Gastro Retentive Drug Delivery Systems-a Novel Approaches of Controlled Drug Delivery Systems
Debjit Bhowmik*, Rishab Bhanot, Darsh Gautam, Parshuram Rai, K. P. Sampath Kumar
Himachal Institute of Pharmaceutical Education and Research, Nadaun, Hamirpur, H. P.
Department of Pharmacy, Coimbatore government medical college, Coimbatore
*Corresponding Author E-mail: debjit_cr@yahoo.com
Abstract:
Gastro-retentive drug delivery technology is designed to retain a drug in the upper gastrointestinal tract for a prolonged period of time to allow efficient absorption. This is important because almost 40% of all new drugs have poor bioavailability from the lower gastrointestinal tract. Gastric retention will provide advantages such as the delivery of drugs with narrow absorption windows in the small intestinal region. Also, longer residence time in the stomach could be advantageous for local action in the upper part of the small intestine, for example treatment of peptic ulcer disease. Furthermore, improved bioavailability is expected for drugs that are absorbed readily upon release in the GI tract. These drugs can be delivered ideally by slow release from the stomach. The application of our unique gastro-retentive technology include: Use with drugs targeting absorption in the upper segment of the small intestine, Use with drugs targeting absorption in just the stomach, Suitable for high drug loads, Use with a range of drugs, including poorly soluble molecules.
KEY WORDS: Gastro-retentive drug delivery, Controlled drug delivery system, Gastric retention.
INTRODUCTION:
Oral drug delivery is the most widely utilized route of administration among all the routes that have been explored for systemic delivery of drugs via pharmaceutical products of different dosage form. Oral route is considered most natural, uncomplicated, convenient and safe due to its ease of administration, patient acceptance, and cost-effective manufacturing process1. All the pharmaceutical products formulated for systemic delivery via the oral route of administration, irrespective of the mode of delivery (immediate, sustained or controlled release) and the design of dosage form (solid dispersion or liquid), must be developed within the intrinsic characteristics of GI physiology. Therefore the scientific framework required for the successful development of oral drug delivery systems consists of basic understanding of Physicochemical, pharmacokinetic and Pharmacodynamic characteristics of the drug. The anatomic and physiologic characteristics of the gastrointestinal tract. Physicochemical characteristics and the drug delivery mode of the dosage form to be designed. Conventional oral controlled dosage forms suffer from mainly two adversities2. The short gastric retention time (GRT) and unpredictable gastric emptying time (GET). A relatively brief GI transit time of most drug products impedes the formulation of single daily dosage forms. Altering the gastric emptying can overwhelm these problems. Therefore it is desirable, to formulate a controlled release dosage form that gives an extended GI residence time. One of the most feasible approaches for achieving a prolonged and predictable drug delivery profiles in gastrointestinal tract is to control the gastric residence time (GRT) using gastro retentive dosage forms (GRDFs) that offer a new and better option for drug therapy3. Dosage forms that can be retained in stomach are called gastro retentive drug delivery systems (GRDDS). GRDDS can improve the controlled delivery of drugs that have an absorption window by continuously releasing the drug for a prolonged period of time before it reaches its absorption site thus ensuring its optimal bioavailability. During the last decade many studies have been performed concerning the sustained release dosage form of drugs, which have aimed at the prolongation of gastric emptying time (GET) The GET has been reported to be from 2 to 6 hours in humans in the fed state. Accordingly orally, sufficient bio availability and prolongation of the effective plasma level occasionally cannot be obtained. Controlled release drug delivery systems that can be retained in stomach for a long time are important for drug that are degraded in intestine or for drugs like antacids or certain enzymes that should act locally in the stomach. If the drugs are poorly soluble in intestine due to alkaline pH, gastric retention may increase solubility before they are emptied, resulting in improved gastrointestinal absorption of drugs with narrow absorption window as well as for controlling release of drugs having site-specific absorption limitation4.
GASTRORETENTIVE DOSAGE FORM (GRDF):
Dosage forms that can be retained in stomach are called gastro retentive drug delivery systems (GRDDS). GRDDS can improve the controlled delivery of drugs that have an absorption window by continuously releasing the drug for a prolonged period of time before it reaches its absorption site thus ensuring its optimal bioavailability.
The stomach is situated in the left upper part of the abdominal cavity immediately under the diaphragm. Its size varies according to the amount of distension, up to 1500 ml following a meal; after food has emptied, a collapsed state is obtained with resting volume of 25-50 ml. The stomach is anatomically divided into 3 parts, fundus, body and antrum (or pylorus). The proximal stomach, made up of fundus and body regions serves as a reservoir for ingested materials while the distal region (antrum) is the major site of mixing motions, acting as a pump to accomplish gastric emptying.
The process of gastric emptying occurs both during fasting and fed states, however the pattern of motility differs markedly in the two states. Two distinct patterns of gastrointestinal motility and secretion exist corresponding to the fasted and fed states. As a result the bioavailability of orally administered drugs will vary depending on the state of feeding. In the fasted state, it is characterized by an interdigestive series of electrical event and cycle, both through the stomach and small intestine every 2-3 hrs. This activity is called the interdigestive myoelectric cycle or Migrating motor complex (MMC) is often divided into four consecutive phases: basal (Phase I) pre burst (Phase II), burst (Phase III), and Phase IV intervals.
PHASE I the quiescent period, lasts from 30 to 60 mins and is characterized by a lack of secretary, electrical and contractile activity. PHASE II, exhibits intermittent activity for 20-40 min, during which the contractile motions increase in frequency and size. Bile enters the duodenum during this phase, whereas gastric mucus discharge occurs during the latter part of phase II and throughout phase III. PHASE III is a short period of intense large regular contractions, termed “housekeeper waves” that sweep off undigested food and last 10-20 min. PHASE IV is the transition period of 0-5 mins between Phase III and I.
The motor activity in the fed state is induced 5-10 mins after ingestion of a meal and persists as long as food remains in the stomach. The larger the amount of food ingested, the longer the period of fed activity, with usual time spans of 2-6 h, and more typically, 3-4 h, with phasic contractions similar to Phase II of MMC .
When CRDDS are administered in the fasted state, the MMC may be in any of its phases, which can significantly influence the total gastric residence time (GRT) and transit time in gastrointestinal tract.
This assumes even more significance for drugs that have an absorption window because it will affect the amount of time the dosage form spends in the region preceding and around the window. The less time spent in that region, the lower the degree of absorption. On the other hand, in the fed stomach the gastric retention time (GRT) of non disintegrating dosage forms depends mostly on their size and composition and caloric value of food.
From the discussion of the physiological factors in stomach, to achieve gastro retention, the dosage form must satisfy some requirements. One of the key issues is that the dosage form must be able to withstand the forces caused by peristaltic waves in the stomach and constant grinding and churning mechanisms. It must resist premature gastric emptying and once the purpose has been served, it should be removed from the stomach with ease.
Over the last 3 decades, various approaches have been pursued to increase the retention of an oral dosage form in the stomach. These systems include: Bioadhesive systems, swelling and expanding systems, High density systems, Floating systems, Modified systems.
Fig: 2 Approaches to Gastric Retention:
The other approach is to alter the formulation's density by using either high or low-density pellets, so called altered density approach.
Here, the density of the pellets must exceed that of normal stomach and should be at least 1.40. In preparing such formulations, drug can be coated on a heavy core or mixed with heavy, inert materials such as barium sulfate, titanium dioxide, iron powder and oxide. The weighed pellet can then be covered with a diffusion controlled membrane.
While the system is floating on the gastric contents the drug is slowly released from the low density pellets or floating drug delivery systems (FDDS) and are also called as hydro dynamically balanced systems (HBS). FDDS or HBS have a bulk density lower than gastric fluid, that is, bulk density of less than one. HBS remains buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time and 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.
Shells of polymer with lower density than that of the gastrointestinal fluid, (ex polystyrene) have been used for this purpose. Swelling type dosage forms are such that on 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 as 'plug type system' since they exhibit tendency to remain logged at the pyloric sphincter. Modified shape systems are no disintegrating geometric shapes molded from silstic elastomer or extruded from polyethylene blends which extend the gastric retention time depending on size, shape and flexural modulus of the drug delivery system.
Unfortunately, most of these systems have many drawbacks. Floating system requires presence of food to delay their gastric emptying. They do not always release the drug at the intended sit. Bio-adhesive system adheres to the mucus. This adhesion is a result of electrostatic and H-bond formation at the mucus-polymer boundary. The bond formation is prevented by acidic environment and thick mucus present in the stomach.
1.5 Different Techniques in Gastric Retention 5,6, 7.:
A number of approaches have been used to increase the GRT of a dosage form in stomach by employing a variety of concepts. These include –
a) Buoyant/ Floating Systems:
Floating Drug Delivery Systems8 (FDDS) have a bulk density lower than gastric fluids and thus remain buoyant in the stomach for a prolonged period of time, without affecting the gastric emptying rate. 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. This results in an increase in the GRT and a better control of fluctuations in the plasma drug concentrations. Floating systems can be classified into two distinct categories, non-effervescent and effervescent system.
Fig: 3 Graphic of Buoyant tablet, which is less dense than the stomach fluid therefore it remains in the fundus.
b) Bio/Muco-adhesive Systems9, 10:
Bioadhesive drug delivery systems (BDDS) are used to localize a delivery device within the lumen to enhance the drug absorption in a site-specific manner. This approach involves the use of bioadhesive polymers, which can adhere to the epithelial surface in the stomach. A microbalance-based system is reported for measuring the forces of interaction between the GI mucosa and the individual polymers, and the Cahn Dynamic Contact Angle Analyzer has been used to study the adherence.5 Gastric mucoadhesion does not tend to be strong enough to impart to dosage forms the ability to resist the strong propulsion forces of the stomach wall. The continuous production of mucous by the gastric mucosa to replace the mucous that is lost through peristaltic contractions and the dilution of the stomach content also seems to limit the potential of mucoadhesion as a gastro retentive force. Some of the most promising excipients that have been used commonly in these systems include polycarbophil, carbopol, lectins, chitosan, CMC and gliadin, etc. Some investigators have tried out a synergistic approach between floating and bioadhesion systems. Other approaches reported include use of a novel adhesive material derived from the fimbriae (especially Type 1) of bacteria or synthetic analogues combined with a drug to provide for attachment to the gut, thereby prolonging the transit time, a composition comprising an active ingredient and a material that acts as a viscogenic agent (for example curdlan and/or a low-substituted hydroxypropylcellulose),
c) Swelling and Expanding Systems11:
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 long period of time. These systems may be named as “plug type system”, since they exhibit the tendency to remain logged at the pyloric sphincter if that exceed a diameter of approximately 12-18 mm in their expanded state. The formulation is designed for gastric retention and controlled delivery of the drug into the gastric cavity. A balance between the extent and duration of swelling is maintained by the degree of cross-linking between the polymeric chains. A high degree of cross-linking retards the swelling ability of the system maintaining its physical integrity for prolonged period.
d) High Density Systems:
These systems with a density of about 3 g/cm3 are retained in the rugae of the stomach and are capable of withstanding its peristaltic movements. A density of 2.6-2.8 g/cm3 acts as a threshold value after which such systems can be retained in the lower part of the stomach. High-density formulations include coated pellets. Coating is done by heavy inert material such as barium sulphate, zinc oxide, titanium dioxide, iron powder etc.
e) Incorporation of Passage Delaying Food Agents12:
Food excipients like fatty acids e.g. salts of myristic acid change and modify the pattern of the stomach to a fed state, thereby 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-C14.
f) Ion Exchange Resin13:
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. The 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, an exchange of chloride and bicarbonate ions take place. As a result 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.
g) Osmotic Regulated Systems:
It is comprised of an osmotic pressure controlled drug delivery device and an inflatable floating support in a bio-erodible capsule. In the stomach the capsule quickly disintegrates to release the intra gastric 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 controlled drug delivery device consists of two components – drug reservoir compartment and osmotically active compartment.
Many therapeutic agents ate metabolized in the upper GI tract into an active form. This active form is then through the wall intestine. The therapeutic agents ate metabolized by enzymes in the upper GI tract. If the therapeutic agent is present in large quantities, saturation of these enzymes can occur with the result that most of the therapeutic agent passes through the GI tract therefore limits the potency of the therapeutic agent.
Conventional controlled release dosage forms have a density greater than that of gastric contents, thus these dosage forms sink to the bottom of the stomach once ingested. The de novo design of oral controlled drug systems (DDS) is known in the art to achieve more predictable bioavailability of drugs. However, it is well known that conventional release DDS do not Overcome adversities such as gastric residence time (GST) and gastric empty time (GET). Gastric emptying is the process by the fasted stomach exhibits a cyclic activity called the inter-digestive migrating motor complex (IMMC). The purpose of this cycle is to migrate the contents of the stomach through the pyloric sphincter although ingestion of food interrupts the cycle.
One approach to overcome the adversities of GRT and GET is the floating system also known as hydrodynamically balanced systems. These systems are expected to remain lastingly buoyant on the gastric contents without affecting the intrinsic rate of emptying because their bulk density is lower than that of the gastric fluids. The floating forms maintain their low density value while the polymer hydrates and forms a gel. The drug is progressively release from the swollen matrix in the case of conventional hydrophilic matrices.
1.6 Types of Floating Drug Delivery Systems (fdds):
Floating drug delivery systems (FDDS) have a bulk density less than gastric fluids and so remain 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 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 the fluctuations in plasma drug concentration However, besides 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 the meal. To measure the floating force kinetics, a novel apparatus for determination of resultant weight (RW) has been reported in the literature. The RW apparatus (fig: 4) operates by measuring continuously the 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 variations
|
Fig: 4. Diagrammatic representation of RW apparatus.
Based on the mechanism of buoyancy, two distinctly different technologies have been utilized in development of FDDS, which are:
A. Effervescent System, and
B. Non- Effervescent System.
1.6.1. Effervescent System13, 14. :
Effervescent systems include use of gas generating agents, carbonates (ex. Sodium bicarbonate) and other organic acid (e.g. citric acid and tartaric acid) present in the formulation to produce carbon dioxide (CO2) gas, thus reducing the density of the system and making it float on the gastric fluid. An alternative is the incorporation of matrix containing portion of liquid, which produce gas that evaporates at body temperature.
These effervescent systems further classified into two types.
· Gas Generating systems
· Volatile Liquid/Vacuum Containing Systems.
I. Gas – Generating Systems:
1. Intra Gastric Single Layer Floating Tablets or Hydrodynamically Balanced System (HBS):
These are as shown in Fig. 5 and formulated by intimately mixing the CO2 generating agents and the drug with in the matrix tablet. These have a bulk density lower than gastric fluids and therefore remain floating in the stomach unflattering the gastric emptying rate for a prolonged period. The drug is slowly released at a desired rate from the floating system and after the complete release the residual system is expelled from the stomach. This leads to an increase in the GRT and a better control over fluctuations in plasma drug concentration.
GF: Gastric Fluid
Fig: 5 Intra Gastric Single Layer Floating systems.
2. Intra Gastric Bilayer Floating Tablets:
These are also compressed tablet as shown in Fig 6 and containing two layer i.e.,
i. Immediate release layer and
ii. Sustained release layer.
Fig: 6 Intra Gastric Bilayer Buoyant Tablet.
1. Multiple Unit type floating pills:
These systems consist of sustained release pills as ‘seeds’ surrounded by double layers (fig: 7). The inner layers consist of effervescent agents while the outer layer is of swellable membrane layer. When the system is immersed in dissolution medium at body temperature, it sinks at once and then forms swollen pills like balloons, which float as they have lower density. This lower density is due to generation and entrapment of CO2 within the system.
Fig: 715.
A multi-unit oral buoyant dosage system. Stages of floating mechanism: (A) penetration of water; (B) generation of CO2 and floating; (C) dissolution of drug. Key: (a) conventional SR pills; (b) effervescent layer; (c) swellable layer; (d) expanded swellable membrane layer; (e) surface of water in the beaker (370C).
II. Volatile Liquid / Vacuum Containing Systems16:
1. Intragastric Floating Gastrointestinal Drug Delivery System:
These systems can be made to float in the stomach because of floatation chamber, which may be a vacuum or filled with air or a harmless gas, while drug reservoir is encapsulated inside a microprous compartment, as shown in Fig.8
Fig: 8. Intra Gastric Floating Gastrointestinal Drug Delivery Device
2. Inflatable Gastrointestinal Delivery Systems:
In these systems an inflatable chamber is incorporated, which contains liquid ether that gasifies at body temperature to cause the chamber to inflate in the stomach. These systems are fabricated by loading the inflatable chamber with a drug reservoir, which can be a drug, impregnated polymeric matrix, then encapsulated in a gelatin capsule.
Fig no: 9. Inflatable Gastrointestinal Delivery System
After oral administration, the capsule dissolves to release the drug reservoir together with the inflatable chamber. The inflatable chamber automatically inflates and retains the drug reservoir compartment in the stomach. The drug continuously released from the reservoir into the gastric fluid. This system is shown in Fig. 9
3. Intragastric Osmotically Controlled Drug Delivery System:
It is comprised of an osmotic pressure controlled drug delivery device and an inflatable floating support in a biodegradable capsule. In the stomach, the capsule quickly disintegrates to release the intragastirc 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; drug reservoir compartment and an osmotically active compartment.
The drug reservoir compartment is enclosed by a pressure responsive collapsible bag, which is impermeable to vapour and liquid and has a drug delivery orifice. The osmotically active compartment contains an osmotically active salt and is enclosed within a semi permeable housing. In the stomach, the water in the GI fluid is continuously absorbed through the semi permeable membrane into osmotically active compartment to dissolve the osmotically active salt. An osmotic pressure is thus created which acts on the collapsible bag and in turn forces the drug reservoir compartment to reduce its volume and activate the drug reservoir compartment to reduce its volume and activate the drug release of a drug solution formulation through the delivery orifice.
The floating support is also made to contain a bio-erodible plug that erodes after a predetermined time to deflate the support. The deflated drug delivery system is then emptied from the stomach. This system is shown in Fig.10
Fig: 10. Intragastric Osmotically Controlled Drug Delivery System
1.6.2. Non-Effervescent Systems17:
This type of system, after swallowing, swells unrestrained via imbibition of gastric fluid to an extent that it prevents their exit from the stomach. These systems 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 methods 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 the outer gelatinous barrier. The air trapped by the swollen polymer confers buoyancy to these dosage forms.
Other approaches reported in the literature are hydro dynamically balanced (HBS) systems developed by Sheth and Tossounian, which contain a mixture of drug and hydrocolloids, sustained release capsules containing cellulose derivatives like starch and a higher fatty alcohol or fatty acid glyceride, bilayer compressed capsules, multilayered flexible sheet-like medicament devices, hollow microspheres of acrylic resins, polystyrene floatable shells, single and multiple unit devices with floatation chambers and microporous compartments and buoyant controlled release powder formulations, etc.
Fig: 11 swelling systems
Recent developments include use of superporous hydrogels that expand dramatically (hundreds of times their dehydrated form within a matter of seconds) when immersed in water. Oral drug delivery formulations made from the gels would swell rapidly in the stomach, causing medications to move more slowly from the stomach to the intestines and be absorbed more efficiently by the body.
These factors include density, size and shape of dosage form, concomitant intake of food and drug such as anti-cholinergic agents (e.g. Atropine, propantheline), opiates (e.g. Codeine) and prokinetic agents (e.g. Metoclopramide) and biological factors such as gender, posture, age, body mass index and disease state (e.g. Diabetes).
In order for a HBS dosage form to float in the stomach the density of the dosage form should be less than the gastric contents. However, the floating force kinetics of such dosage form has shown that the bulk density of a dosage form is not the most appropriate parameters for describing its buoyancy.
These are better represented and monitored by resultant weight measurements and swelling experiments. This is because the magnitude of floating strength may vary as a function of time and usually decreases after immersion of the dosage form into fluid consequently to the evolution of its hydro-dynamical equilibrium.
The prolongation of gastric residence time (GRT) by food is expected to maximize drug absorption form FDDS due to increased dissolution of drug and longer residence at the most favorable sites of absorption. GRT of a dosage form in the fed state can also be influenced by its size.
Most of the floating systems reported in the literature are single unit systems, such as floating tablets. These systems are unreliable and irreproducible in prolonging residence time in the stomach when orally administered owing to their fortuitous (all-or-nothing) emptying process. On the other hand, multiple unit dose forms appear to be better suited since they are claimed to reduce the inter subject variability in absorption and lower the probability of dose-dumping. It also eliminates the dependence of the drug effect on gastric emptying, the mini depots being sufficiently small to make possible their passage through pylorus even between its actual openings. As a result, the drug will reach the site of optimum absorption and a high local concentration will also be avoided.
1.7. MARKETED PRODUCTS OF FDDS18,19,20
Table: 1
|
SL.NO |
BRAND NAME |
DRUG (DOSE) |
COMPANY COUNTRY |
TECHNOLOGY |
|
1. |
Modapar® |
Levodopa (100mg), Benserazide (25mg) |
Roche Products, USA |
Floating CR capsule |
|
2. |
Valrelease® |
Diazepam (15 mg) |
Hoffmann-LaRoche, USA |
Floating capsule |
|
3. |
Liquid Gavison® |
Alhydroxide(95 mg), Mg carbonate (358 mg) |
GlaxoSmithKline, India |
Effervescent floating liquid alginate Preparation |
|
4. |
Topalkan® |
Al-Mg antacid |
Pierre Fabre Drug, France |
Floating liquid alginate preparation |
|
5. |
Conviron |
Ferrous sulphate |
Ranbaxy, India |
Colloidal gel forming FDDS |
|
6. |
Cifran OD® |
Ciprofloxacin (1 gm) |
Ranbaxy, India |
Gas-generating floating tablet |
|
7. |
Cytotec® |
Misoprostal (100 mcg/200 mcg) |
Pharmacia, USA |
Bilayer floating capsule |
|
8. |
Oflin OD® |
Ofloxacin (400mg) |
Ranbaxy, India |
Gas generating floating tablet |
|
9 |
Glumetza™ |
Metformin HCl |
Depomed,usa |
Acuform™ |
|
10 |
ProQuin® XR |
Ciprofloxacin hydrochloride |
Depomed,usa |
Acuform™ |
Drugs explored for various floating dosage forms:
Table: 2
|
Dosage Forms |
Drugs |
|
Microspheres |
Aspirin, Ibuprofen, Tranilast |
|
Granules |
Diclofenac sodium, Indomethacin, Prednisolone |
|
Capsules |
Diazepam, Furosemide, L-Dopa and Benserazide |
|
Tablets / pills |
Amoxycillin Trihydrate, Ampicillin, Diltiazem, p -Aminobenzoic acid, Riboflavin-5’-phosphate, Theophylline, Verapamil HCl |
ADVANTAGES OF FDDS:
Floating dosage systems form important technological drug delivery systems with gastric retentive behavior and offer several advantages in drug delivery. These advantages include:
1. Improved drug absorption, because of increased GRT and more time spent by the dosage form at its absorption site.
2. Controlled delivery of drugs.
3. Delivery of drugs for local action in the stomach.
4. Minimizing the mucosal irritation due to drugs, by drug releasing slowly at controlled rate.
5. Treatment of gastrointestinal disorders such as gastro-esophageal reflux.
6. Simple and conventional equipment for manufacture.
7. Ease of administration and better patient compliance.
Other advantages are:
As mentioned earlier, drug absorption from oral controlled release (CR) dosage forms is often limited by the short GRT available for absorption.
However, HBS type dosage forms can retain in the stomach for several hours and therefore, significantly prolong the GRT of numerous drugs. .
These special dosage forms are light, relatively large in size, and do not easily pass through pylorus, which has an opening of approx. 0.1– 1.9 cms.
A floating dosage form is a feasible approach especially for drugs which have limited absorption sites in upper small intestine. The controlled, slow delivery of drug to the stomach provides sufficient local therapeutic levels and limits the systemic exposure to the drug. This reduces side effects that are caused by the drug in the blood circulation. In addition the prolonged gastric availability from a site directed delivery system may also reduce the dosing frequency. The eradication of Helicobacter pylori requires the administration of various medicaments several times a day, which often results in poor patient compliance. More reliable therapy can be achieved by using GRDDS. Floating alginate beads have been used for the sustained release of Amoxycillin trihydrate. Thus, it can be expected that the topical delivery of antibiotic through a FDDS may result in complete removal of the organisms in the fundal area due to bactericidal drug levels being reached in this area, and might lead to better treatment of peptic ulcer.
As sustained release systems, floating dosage forms offer various potential advantages. Drugs that have poor bioavailability because their absorption is limited to upper GI tract can be delivered efficiently thereby maximizing their absorption and improving their absolute bioavalabilities.
Floating dosage forms with SR characteristics can also be expected to reduce the variability in transit performance. In addition, it might provide a beneficial strategy for gastric and duodenal cancer treatment.
The concept of FDDS has also been utilized in the development of various anti- reflux formulations. Floating systems are particularly useful for acid soluble drugs, drugs poorly soluble or unstable in intestinal fluids, and those which may undergo abrupt changes in their pH dependent solubility due to food, age and disease states.
LIMITATIONS:
1. The major disadvantage of floating system is requirement of a sufficient high level of fluids in the stomach for the drug delivery to float. However this limitation can be overcome by coating the dosage form with the help of bioadhesive polymers that easily adhere to the mucosal lining of the stomach.
2. Floating system is not feasible for those drugs that have solubility or stability problem in gastric fluids.
3. The dosage form should be administered with a minimum of glass full of water (200-250 ml).
4. The drugs, which are absorbed throughout gastro-intestinal tract, which under go firstpass metabolism (nifedipine, propranolol etc.), are not desirable candidate.
5. Some drugs present in the floating system causes irritation to gastric mucosa.
CONCLUSION:
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.
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Received on 01.07.2017 Modified on 15.07.2017 Accepted on 12.02.2018 ©A&V Publications All right reserved Research J. Science and Tech. 2018; 10(2): 145-156. DOI: 10.5958/2349-2988.2018.00022.0 |
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