Thursday, December 16, 2010
Floating dosage forms: An overview
Floating dosage forms: An overview
Drug delivery systems are used for maximizing therapeutic index of the drug and reduction in side effects due to site-specific drug delivery. With the recent developments and advances in pharmaceuticals, frequently taken medicaments are incorporated in a single unit dosage form. This reduces the frequency of administration of medicament to the patient. The real challenge in the development of a controlled drug delivery system is not just to sustain the drug release but also to prolong the presence of the dosage form in the stomach or the upper small intestine until all the drug is completely released in the desired period of time. The residence of a drug delivery system in the upper part of the gastrointestinal tract (GIT) can be accomplished by several drug delivery systems, such as intragastric floating systems, swelling and expandable systems, bioadhesive systems, modified shape systems, high-density systems, [ delayed gastric-emptying systems [and low-density super porous systems. This review deals with floating dosage forms, an oral novel drug delivery system.
In general, the drug release is governed by various polymers, which are used in the formulation. These polymers entrap the drug material in the matrix form or form a membranous sheath around the drug. The polymer in either case controls the release rate of drug by diffusion or by erosion method. Such drug delivery systems are termed as controlled drug delivery systems, which release the drug(s) with a predictable kinetics. 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. Excipients used most commonly in these systems include HPMC, polyacrylate polymers, polyvinyl acetate, polyethylene glycol (PEG)-6000, Carbopol, agar, sodium alginate, calcium chloride, polyethylene oxide and polycarbonates. Drugs used in the formulation of floating dosage forms.
The oral dosage forms taken orally are very much affected by the gastric physiology. As it is the gastric residence time (GRT), which decides the retention time of oral dosage form in GIT, the gastric emptying (GE) of liquids in the fasted state is a function of the volume administered. The normal GE t½ is 46.5 ± 5.5 min. This sets an approximately 10 h limit for the delivery of drugs absorbed solely from the small intestine region. The various factors affecting GE include age, diseased state and diet. Normal aging is associated with various changes in gastrointestinal motility. The important factor is the impact of various age-related diseases on gastrointestinal motility in elderly patients; for example, long-standing diabetes mellitus may reduce GE in about 50%, depression significantly prolongs whole gut transit time, hypothyroidism may prolong orocecal transit time and chronic renal failure is associated with impaired GE. (Gastro intestinal transit time) In addition, various frequently used drugs in an elderly patients cause disordered gastrointestinal motility. These drugs include anticholinergics, especially antidepressants with an anticholinergic effect, opioid analgesics and calcium antagonists. Delayed GE or gastrointestinal symptoms occur in 30%-50% of patients with diabetes as well as in chronic liver diseases. High electrolyte content tends to decrease GE.Glucose supplementation accelerates GE of glucose, viscous polysaccharides show delayed GE and slow transit through the small bowel. The GE is significantly slow during dehydration and at times the GE is very rapid as with liquid diet, emotional stress and exercise. Thus, oral controlled release drug delivery systems have limited use in the gastrointestinal controlled administration of drugs if the system cannot remain in the vicinity of the absorption site for lifetime of the drug delivery. The transit time for the mouth to the anus varies with each individual. Oral delivery for 24 h is possible for many drugs; however, the substance must be adequately absorbed throughout the whole GIT. A significant obstacle may arise if there is a narrow window for drug absorption in the GIT or if a stability problem exists in GI fluids or the drug is poorly soluble in the intestine or acts locally in the stomach.Taking these factors into consideration, investigators formulated a novel drug delivery system for controlled drug delivery at the stomach level, termed as floating tablets or Hydrodynamically Balanced Systems (HBS) or gastroretentive drug delivery systems to prolong the residence of the dosage forms in the stomach or somewhere in the upper small intestine until all the drug is released for the desired period. Gastroretentive systems can remain in the gastric region for several hours, and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestine. Gastroretention helps provide better availability of new products with new therapeutic possibilities and substantial benefits for patients.