Overview on Trends in Development of Gastroretentive Drug Delivery System
Pavan Suradkar, Rakesh Mishra*, Tanaji Nandgude
Department of Pharmaceutics, Dr. D.Y. Patil Institute of Pharmaceutical Science & Research, Pimpri,
Pune -411018, Maharashtra, India.
*Corresponding Author E-mail: mishrarakesh287@gmail.com
ABSTRACT:
The present review on gastroretentive Drug Delivery Systems was aim with overview on various trends in development of gastroretentive approaches in the area of site-specific orally administered controlled release drug delivery. Gastroretentive dosage form can improve the delivery and performance of drug into the stomach because the drug remains in stomach for sufficient time of interval. The review summarized various physiological requirements and factors affecting gastric retention with merit and demerits of gastroretentive system. Various gastroretentive approaches designed and developed by researchers such as high density (sinking), floating system, bioadhesive, expandable, unfoldable, super porous hydrogel and magnetic systems were highlighted in the article.
KEYWORDS: Gastroretentive Drug Delivery System, Floating System, Effervescent System and Bioadhesive System.
INTRODUCTION:
Drug delivery system is become increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biological parameter pertinent to their performance. Controlled Drug Delivery system provide drug release at a predetermined, predictable and controlled rate to achieve high therapeutics efficacy with minimal toxicity. Oral formulation have place the various dosage form developed so far for human administration. In most of the cases, the conventional oral delivery system show limited bioavailability because of fast gastric emptying time among many other reason involved(1). However, the recent technological development has resulted too many novel pharmaceutical products, mainly novel controlled release drug delivery system to overcome this problem Gastro-Retentive drug delivery system (GRDDS). Drug delivery system, which can provide therapeutically effective plasma drug concentration for a longer period, thereby reducing the dosing frequency and minimizing fluctuation in plasma drug concentration at steady state by delivering the drug in a controlled and reproducible manner.
GRDDS has proved to be effective locally to treat gastric and duodenal ulcers, including esophagitis, by eradicating the deeply buried Helicobacter pylori from the submucosal tissue of the stomach(2). Gastroretentive Drug delivery system is an approach to prolonged the gastric residence time, thereby targeting site-specific drug release in upper Gastrointestinal tract (GIT) for local or systemic effects(3). Gastroretentive dosage forms can remain in the gastric region for long periods and hence significantly prolong the gastric retention time of drug. In addition, for local and sustained drug delivery to the stomach and proximal part of the small intestine, to treat certain conditions, prolonged gastric retention of the therapeutic moiety may offer numerous advantages including.
· Improved bioavailability
· Improved therapeutic efficacy
· Possible reduction of dose size
· Improves the drug solubility that is less soluble in high pH environment. E.g. weakly basic drugs like Domperidone, papaverine etc.
· Decrease drug wastage
· Also helps in achieving local delivery of drug to the stomach and proximal part of small intestine(4).
The strategies for delaying drug transit through the GIT are into following categories
1. Pharmacological approach
2. Physiological approach
3. Pharmaceutical approach(5)
The first two approaches are not used because of toxicity problems. The various pharmaceutical approaches are used for gastroretentive can be as follows.
1 Low density system/Floating system
2 High density system
3 Modified shape system
4 Mucoadhesive system
5 Expandable, unfoldable and swellable system
6 Magnetic systems.
Suitable Drug use for Gastro Retentive Drug Delivery System:
1) Drugs can be acting locally in the stomach misoprostol, 5-fluorouracil, antacids and antireflux preparations, anti-Helicobacter pylori agents, and certain enzymes.
2) Drugs that are primarily absorbed into the stomach.
3) Drugs that are less soluble at an alkaline pH (Drugs insoluble in intestinal fluids (acid soluble basic drugs)), chlordiazepoxide, chlorpheniramine, cinnarizine, diazepam, diltiazem, metoprolol, propranolol, quinidine, salbutamol, and verapamil.
4) Drugs are absorbed rapidly from GI tract.
5) Drugs that degrades in colon and unstable in lower part of GI tract eg. Captopril.
6) Drugs exhibiting site-specific absorption in the stomach or upper parts of the small intestine eg. Atenolol, furosemide, levodopa, p-aminobenzoic acid, piretanide, riboflavin-50-phosphate, salbutamol, sotalol, sulpiride, and thiamine.
7) Drugs with different bioavailability: sotalol hydrochloride and levodopa(6).
Advantages of GRDDS:
1. It is used for the treatment of peptic ulcer disease.
2. Commonly used for drugs with narrow absorption window in the small intestine.
3. Minimum dosing frequency.
4. Improved bioavailability of the drugs.
5. Used for drugs which are normally unstable in intestinal fluids.
6. Used to provide sustain the delivery of drug.
7. Used for maintaining maximum therapeutics drug concentration within the therapeutic window.
8. When there is a vigorous intestinal movement and a short transit time such as in certain type of diarrhoea, poor absorption is expected. Under such conditions it may be is advantageous to retain the drug in stomach to get a relatively better response.
9. There is not risk of dose dumping.
10. Avoid of gastric irritation, because of sustained release effect and uniform release of drug through the delivery system(7).
Fig.1. Drug absorption (a) Conventional dosage forms, (b) Gastroretentive drug delivery system.
Disadvantages of GRDDS:
1. Floating drug delivery system has limitation, that they require high level of fluids in stomach for floating and working more efficiently. So more water intake is needed with such dosage form.
2. These systems require sufficiently high levels of stomach fluids, for the system to float and to work efficiently.
3. It is not suitable for drugs with stability problem in stomach.
4. Drugs, which undergo extensive first pass metabolism, are not suitable candidates.
5. Drugs that are unstable in high acidic environment, very low solubility in acidic environment and causes irritation to gastric mucosa cannot be incorporated into GRDDS.
6. Floating drug delivery systems required high fluid level into the stomach to float and work effectively.
Anatomy and physiology of stomach:
Fig. 2 Diagram of human stomach
A) Anatomy:
The stomach is located below the diaphragm. There are various factors such as volume of food ingested; posture and skeletal build affect the extract position of stomach.
Anatomically stomach can be divided into four region are follows.
1. Fundus
2. Body
3. Antrum
4. Pylorus
1) Fundus and body:
The main function of fundus and body is storage for temporary period. The fundus adjust to the increase volume during eating by relaxing the fundal muscle fibers.The fundus exerts a steady pressure on the gastric content them toward the distal stomach. To pass through the pyloric valve into the small intestine (5).
2) Antrum:
Antrum is involved in mixing or grinding of food material. The particle should be in the range of 1-2 mm. The Antrum does this grinding.
3) Pylorus:
The pylorus it is the opening from the stomach into the duodenum. The main functions of the pylorus are to prevent the intestinal contents from entering to the stomach, when the small intestine contracts and to limit the passage of large food particles or undigested material into the intestine.
B) Stomach physiology:
Success for GRDDS relies on the understanding of stomach physiology and related gastric emptying process. When After a meal, the average volume of a stomach is about 1.5 to l, which varies from 250 to 500 ml during the inter-digestive phases. The part made up of fundus and the body acts as a reservoir of any undigested material while then antrum performs as the principal site for the mixing action, Being the lower part of the antrum works as a pump for gastric emptying by a propelling action. Pylorus acts to separate the stomach from the duodenum and plays a major role in gastric residence time of the ingested materials. However, the pattern of the gastric motility is different for the fasting and fed state. The gastric motility pattern is systematized in cycles of activity as well as quiescence. The duration of each cycle is 90120 min and it contains four phases, as mentioned in The motility pattern of the stomach is usually called migrating motor complex (MMC) (3).
C) pH:
pH of the stomach affects the performance of orally administered drug. The pH of stomach in fasted condition is about 1.5 to 2, and in fed condition, usually it is about 2 to 6. A large volume of water administered with an oral dosage forms changes the pH of the stomach to the pH of water initially. This changes occur due to stomach does not have sufficient time to produce as much quantity of acid before emptying of liquid from the stomach. Therefore, it doesn't improve dissolution of basic drugs. In this condition basic drugs will have a better chance to dissolve in fed condition rather than in a fed condition (8).
D) Gastric motility:
There are three layer of stomach, which produces the coordinated movement of the gastric content such as, outer longitudinal muscle layer, inner circular muscle layer, and an oblique layer. The motility pattern of the stomach at the time of administration of dosages from is different in digestive or fasted and interdigestive or fed conditions.
There are four phases of stomach movement in the fasted state.
It is divided into four phase.
1) Basal phase
2) Prebrust phase
3) Brust phase
4) Short transitional phase
In phase one (basal phase):
There is no contraction or secretion. It last upto 40 to 60 min.
In phase two (prebrust phase):
There are irregular contraction and bile secretion. During this phase, pressure rises to 5 to 40 mm of Hg during contraction. It is last up to 20 to 40 min.
In phase, three (burst phase):
Mucus discharge take place. In this phase, the frequency and amplitude of contraction is at the peak. Although this is very short phase, last up to 4 to 6 min. During this phase, the baseline pressure increases substantially.
The fourth phase:
It is a short transitional period, which is last up to 0 to 5 min. and originated between phases 3 and 1.
This phases activity moves along with the oesophagus, stomach, antrum, duodenum, jejunum, ileum, and caecum. Almost it takes about 2 hour for this phase to move through stomach to ileocecal junction. This phase acts as a cleaning phase, and also known as housekeeper wave.
Fig. 3 Diagram of Four phase of migrating motor complex (MMC).
Table 1 Transit time in each segment of the gastrointestinal tract
|
Segment |
Liquid |
Solid |
|
Stomach |
10-30 min |
1-3 hours |
|
Duodenum |
≤60 sec |
≤60 sec |
|
Jejunum and ileum |
3 hours ± 1.5 hours |
4 hours ± 1.5 hours |
|
Colon |
-------- |
20 50 hours |
Factors affecting gastric retention:
1) Density:
Density of the dosage form should be less than 1, the gastric contents (1.004gm/ml). It should be in the range of 1g/cm3 to 2.5g/cm3.
2) Size:
Dosage form unit with a diameter of more than 7.5 mm are reported to have an increased GRT competed to with those with a diameter of 9.9 mm.
3) Shape:
The dosage form with a shape tetrahedron and spherical shape devices with a flexural modulus of 48 and 22.5 kilo pounds per square inch (KSI) are reported to have better Gastric retention time 90 to 100% retention at 24 hours compared with other shapes(9).
4) Fed or Unfed State:
Under fasting conditions, the GIT motility is characterized by periods of strong motor activity or the migrating myoelectric complexes (MMC) that occurs every 1.5 to 2 hours. The Migrating motor complex sweeps undigested material from the stomach and if the timing of administration of the formulation coincides with that of the MMC the Gastro retentive time can be expected to be very short. When in the fed state MMC is delayed and GRT is considerably longer.
5) Single or multiple unit formulation:
Multiple or single unit formulations have a better predictable release profile and insignificant impairing effect of performance due to failure of units to allow co-administration of units with different release profiles of the containing incompatible substances and allow a larger margin of safety against an dosage form and failure compared with single unit dosage forms.
6) Nature of the meal:
Feeding of indigestible polymers of fatty acid salts can change the motility pattern of the stomach to a fed state and decreasing the gastric emptying rate and prolong the drug release.
7) Caloric Content:
Gastro retentive tract can be increased caloric between 4 to 10 hours with a meal that is high in proteins and fats.
8) Frequency of feed:
The Gastro Retentive Tract can increase by over 400 min, when successive meals are given compared with a single meal due to the low frequency of Migrating motor complex.
9) Gender:
Generally, females have slower gastric emptying rates than males, Stress increases of the gastric emptying rates then depression slows it down.
10) Age:
Eged people especially those over 70 years have a significantly longer release for GRT.
11) Posture:
GRT can vary between supine and upright ambulatory states of the patients.
12) Diseased state of the individual:
Biological factors also affect the gastric retention e.g. Crohns disease, gastrointestinal diseases and diabetes.
13) Concomitant drug administration:
Anti-cholinergics like atropine and propentheline opiates like codeine and prokinetic agents like metoclopramide and cisapride.
14) Other factors:
Diseased states of the individual (chronic disease, diabetes etc.) Body mass index Physical activity Molecular weight and lipophilicity of the drug depending on its ionization state.
Approaches through which gastric retention are possible: e
Various approaches have a similar to increase the retention of an oral dosage form in the stomach, for example, bioadhesive approach in which the adhesive capacity of some polymer with glycoprotein is closely applied to the epithelial surface of stomach, and other approaches include high density and low density approach are done.
1) High density approach:
For preparing this type of formulations the density of the pellets should be higher weight than the stomach fluid. It would be at least 1.50 g/ml. In this type, the drug can be coated or mixed with heavy, nontoxic materials such as barium sulphate, titanium dioxide, etc.
2)Floating or Low density approach:
Floating systems come under low density approach of GRT, In this approach the density of pellets should be less than 1 g/ml, it should be float to the pellets and tablet in the gastric fluid then release the drug slowly for a prolonger period of time(10).Then This type is also called as Hydrodynamically Balanced System or (HBS).
Fig. 4: Diagram of Gastro retentive drug delivery system (low density and high density systems).
Table 2 Comparison of High density and Low-density system.
|
Sr. no |
High density system |
Low density Floating system |
|
1 |
Density of pellets or tablets greter than density of stomach fluid. |
Density of pellets or tablet should less than 1g/ml. |
|
2 |
Drugs are coated or mixed with heavy nontoxic materials. e.g. barium sulphate, titanium dioxide etc. |
Low bulk density systems are designed into such a manner for that it floats in gastric fluid and release the drug slowly for a prolonged Period. |
|
3 |
Density of pellet / tablet should be at least 150 g/ml |
Low bulk density systems, designed in Such a manner that it floats in gastric fluid and release the drug slowly for a longer period. |
|
4 |
High density systems |
Also called Hydrodynamic balanced System. |
Classification of floating system:
· Effervescent system
· Non effervescent systems
Effervescent systems:
Effervescent floating drug delivery systems generate gas (CO2), thus reduce the density of the system, and remain buoyant in the stomach for a prolonged period and release the drug slowly at a desired rate. The main ingredients of effervescent system include swellable polymers like chitosan, methylcellulose and effervescent compounds such as citric acid, sodium bicarbonate, citric acid and tartaric acid. Gas-forming agents were also incorporated so as soon as the gas formed, the density of the system was reduced and thus, the system tended to float in the gastric environment. Prepared the effervescent floating tablet of famotidine. They found that the addition of gel forming polymer methocel (K100 and K15M) and gas-generating agent sodium bicarbonate along with citric acid was essential to achieve in vitro buoyancy.
Following are the types of gas generating GRDDS.
a. Conventional matrix tablets
b. Layered matrix tablets
c. Core coated matrix tablets.
Non - effervescent system:
Non-effervescent floating drugs delivery systems are normally formulated by from gel forming or highly soluble cellulose type hydrocolloid, polysaccharides.
Commonly used recipients in non-effervescent GRDDS are
1. Hydroxypropyl methylcellulose (HPMC)
2. Polyacrylate
3. Polyvinyl acetate
4. Carbopol
5. Agar
6. Sodium alginate
7. Calcium chloride
8. Polyethylene oxide
9. Polycarbonate
This system can be further divided into the sub type.
Hydrodynamically balance system:
Sheth and Tossounian first formulated these hydrodynamically balanced systems. These systems contains drug with gel-forming hydrocolloids meant to remain buoyant in the stomach for prolonged period of time. These are single-unit dosage form, mainly contain one or more gel-forming hydrophilic polymers (9).
Commonly used excipients to develop these system are as follows.
1. Hydroxypropyl methylcellulose (HPMC)
2. Hydroxethyl cellulose (HEC)
3. Hydroxypropyl cellulose (HPC)
4. Sodium carboxymethyl cellulose (NaCMC)
5. Polycarbophil
6. Polyacrylate
7. Polystyrene
8. Agar
9. Carrageenan
10. Alginic acid.
Microballoons/ Hollow microsphere:
Microballoons / hollow microspheres loaded with drugs in their other polymer shelf was formulated by simple solvent evaporation or solvent diffusion / evaporation methods. to prolong the gastric retention time (GRT) of the dosage form. Commonly used polymers to develop these systems are polycarbonate, cellulose acetate, calcium alginate, Eudragit S, agar and low methoxylated pectin etc. Buoyancy and drug release from dosage form are dependent on quantity of polymers, the plasticizer polymer ratio and the solvent used for formulation. The microballoons floated continuously over the surface of an acidic dissolution media containing surfactant for >12hours. At present hollow microspheres are considered to be one of the most promising buoyant systems because they combine the advantages of multiple-unit system and good floating.
Alginate beads:
Talukdar and Fassihi recently developed a multiple-unit floating system based on cross-linked beads. They were made by using Ca2+ and low methoxylated pectin (anionic polysaccharide) or Ca2+ low methoxylated pectin and sodium alginate. In this approach, generally sodium alginate solution is dropped into aqueous solution of calcium chloride and causes the precipitation of calcium alginate. These beads are then separated and dried by air convection and freeze drying, leading to the formulation of a porous system, which can maintain a floating force for over 12 hrs. These beads improve gastric etention time (GRT) more than 5.5 hrs. Microporous compartment system: This approach is based on the principle of the encapsulation of a drug reservoir inside a microporous compartment with pores along its top and bottom walls. The peripheral walls of the device were completely sealed to present any direct contact of the gastric surface with the undissolved drug. In the stomach the floatation chamber containing entrapped air causes the delivery system to float in the gastric fluid. Gastric fluid enters through the aperture, dissolves the drug and causes the dissolved drug for continuous transport across the intestine for drug absorption.
Bioadhesive systems:
Bioadhesive systems are those systems, which bind to the gastric epithelial cell surface, which serve as a potential means of extending the gastric retention of drug delivery system in the stomach by increasing the intimacy and duration of contact of drug with the biological membrane. These systems permit a given drug delivery system to be incorporated with a bioadhesive agent. A bioadhesive substance is a natural or synthetic polymer that enables a device to adhere to the stomach and capable of producing an interaction based on hydration mediated, receptor mediated or bonding mediated adhesion with the biological membrane of the gastrointestinal mucosa. Some promising excipients that have been used are carbopol, chitosan, polycarbophil, lectins etc.(11)
Swelling systems:
These are the dosage forms, which after swallowing, swell to an extent that prevents their exit from the pylorus. As a result, the dosage form retains in the stomach for a longer period of time. These systems may be named as plug type systems. Sustained and controlled drug release may be achieved by selection of polymer of proper molecular weight and swelling of the polymer retards the drug release. On coming in contact with gastric fluid, the polymer imbibes water and swells. The extensive swelling of these polymers is due to the presence of physical/chemical cross-links in the hydrophilic polymer network. These cross-links prevent the dissolution of the polymer and hence maintain the physical integrity of the dosage form.
Expandable systems:
A dosage form in the stomach will withstand gastric transit if it is bigger than the pyloric sphincter. Thus, three configurations are required: a small configuration for oral intake, an expanded gastroretentive form and a final small form enabling evacuation following drug release(12). Thus, gastroretentivity is improved by the combination of substantial dimension with high rigidity of dosage form to withstand peristalsis and mechanical contractility of the stomach. Unfoldable and swellable systems have been investigated and recently tried to develop an effective gastroretentive drug delivery(10, 13-18).
Superporous hydrogels:
Super porous hydrogel are swellable systems that differ sufficiently from the conventional types. Absorption of water by conventional hydrogel is a very slow process and several hours may be needed to reach an equilibrium state during which premature evacuation of the dosage form may occur. Superporous hydrogels have an average pore size >100 μm which swell to an equilibrium size within a minute, due to rapid uptake of water by capillary wetting through numerous interconnected open pores. Moreover, they swell to a large size (swelling ratio 100 or more) and are intended to have sufficient mechanical strength to withstand pressure by gastric contraction. This is achieved by co-formulation of a hydrophilic particulate material, Ac-Di-Sol (croscarmellose sodium).
Magnetic systems:
This system is based on a simple idea that the dosage form contains a small internal magnet, and a magnet placed on the abdomen over the position of the stomach. Using an extracorporeal magnet, gastric residence time of the dosage form can be enhanced for a prolonged period of time.
Ion exchange resin system:
Ion exchange resin system is a system, which is formulated to have gastroretentive properties. Ion exchange resin beads are loaded with bicarbonate and a negatively charged drug is bound to the resin. The resultant beads were then encapsulated in a semipermeable membrane to overcome the rapid loss of carbon dioxide. Upon arrival in the acidic environment of the stomach, an exchange of chloride and bicarbonate ions takes place. Because of this reaction, carbon dioxide was released and trapped in the membrane thereby carrying beads towards the top of gastric content and producing a floating layer of resin beads in contrast to the uncoated beads, which will sink quickly. Various merits and demerits of different approaches of the GRDDS are summarized in table 3.
Raft forming system:
Various attempts have been made to retain the dosage form in the stomach as a way of increasing the retention time. Among the various attempts, the raft forming system is an advanced revolution in oral controlled drug delivery. Raft forming systems have received much attention for the delivery of the drug for gastrointestinal infections and disorders(19-23).
Table 3 Merits and demerits of different approaches of the gastroretentive drug delivery system.
|
Approaches |
Detail |
Merits |
Demerits |
|
High density system |
Sinking systems that retained at the bottom of the stomach. In this system density of pellets/tablets > density of stomach fluid. |
These systems with a density of about 3 g/cm3 retained in the antrum part of the stomach and are capable of withstanding its peristaltic movements and allow the release of drug for a prolonged period of time. |
Technically difficult to manufacture such formulations with high amount of drug (>50%). Technically also difficult to achieve a density of about 2.8 g/cm3. Effectiveness of this system in human beings was not observed and thus such system has not been marketed. Retention of high density systems in the antrum part under the migrating waves of the stomach is questionable. |
|
Low density system |
System causes buoyancy in gastric fluid. In this system density of pellets/tablets density of stomach fluid. |
Improves better patient compliance. No risk of dose dumping. Enhance the bioavailability of a drug. Reduce the frequency of dosing. This system floats on gastric fluid and causes release of the drug slowly for a longer period of time. The HBS are advantageous for drugs that are absorbed through the stomach e.g.ferrous salts and for drugs meant for local action in the stomach and treatment of peptic ulcer disease e.g. antacids. |
Single unit low density system is associated with problems such as sticking together or being obstructed in the gastrointestinal tract, which may have a potential danger of producing irritation. Single unit low density system is unreliable and non-reproducible in prolonging gastric residence time in the stomach when administered orally. One drawback of hydrodynamic ally balanced systems is that this system, being a matrix formulation, consists of a blend of drug and low-density polymers. The release kinetics of the drug cannot be changed without changing the floating properties of the dosage form and vice versa. |
|
Swelling system |
These are the dosage forms, which after swallowing, swell to an extent that prevents their exit from the pylorus. As a result, the dosage form is retained in the stomach for a longer period of time. |
Improves better patient compliance. No risk of dose dumping. Enhance the bioavailability of the drug. Reduce the frequency of dosing. Allow the release of drug for a prolonged period of time. |
Swelling of the dosage form causes floating of the dosage form and thus the system requires high fluid level in the stomach for the floating of the dosage form and to work effectively. The floating systems in patients with achlorhydria can be questionable in case of swellable systems, faster swelling properties are required and complete swelling of the system should be achieved well before the gastric emptying time. Bioadhesive system These systems are used to localize a delivery device within the lumen and cavity of the body to increase the drug absorption process in a site-specific manner. Improves patient compliance. No risk of dose dumping. Enhance the bioavailability of the drug. Reduce the frequency of dosing. Bioadhesion is difficult to maintain due to rapid turnover of mucin in GIT. |
|
Bioadhesive system |
These systems are used to localize a delivery device within the lumen and cavity of the body to increase the drug absorption process in a site-specific manner. |
Improves patient compliance. No risk of dose dumping. Enhance the bioavailability of the drug. Reduce the frequency of dosing. |
Bioadhesion is difficult to maintain due to rapid turnover of mucin in GIT. |
|
Expandable system |
Use of size-increasing concept for gastroretention. This system is capable of increasing in size relative to the initial dimensions. |
Dosage form is small enough to be swallowed, and thus not cause gastric obstruction either singly or by accumulation. Increase in size prevents the system from passing via the pylorus and provides for its prolonged stay in the stomach. |
Time consuming. Difficulty in formulation. Not most widely used. |
|
Magnetic system |
Dosage forms contain a small internal magnet and a magnetis placed in the abdomen over the position of the stomach that retains the dosage form in the gastric region. |
Magnetic system serves as a potential means of extending the gastric retention of the drug in the stomach by increasing duration of contact of system in the gastric region. |
Despite numerous reports about successful tests, the real applicability of such systems is doubtful because the desired results can be achieved only if the external magnet is to be positioned with high degree of precision. The external magnet must be positioned with a degree of precision that might compromise patient compliance. Not better patient compliance. Not most widely used. |
|
Ion-exchange resin System |
Coated ion exchange resin beads are loaded with bicarbonate and a negatively charged drug is bound to the resin. The resultant beads were then encapsulated in a semi-permeable membrane to overcome the rapid |
This system floats on the gastric fluid due to exchange of chloride and bicarbonate ions which further causes release of carbon dioxide. Thus the drug was released slowly for a longer period of time. |
Not most widely used. Time consuming. Very expensive to formulate this system. |
The raft forming system is one of the approaches, which involve the formulation of effervescent floating liquid with in situ gelling properties, which has been assessed for sustaining drug delivery and targeting. Moreover, the gels formed in situ remained intact for more than 48 h to facilitate sustained release of drugs. The mechanism of the raft forming system involves the formation of continuous layer called a raft. The system involves the formation of a viscous cohesive gel in contact with gastric fluids, wherein each portion of the liquid swells forming a continuous layer called a raft. The layer of the gel floats on the gastric fluid because it has bulk density less than the gastric fluid, as low density is created by the formation of CO2(2). So the system remains buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. The gel formed from in situ gelling, being lighter than gastric fluid, floats over the stomach contents or adheres to the gastric mucosa due to the presence of a bioadhesive nature of the polymer and prevents the reflux of gastric content into the esophagus by acting as a barrier between the stomach and the esophagus(24-26). Thus it produces retention of dosage form and increases gastric residence time resulting in prolonged drug delivery in gastrointestinal tract. When the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. After release of the drug, the residual system is emptied from the stomach. This results in an increased gastro retention time and a better control of the fluctuations in plasma drug concentration(27,28).
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Received on 09.04.2019 Modified on 18.05.2019
Accepted on 20.06.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(11):5633-5640.
DOI: 10.5958/0974-360X.2019.00975.2