Oral controlled release dosage forms (CRDF) have been extensively used to improve therapy of many important medications. The design of oral controlled drug delivery systems (CDDS) should primarily be aimed at achieving more predictable and increased bioavailability of drugs. However, the developmental process is precluded by several physiological difficulties, such as inability to restrain and locate the CDDS within desired regions of gastrointestinal tract (GIT) due to the variable gastric emptying and motility. The variability may lead to unpredictable time for peak plasma levels and bioavailability. Therefore, the CRDF approaches has not been suitable for a variety of important drugs, characterized by a narrow absorption window in the upper part of the GIT, i.e. stomach and small intestine, which is due to relatively short transit time of the dosage form in these anatomical segments. Thus within a short period (less than 6 hours), the CRDF of such drugs leave the upper part of GIT and reaches to the non-absorbing distal segment, eventually resulting in a short absorption phase accompanied with lesser bioavailability.
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Invariably, conventional dosage forms do not maintain the drug blood levels within the therapeutic range for an extended period of time. To achieve the same, a drug may be administered repeatedly using a fixed dosing interval. This causes several potential problems like saw tooth kinetics characterized by large peaks and troughs in the drug concentration-time curve (Figure 1.)
Figure 1: Plasma level profiles following conventional and controlled release dosing
The relatively brief gastric emptying time in humans normally averages 2 to 3 hours. through the major absorption zone (stomach or upper part of the intestine), which can result in incomplete drug release from the drug delivery system leading to diminished efficacy of the administered dose. Thus, placement of the drug delivery system in a specific region of the GIT offers numerous advantages, especially to the drugs having narrow absorption window in GIT, primary absorption in the stomach, stability problem in intestine, poor solubility at alkaline pH, local activity in stomach and property to degrade in colon. Compounding the drugs with narrow absorption window in a unique pharmaceutical dosage form, which prolongs the gastric residence time would enable an extended absorption phase of these drugs.
One of the most feasible approaches for achieving a prolonged and predictable drug delivery profiles in the GIT is to control the gastric residence time, using gastro-retentive dosage forms (GRDF). GRDF are the drug delivery systems that are designed to be retained in the stomach for a prolonged time and release their active materials and thereby enable sustained input of the drug to the upper part of the GIT. This technology has generated enormous attention over the last few decades owing to its potential application to improve the oral delivery of some important drugs for which prolonged retention in the upper GIT can greatly improve their oral bioavailability and/or their therapeutic outcome.
Figure 2: Comparison of conventional dosage form and gastro retentive dosage form
In the last three decades various attempts have been made to develop a novel and efficient gastro-retentive dosage forms which can retain in the stomach for an extended period of time in a predetermined manner. This can be achieved by improving scientific and technological advancement to overcome physiological problems like pH of the stomach, motility and gastric emptying time by altering physiological and formulation variables. Many approaches are utilized in the development of gastric retention drug delivery systems viz., floating systems, swelling, expanding, high density, super porous hydrogels, bioadhesive, modified shape systems, ion exchange resin and by the simultaneous administration of pharmacological agents that delay gastric emptying. By utilizing one of these techniques it is possible to deliver drugs that have narrow absorption window.
From the formulation and technological point of view, the floating drug delivery system (FDDS) is considerably easy and logical approach in the development of GRDF. Floating drug delivery system float on the gastric fluid only when it has density less than that of gastric fluids, i.e. <1g/cm3. Usually, floating formulations are prepared from hydrophilic matrices that either have a density lower than one or their density drops below one after immersion in the gastric fluids owing to swelling. More sophisticated devices are developed later and involved the use of various film coating techniques, incorporation of a floating chamber that is filled with harmless gas, or a liquid that gasifies at body temperature. These systems are often called hydro-dynamically balanced system (HBS) as they can maintain low density and keep floating even after hydrating. This system provides several advantages as prolonged gastric retention of drugs, improves bioavailability, reduces drug wastage and improves solubility for drugs that are less soluble in alkaline pH environment and provides local drug delivery to the stomach and proximal small intestine.
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Basic physiology of stomach: (Tortora G., 2006; Anne Waugh, 1996)
The stomach is a 'J' shaped enlargement of the GI tract directly inferior to the diaphragm in the epigastric, umbilical and left hypochondria regions of the abdomen. The stomach connects the esophagus to the duodenum, the first part of the small intestine. Anatomy of stomach is shown in Figure 3.
Figure 3: Anatomy of stomach
The stomach lies between the esophagus (proximally) and the duodenum (distally). It varies widely in size and shape depending on the person, the food content, and the posture of the body. It is J-shaped normally and the pyloric part lies horizontally or ascends to meet the proximal part of the duodenum.
Figure 4: Structure of the stomach
Anatomically the stomach is divided into 3 regions:
Fundus: The superior part of the stomach, this lies above the imaginary horizontal plane passing through the cardiac orifice.
Body: This lies between the fundus and the antrum, and it is the largest part of the stomach.
Antrum: This lies in the imaginary transpyloric plane and to the right of the angular notch. It joins the pyloric canal on its right.
The main function of fundus and body is storage whereas that of antrum is mixing or grinding. The fundus adjusts to the increased volume during eating by relaxation of the fundus muscle fibers. The fundus also exerts a steady pressure on the gastric contents, pressing them towards the distal stomach. To pass through the pyloric valve into the small intestine, particles should be of the order of 1 to 2 mm. The antrum does this grinding. The stomach has limitation of short residence time.
GASTRIC MOTILITY: ( Jain N. K., 2008)
The pattern of motility is distinct in fasted and fed states. During the fasting state an inter digestive series of electrical events takes place, which cycle both through stomach and intestine every 2 to 3 hrs. This is called the interdigestive myloelectric cycle or migrating myloelectric cycle (MMC), which is divided into following 4 phases.
Figure 5: Motility Patterns of the GIT in the Fasted State
Phase I (basal): Lasts for 30 to 60 minutes. With rare contractions and is characterized by a lack of secretary, electrical, and contractile activity.
Phase II (preburst): Lasts for 20 to 40 minutes. with intermittent action potential and contractions
Phase III (burst): Lasts for 10 to 20 minutes. Includes intense and regular contractions. It is due to this wave that all undigested material is swept out of the stomach down to the small intestine. It is also known as housekeeper wave.
Phase IV: Lasts for 0 to 5 minutes.
After the ingestion of a mixed meal, the pattern of contractions changes from fasted to fed state. It comprises continuous contractions as in phase II of fasted state. These contractions result in reducing the size of food particles (<1mm), which are propelled toward pylorus. During fed state onset of MMC is delayed resulting in slowdown of gastric emptying rate.
Gastric emptying: ( Jain N. K., 2008)
It can be anticipated that, depending upon the physiological state of subject and design of pharmaceutical formulation, the emptying process last from a few minute to 12 hours. Furthermore the relatively brief gastric emptying time in humans which normally averages 2 to 3 hours through the major absorption zone (stomach or upper part of intestine). Particle size and feeding state strongly affect the residence time of particles in the stomach. Some other factors affecting gastric emptying are type of meal and its caloric content, volume, viscosity and co-administered drugs. The rate of gastric emptying primarily depends on the caloric contents of the ingested meal. It does not differ for proteins, fats, and carbohydrates as long as their caloric content is the same. Generally an increase in acidity, osmolarity and caloric value slows down gastric emptying. Stress increases gastric emptying rate whereas depression slows it down. Females have a slower gastric emptying rate than males. Age and obesity also affect gastric emptying. Gastric emptying of dosage forms is different in fasted and fed conditions.
Table 1: Transit time of various dosage forms across the segments of the
Transit time (hours)
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Factors affecting gastric emptying time: (Vyas S., 2002; Bandyopadhyay A.K., 2008)
The resting volume of stomach is about 25 to 52 ml. This volume is important for dissolution of dosage forms. As the volume is large, emptying is faster. Gastric emptying of small volumes like 100 ml or less is governed by MMC cycle whereas large volumes of liquids like 200 ml or more are emptied out immediately after administration. Fluids at body temperature leave the stomach more rapidly than either warmer or colder fluids.
Stress conditions increases gastric emptying rate whereas depression slows down gastric emptying time. Generally females have slower gastric emptying rate than males. Age and obesity also affect gastric emptying.
Presence of Food:
Gastric emptying time differs in fasted state and in fed state. The caloric value of food affects the gastric emptying time.
Acids, pepsin, gastrin, mucus and other enzymes are the secretions of stomach. Normal adults produce a basal secretion upto 60 ml with approximately 4 millimoles of hydrogen ions every hour.
Factors affecting gastric residence time of dosage form:
(Vyas S., 2002; Bandyopadhyay A.K., 2008)
Gastric residence time increases if the density of the dosage form is less than the gastric contents (<1.004 gm/ml).
Size and shape:
Small-size tablets leave the stomach during the digestive phase while the large size tablets are emptied during the housekeeping waves.
Fed or unfed state:
Under fasting conditions, the GI motility is characterized by periods of MMC that occurs every 1.5 to 2 hours. The MMC sweeps undigested material from the stomach and if the timing of administration of the formulation coincides with that of the MMC, the gastric residence time of the unit can be expected to be very short. However, in the fed state, MMC is delayed and gastric residence time is considerably longer.
Frequency of feed:
The gastric residence time can be increased by over 400 minutes when successive meals are given compared with a single meal due to the low frequency of MMC.
Gastric residence time can vary between supine and upright ambulatory state of the patients.
Concomitant drug administration:
Anticholinergics like atropine and propentheline, opioids like codeine and prokinetic agents like metoclopromide and cisapride affects the GRT when administered together.
Diabetes and Crohn's disease also affects gastric residence time.
Formulation approaches for gastro retentive drug delivery systems (GRDDS):
(Garg R., 2008)
There are several formulation approaches used for designing GRDDS. These include Swelling and Expanding system, which are retained in the gastric region due to their large size gained after swelling. Floating system are retained in the gastric region due to their floating ability on the gastric fluid. The floating system is further divided into single unit system such as floating tablets and multiparticulate systems such as floating microspheres, which offer more advantages as compared to single unit system. The floating system is further divided into effervescent and non-effervescent floating system based on their mechanism of floating. Bioadhesive systems adhere to the gastric mucosa due to which they are retained in the gastric region. High density system are retained due to their increased density then the gastric fluid. Beside this, passage delaying food as well as drugs can be administered simultaneously to retain the dosage form in the gastric region.
The flowchart shows the various approaches used to retain the dosage forms in the gastric region.
Swelling and Floating System Bioadhesive Systems High-Density Expanding Systems Systems
Single Unit Systems Multiparticulate Systems
Effervescent Non-Effervescent Effervescent Non- Effervescent
Gas generating Low density polymers Microparticles Waxy Microparticles
excipients in gel (Hydrophilic & Microballons Alginate beads
forming polymers hydrophobic) Pellets, Beads Foam powder
Figure 6: Flowchart enlisting various approaches used for designing FDDS
Swelling and expanding systems:
Swelling type dosage forms are such that after swallowing, these products swell to an extent that prevents their exit from the stomach through the pylorus. As a result, the dosage form is retained in the stomach for a long period of time. These systems may be referred to as 'plug type' systems since they exhibit tendency to remain lodged at the pyloric sphincter.
Floating system (low density approach):
These systems are also known as hydro-dynamically balanced systems. (HBS/FDDS) They have a bulk density lower than gastric fluid, i.e. their bulk density is less than one. The specific gravity of gastric fluid is approximately 1.004 to 1.010 g/cm3 and thus the FDDS remains 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 system. After the release of the drug the residual system is emptied from the stomach.
They are used to localize a delivery device within the lumen and cavity of the body to enhance the drug absorption process in a site-specific manner. It makes use of bioadhesive polymers. These polymers tend to form hydrogen and electrostatic bonds at the mucus polymer boundary.
High density systems:
High density formulations include coated pellets that have density greater than that of stomach contents. (>1.004g/cm3) This is accomplished by coating the drug with heavy inert materials such as barium sulfate, titanium dioxide, iron powder or oxide. The weighted pellet can then be covered with a diffusion-controlling polymer membrane.
Modified shape systems:
These are non-disintegrating geometric shapes molded from silastic elastomer or extruded from polyethylene blends which extend the gastric residence time depending on size and shape of the dosage form
Use of other delayed gastric emptying devices:
It includes feeding of indigestible polymers or fatty acid salts that change the motility pattern of the stomach to a fed state, thereby decreasing the gastric emptying rate and permitting considerable prolongation of drug release.
Osmotic regulated system:
It is comprised of an osmotic pressure controlled drug delivery device and an inflatable floating support in a bioerodible capsule. In the stomach the capsule quickly disintegrates to release the intragastric osmotically controlled drug delivery device. The inflatable support inside forms a deformable hollow polymeric bag that contains a liquid that gasifies at body temperature to inflate the bag. The osmotic pressure controlled drug delivery device consists of two components are as: drug reservoir compartment and osmotically active compartment.
Incorporation of passage delaying food agents:
The food excipients like fatty acids, e.g. salts of myrestic acid change and modify the pattern of the stomach to a fed state, there by decreasing gastric emptying rate and permitting considerable prolongation of release. The delay in the gastric emptying after meals rich in fats is largely caused by saturated fatty acids with chain length of C10 to C14.
Ion exchange resin:
A coated ion exchange resin bead formulation has been shown to have gastric retentive properties, which was loaded with bicarbonates. Ion exchange resins are loaded with bicarbonate and a negatively charged drug is bound to the resin, resultant beads were then encapsulated in a semi-permeable membrane to overcome the rapid loss of carbon dioxide. Upon arrival in the acidic environment of the stomach and exchange of chloride and bicarbonate ions take place. As a result of this reaction carbon dioxide was released and trapped in a membrane thereby carrying beads towards the top of gastric content and producing a floating layer of resin beads in contrast the uncoated beads, which will sink quickly.
Design and fabrication of floating drug delivery system (FDDS):
(Jain N. K., 2008; Bandyopadhyay A.K., 2008)
Non - effervescent FDDS
Colloidal gel barrier system:
HBS of this type contains drug with gel forming or swellable cellulose type hydrocolloids, polysaccharides and matrix forming polymers. They help prolonging the GI residence time and maximize drug reaching its absorption site in the solution form ready for absorption. These systems incorporate high levels (20 to 75 % w/w) of one or more gel forming highly swellable cellulose type hydrocolloids e.g. hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodiumcarboxymethylcellulose polysaccharides and matrix forming polymers such as polycarbophil, polyacrylates and polystyrene incorporated either in tablets or capsules. When such a system comes in contact with the gastric fluid, the hydrochloride in the system hydrates and forms a colloidal gel barrier around its surface. The air trapped inside the swollen polymer maintains the density less than unity and confers buoyancy to these dosage forms. This gel barrier controls the rate of the fluid penetration into the device and consequent release of drug from it.
Figure 7: Colloidal gel barrier floating tablet
The HBS must comply with following three major criteria:
It must have sufficient structure to form cohesive gel barrier.
It must maintain specific density lower than that of gastric contents.
It should dissolve slowly to serve as reservoir for the delivery system.
A bilayer tablet can also be prepared to contain one immediate release and other sustained release layer. Immediate release layer delivers the initial dose whereas sustained release layer absorbs gastric fluid and forms a colloidal gel barrier on its surface. This results in system with bulk density lesser than that of gastric fluid and allows it to remain buoyant in the stomach for an extended period of time.
A multi-layer, sheath-like device buoyant in gastric juice showing sustained release characteristics has also been developed. The device consists of at least one dry self-supporting carrier film made up of water insoluble polymer matrix having a drug dispersed/dissolved therein, and a barrier film overlaying the carrier film. Both carrier and barrier films are sealed together along their periphery and in such a way as to entrap a plurality of small air pockets, which bring about the buoyancy to the laminated films.
Immediate Release Layer
Sustained release layer
Colloidal Gel Barrier
Sustained Release Layer
Figure 8: Bilayer intra-gastric floating tablet
Micro-porous compartment system:
This technology is comprised of encapsulation of a drug reservoir inside a micro-porous compartment with pores along its top and bottom surfaces. The peripheral walls of the drug reservoir compartment are completely sealed to prevent any direct contact of gastric mucosal surface with undissolved drug. In stomach, the floatation chamber containing entrapped air causes the delivery system to float over the gastric contents. Gastric fluid enters through the pores, dissolves the drug and carries the dissolved drug for continuous transport across the intestine for absorption.
Figure 9: Micro-porous intra-gastric FDDS
Multiple unit floating dosage forms have been developed from freeze-dried calcium alginate. Spherical beads of approximately 2.5 mm in diameter were prepared by dropping a sodium alginate solution into aqueous solution of calcium chloride, causing a precipitation of calcium alginate. These beads were then separated, snap frozen in liquid nitrogen and freeze-dried at 400C for 24 hours, leading to formation of porous system that maintained floating force for over 12 hours. They were compared with non-floating solid beads of same material. The latter gave a short residence time of 1 hour, while floating beads gave a prolonged residence time of more than 5.5 hours.
Floating systems comprising of calcium alginate core separated by an air compartment from a membrane of calcium alginate or a calcium alginate/polyvinyl alcohol (PVA) have also been developed. The porous structure generated by leaching of PVA (water soluble additive in coating composition) was found to increase membrane permeability and thus preventing the collapse of air compartment.
Hollow microspheres (micro-balloons) loaded with ibuprofen in their outer polymer shells were prepared by novel emulsion solvent diffusion method. The ethanol: dichloromethane solution of the drug and an enteric acrylic polymer were poured into an agitated aqueous solution of PVA that was thermally controlled at 40o C. The gas phase was generated in dispersed polymer droplet by evaporation of dichloromethane and formed an internal cavity in microsphere of polymer with drug. These micro-balloons floated continuously over surface of acidic solution media that contained surfactant, for greater than 12 hours in-vitro. The drug release was high in pH 7.2 than in pH 6.8.
Figure 10: Mechanism of micro-balloon formation by emulsion-solvent diffusion method
A drug delivery system can be made to float in the stomach by incorporating a floating chamber, which may be filled with vacuum, air or inert gas. The gas in floating chamber can be introduced either by volatilization of an organic solvent or by effervescent reaction between organic acids and bicarbonate salts.
Volatile liquid containing systems:
The GRT of a drug delivery system can be sustained by incorporating an inflatable chamber which contains a liquid e.g. ether or cyclo-pentane that gasifies at body temperature to cause the inflation of the chamber in the stomach. These devices are osmotically controlled floating systems containing a hollow deformable unit that can be converted from a collapsed to an expanded position and returned to collapsed position after an extended period. A deformable system consists of two chambers separated by an impermeable, pressure responsive, movable bladder. The first chamber contains the drug and the second chamber contains volatile liquid. The device inflates and the drug is continuously released from the reservoir into the gastric fluid. The device may also consist of bioerodible plug made up of PVA, polyethylene, etc. that gradually dissolves causing the inflatable chamber to release gas and collapse after a predetermined time to permit the spontaneous ejection of the inflatable system from the stomach.
Figure 11: Gastro inflatable drug delivery device
Intra-gastric, osmotically controlled drug delivery system consists of an osmotic pressure controlled drug delivery device and an inflatable floating support in bioerodible capsule. When the device reaches the stomach, bioerodible capsule quickly disintegrates to release the drug delivery system. The floating support is made up of a deformable hollow polymeric bag containing a liquid that gasifies at body temperature to inflate the bag. The osmotic pressure controlled part consists of two compartments, a drug reservoir compartment, and an osmotically active agent-containing compartment. The drug reservoir compartment is enclosed in a pressure responsive collapsible bag, which is impermeable to vapors and liquid, and has a drug delivery orifice. The osmotic compartment contains an osmotically active salt, and is enclosed within semi-permeable housing. In stomach, water is absorbed through the semi-permeable membrane into the osmotic compartment to dissolve the salt. An osmotic pressure thus created acts on collapsible bag and in turn forces the drug reservoir compartment to reduce its volume and release the drug solution through the delivery orifice. The floating support also contains a bioerodible plug that erodes after a predetermined time to deflate the support, which is then excreted from the stomach.
Figure 12: Intragastric osmotic controlled drug delivery system
Gas generating systems:
These buoyant delivery systems utilize effervescent reaction between carbonate/bicarbonate salts and citric/tartaric acid to liberate CO2 which gets entrapped in the jellified hydrochloride layer of the system, thus decreasing its specific gravity and making it float over chyme. Multiple unit type of floating pills that generate CO2 also has been developed. The system consists of sustained release pill as a seed, surrounded by double layer. The inner layer is an effervescent layer containing sodium bicarbonate and tartaric acid. The outer layer is swellable membrane layer. These kinds of systems float completely within 10 minutes and remain floating over an extended period of 6 to 24 hours.
Figure 13: Multiple unit oral floating dosage systems
Following figure shows mechanism of floating of effervescent drug delivery system:
Figure 14: Mechanism of effervescent drug delivery system
Recent advances in FDDS:
Floating multi-layer coated tablets:
Floating multi-layer coated tablets were designed based on gas formation. The system consists of a drugcontaining core tablet coated with a protective layer (hydroxypropyl methylcellulose), a gas forming layer (sodium bicarbonate) and a gas-entrapped membrane, respectively. The acrylic polymers (EudragitÂ® RL 30D, RS 30D, NE 30D) and ethylcellulose were suitable film for the system, and was chosen as a gas-entrapped membrane due to its high flexibility and high water permeability. The obtained tablets enabled to float due to the carbon-dioxide gas formation and the gas entrapment by polymeric membrane.
A gel-forming solution (e.g. sodium alginate solution containing carbonates or bicarbonates) swells and forms a viscous cohesive gel containing entrapped Carbon di-oxide bubbles on contact with gastric fluid. Formulations also typically contain antacids such as aluminium hydroxide or calcium carbonate to reduce gastric acidity. Because raft forming produce layer on the top of the gastric fluid, they are often used for gastroesophageal reflux treatment such as liquid gaviscon.
This system is based on a simple idea is that the dosage form contains a small internal magnet and a magnet placed on the abdomen over the position of stomach. The internal tablet guided by the oesophagus with an external magnet. These system seem to work, the external magnet must be positioned with a degree of precision that might compromise patient compliance.
Criteria for selection of drug candidate for GRDF: (Garg R., 2008)
Drugs required to exert local therapeutic action in the stomach e.g. Misoprostol, 5 to Flurouracil, antacids and anti-reflux preparations, anti-helicobacter pylori agents and certain enzymes.
Drugs exhibiting site-specific absorption in the stomach or upper part of the small intestine. e.g. Atenolol, Furosemide, Levodopa, p-Aminobenzoic acid, Piretanide, Salbutamol.
Drugs unstable in lower part of GI tract. e.g. Captopril.
Drugs insoluble in intestinal fluids (acid soluble basic drugs). e.g. Chlordiazepoxide, Chlorpheniramine, Cinnarizine, Dizapam, Diltiazem,
Metoprolol, Propranolol, Verapamil
Drugs with variable bioavailability. e.g. Sotalol hydrochloride and Levodopa.
Advantages of FDDS: (Jain N. K., 2008; Bandyopadhyay A.K., 2008)
It is advantageous for drugs absorbed through the stomach. for e.g. Riboflavin, ferrous salts, antacids.
It is not restricted to medicaments, which are absorbed from stomach, since it has been found that these are equally efficacious with medicaments which are absorbed from the intestine.
It is advantageous for drugs meant for local action in the stomach. for e.g. antacids, antiulcer drugs.
The dissolved drug gets available for absorption in the small intestine after emptying of the stomach contents. It is therefore expected that a drug will be fully absorbed from the floating dosage forms if it remains in the solution form even at the alkaline pH of the intestine.
It releases drug slowly and for prolonged period of time and hence reduces dosing frequency.
It reduces fluctuations in circulating blood level of drug as shown by the conventional dosage form.
It shows more uniform levels of drug in plasma.
As it prolongs drug release it helps to avoid night time dosing.
It reduces GIT irritation and other dose related side effects.
It increases patient compliance as the dosing frequency is reduced.
Disadvantages of FDDS: (Jain N. K., 2008)
The requirement of high levels of fluid in stomach for delivery system to float and work efficiently.
These systems require the presence of food to delay their gastric emptying time.
The drugs having solubility or stability problems in the highly acidic gastric environment or that are irritants to gastric mucosa are not good candidates for floating drug delivery system.
In case of bioadhesive system which form electrostatic and hydrogen bond with mucus, the acidic environment and mucus prevent bond formation at mucus polymer interface.
The dosage form designed to stay in stomach in the fasted state musts be capable of resisting the housekeeper waves of phase III of the MMC.
The drugs which are well absorbed along the entire GI tract and which undergoes significant first pass metabolism, may not be desirable candidates for FDDS, since slow gastric emptying lead to reduced systemic bioavailability.
Marketed preparations of FDDS: (Garg R., 2008)
Table 2: Marketed preparations of floating drug delivery systems
Levodopa & Benserazide
Alginic acid & bicarbonate