products, USA Floating CR Capsule
Valrelease® Diazepam (15 mg) Hoffmann- LaRoche, USA Floating capsule Liquid Gavison® Al hydroxide (95 mg),
Mg carbonate (358 mg)
Glaxo Smith Kline, India Effervescent floating liquid alginate preparation
Topalkan® Al-Mg antacid Pierre Fabre Drug,
France
Floating liquid Alginate preparation
Conviron® Ferrous sulphate Ranbaxy, India Colloidal gel forming FDDS
Cifran OD® Ciprofloxacin (1 gm) Ranbaxy, India Gas-generating floating tablet
Oflin OD® Ofloxacin (400mg) Ranbaxy, India Gas generating floating tablet
Cytotec® Misoprostal (100 mcg/200 mcg) Pharmacia, USA Bilayer floating capsule
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