FLOATING DRUG DELIVERY SYSTEM AS AN APPROACH TO INCREASE THE GASTRIC RETENTION OF DRUGS
School of Pharmaceutical Sciences, Shoolini University
Solan, H.P. India
The gastro retentive drug delivery system is a novel approach for the drugs having narrow absorption window in the gastrointestinal tract and has poor absorption. Gastro retentive drug delivery system mainly prolongs the gastric emptying time, thereby targeting site-specific drug release. Several techniques such as floating drug delivery system, low density system, raft system, mucoadhesive system, high density system, super porous hydro gel and magnetic system, have been employed. The physiological problems like short gastric residence time and unpredictable gastric emptying time were overcome with the use of floating dosage forms which provide opportunity for both local and systemic effect. Floating drug delivery system enable prolonged and continuous input of the drug to the upper part of the gastro retentional tract and improve the bioavailability of medication that is characterized by a narrow absorption window. The present review addresses briefly about the floating drug delivery system.
Reference Id: PHARMATUTOR-ART-1287
Floating drug delivery systems are retained in the stomach and are useful for drugs that are poorly soluble or unstable in intestinal fluid. Oral administration is the most convenient and preferred means of any drug delivery to the systemic circulation. The reason that the oral route achieved such popularity may be in part attributes to its ease of administration . Oral sustained drug delivery system is complicated by limited gastric residence time (GRTs). Fast GI transit prevents complete drug release in the absorption zone and reduce the efficacy of the administered dose since the majority of drugs are absorbed in stomach or the upper part of small intestine. To overcome these limitations, various approaches have been proposed to increase gastric residence of drug delivery system in the upper part of the gastrointestinal tract includes floating drug dosage system (FDDS), swelling or expanding system and other delayed gastric emptying devices. Among these systems, FDDS have been most commonly used.
Floating drug delivery system
Floating drug delivery system have a bulk density less than that of gastric fluids and so remain buoyant in the stomach without affecting the gastric emptying rate for a prolong period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. After release of drug, the residual system is emptied from the stomach. This result in an increased GRT and a better control of fluctuation in plasma drug concentration. However, beside a minimal gastric content needed to allow the proper achievement of the buoyancy retention principle, a minimal level of floating force (F) is also required to keep the dosage form reliably buoyant on the surface of meal. To measure the floating force equivalent to F (as a function of time) that is required to maintain the submerged object. The object floats better if RW is on the higher positive side. This apparatus helps in optimizing FDDS with respect to stability and durability of floating forces produced in order to prevent the drawbacks of unforeseeable intragastric buoyancy capability variation.
RW or F = F (buoyancy) – F (gravity)
= (Df – Ds ) gV
Where RW = total vertical force, Df = fluid density, Ds = object density, V = volume and g = acceleration due to gravity.
Classification of floating drug delivery system
Based on the mechanism of buoyancy FDDS can be classified into
A. Single unit floating dosage system
a) Effervescent system (gas-generating system)
b) Non-effervescent system
B. Multiple unit floating dosage system
a) Non-effervescent system
b) Effervescent system (gas-generating system)
c) Hollow microsphere
C. Raft forming system
A.Single unit floating dosage system
a) Effervescent system (gas-generating system)
These buoyant system utilized matrices prepared with swellable polymer like HPMC, polysaccharide like chitosan, effervescent component like sodium bicarbonate, citric acid and tartaric acid or chamber containing a liquid that gasifies at body temperature. The optimal stoichiometric ratio of citric acid and sodium bicarbonate, for gas generation is reported to be 0.76:1. The common approach for preparing these systems involves resin beads loaded with bicarbonate and coated with ethyl cellulose. The coating, which is insoluble but permeable, allows permeation of water. Thus, carbon dioxide is released, causing the beads to float in the stomach.
Excipients used most commonly in these systems include HPMC, polyacrylate polymer, polyvinyl acetate, carbopole, agar, sodium alginate, calcium chloride, polyethylene oxide and polycarbonates.
Ozdemir et al prepared floating bilayer tablets with controlled release for furosemide. The low solubility of drug could be enhanced by using the kneading method, preparing a solid dispersion with β-cyclodextrin mixed in a 1:1 ratio. One layer contained the polymer HPMC 4000, HPMC 100, and CMC (for the control of drug delivery) and the drug. The second layer contained the effervescent mixture of sodium bicarbonate and citric acid. Radiographic studies on 6 healthy males volunteers showed that floating tablets were retained in stomach for 6 hours and further blood analysis studies showed that bioavailability of these tablets was 1.8 times that of the conventional tablets was decreased and prolonged in the case of floating dosage forms.
Penners et al prepared an expandable tablet containing mixture of polyvinyl lactams and polyacrylates that swell rapidly in an aqueous environment and thus stays in stomach over an extended period of time. In addition to this, gas forming agents were also incorporated so as soon as the gas formed, the density of system was reduced and thus the system tended to float on the gastric environment.
Talwar et al prepared a once-daily formulation for oral administration of ciprofloxacin. The formulation was composed of 69.9% ciprofloxacin base, 0.34% sodium alginate, 1.03% xanthum gum, 13.7% sodium bicarbonates, and 12.1% cross-linked poly vinyl pyrrolidine. The cross linked PVP initially and the gel forming polymer later formed a hydrated gel matrix that entrapped the gas, causing the tablet to float and be retained in the stomach. The hydrated gel matrix created a diffusion path for the drugs, resulting in sustained release of the drug.
b) Non-effervescent system
This type of system, after swallowing, swells unrestrained via imbibitions of gastric fluid to an extend that prevent their exit from the stomach.
Shah S.H. et al system may be referred to as the ‘plug-type systems’ since they have a tendency to remain lodged near the pyloric sphincter. One of the formulation method of such dosage forms involves the mixing of drug with a gel, which swells in contact with gastric fluid after oral administration and maintains a relative integrity of shape and a bulk density of less than one within gelatinous barrier. The air trapped by the swollen polymer confers buoyancy to these dosage forms. Examples of this type of FDDS include colloidal gel barrier, micro porous compartment system, alginate beads, and hollow microsphere. Another type is a fluid-filled chamber which include incorporation of a gas filled floatation chamber into a micro porous component that houses a drug reservoir. Aperture or openings are present along the top and bottom walls through which the gastrointestinal tract fluid enter to dissolve the drug. The other two walls in contact with the fluid are sealed so that the undissolved drug remains therein. The fluid present could be air, under partial vacuum or any other suitable gas, liquid, or solid having an appropriate specific gravity and an inert behavior. The device is of swallowable size, remains afloat within the stomach for prolonged time, and after the complete release the shell disintegrates, passes off to the intestine, and is eliminated.
Gas filled floatation chamber
A newer self-correcting floatable asymmetric configuration drug delivery system has a 3-layer matrix to control the drug release. This 3-layer principle has been improved by development of an asymmetric configuration drug delivery system in order to modulate the release extend and achieve zero-order release kinetics by initially maintaining a constant area at the diffusing front with subsequent dissolution/erosion towards the completion of the release process. The system was designed in such a manner that it floated to prolong gastric residence time in vivo, resulting in longer total residence time within the gastrointestinal tract environment with maximum absorptive capacity and consequently greater bioavailability. This particular characteristic would be applicable to drugs that have pH dependent solubility, a narrow window of absorption, and are absorbed by active transport from either proximal or distal portion of the small intestine.
Yang et al developed a swellable asymmetric triple layer tablet with floating ability to prolong the gastric residence time of triple drug regimen (tetracycline, metronidazole, and clarithromycin) in Helicobacter pylori-associated peptic ulcer using HPMC and poly (ethylene oxide) (PEO) as the rate-controlling polymeric membrane excipients. Tetracycline and metronidazole were incorporated into the core layer of the triple layer matrix for controlled delivery, while bismuth salt was included in one of the outer layer for instant release. The floatation was accomplished by incorporating a gas-generating layer consisting of sodium bicarbonates and calcium carbonate with swellable chamber. Over 6 to 8 hours of sustained delivery of tetracycline and metronidazole was achieved with this dosage form which was still floating.
Streubel et al prepared single-unit floating tablets based on polypropylene foam system and matrix foaming polymer. Highly porous foam powder in matrix tablets provided density much lower than the density of released medium. It was concluded that varying the ratio of matrix-foaming polymer and the foam powder could alter the drug release pattern effectively.
Wu et al prepared floating sustained release tablets of nimodipine by using HPMC and PEG 6000. Prior to formulation of floating tablets, nimodipine was incorporated into poloxamer-188 solid dispersion after which it was directly compressed into floating tablets. It was observed that by increasing the HPMC and decreasing the PEG 6000 content a decline in in-vitro release of nimodipine was observed.
Nur and Zhang et al prepared floating tablet of captopril using HPMC (4000 and 15000 cps) and carbopol 934P. It was concluded that the buoyancy of tablet is governed by both the swelling of hydrocolloid particle on the tablet surface when it contacts the gastric fluid and the presence of internal voids in the centre of tablet (porosity). A prolonged release from these floating tablets was observed as compared with the conventional tablets and a 24-hours controlled release from the dosage foam of captopril was achieved. Single-unit formulations are associated with problems such as sticking together or being obstructed in the gastrointestinal tract, which may have a potential danger of producing irritation. The main drawback of such system is “all or none” phenomenon. In such cases there is danger of passing of the dosage forms to intestinal part. To overcome this difficulty multiple unit dosage forms are designed.
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