A Review on Floating and Mucoadhesive Drug Delivery System

 

Mali Hanmant S.*, Dhadde Gurunath S., Sapate Rohit B., Gidde Nikita D., Bagade Priyanka V.

Department of Pharmaceutics, Rajarambapu College of Pharmacy, Kasegaon (MS) India 415404.

*Corresponding Author E-mail: 555hanamantmali@gmail.com

 

ABSTRACT:

The main goal of just about every drug delivery system is to supply preferred concentrations of drugs in blood and other body fluids, which would be clinically useful and non-hazardous for a long period of time. The Floating and Mucoadhesive both are coming under the novel drug delivery system in which they considered as predominantly more effective as compared to alternative drug delivery system because this formulation having direct contact with a biological system. The latest developments of FDDS and mucoadhesive including the biological and methodology factors that affect Gastrointestinal residence time, the main mucosal system which is explained, the structure of the main formulation described, approaches to develop single-unit and various different-unit floating and mucoadhesive systems, advantages, and one's categorization and development, in which the material used for floating mucoadhesive formulation preparation and other material which are shown on the rationale of their use in this formulation, aspects characterization are enlisted like Thickness and Diameter Testing, Bioadhesion Test, Drug Content Uniformity Test, X Rays Studies Water Uptake Studies, etc. This review also describes the studies to assess the effectiveness and implementation of floating systems, and applications of mucoadhesive systems.

 

KEYWORDS: Floating, Mucoadhesive, Gastro retentive, Bioadhesive, Effervescent, Colloidal system.

 

 


INTRODUCTION:

Oral route is one of the most convenient, predominant, and remains the preferable way to administer the medication. Oral drug delivery systems have been improved over the past two-three decades due to their considerable therapeutic benefits such as ease of administration, high degree of patient compliance, low cost of the therapy, and flexibility in formulation. It offers a predetermined, consistent, regulated rate of release of drugs, and draws considerable attention. However, due to the inadequate absorption or degradation of many drugs in the lower gastrointestinal tract (GIT), controlled dosage forms of release (CR) will be maintained in the upper GIT, preferably in the stomach, while the medications are delivered to the GIT region where they have been best absorbed.1, 2

 

The primary Drug delivery systems for controlled release (CRDDS) are gastro-retentive drug delivery systems (GRDDS), which are maintained as in stomach to a longer period of time, thereby aiding in drug absorption for the expected length. This in effect enhances bioavailability, decreases drug wastage, and increases the drug solubility that is somewhat soluble at high pH. There are several approaches used to retain the drug product in the stomach. These include bioadhesive, swelling and expanding systems, floating systems, altered form of systems and other delayed gastric emptying systems. The concept of buoyant preparation gives a convenient and effective approach to achieve enhanced gastric residence time (GRT) for drug delivery and prolonged drug action.3,4,5

 

Approaches to Gastric Retention:

Different kinds of methods have been developed to boost the Gastric retention time of formulations by incorporating variety of ideas as shown in Fig. 2. Such methods have been categorized on the basis of concept of gastric retention.6,7,8

·       Floating drug delivery systems (FDDS)

·       Bioadhesive systems

·       Swelling and expanding systems

 

1. Floating Drug Delivery Systems:

These are oral solid dosage forms (capsule or tablet) which are intended to sustain the time for the retention of the formulations inside the GI tract.9 This is a formulation of the drug as well as gel forming hydrocolloids intended to stay buoyant in stomach. This not only prolongs the time of GI residence, but also in a region of the Tract of GI that will increase drugs entering their Site of absorption in solution and being ready for absorption.10

 

Types

1. Non effervescent FDDS

2. Effervescent FDDS

 

Non-Effervescent systems:

It is also called as hydro dynamically balanced systems (HBS). They utilise Cellulose that is gel-forming or strongly swellable forms of hydrocolloids, polysaccharides as well as matrix forming polymers like polycarbonate, polyacrylate, polymethacrylate and polystyrene. The buoyancy to such formulation is provided by air trapped throughout the swollen polymer. When Non-Effervescent dosage forms come into contact with an aqueous medium, the hydrocolloid starts to hydrate by first forming a gel at the surface of the shape of the dosage.11 This gel form influences the speed of solvent-in diffusion and the drug substance come-out.

 

Fig. No. 1: Various Approaches to Gastroretentive systems

 

Fig. No. 2: Colloidal gel barrier systems

·       Colloidal gel barrier systems11, 12:

Based upon this principle, a bilayer tablet containing one immediate release and other sustained release layer can be prepared. Immediate release layer supplies the initial dosage while the other layer retains gastric fluid and forms the barrier of a colloidal gel at its surface.13 A multi-layer, adaptable, Sheath-like, gastric juice buoyant system demonstrating sustained release characteristics have also been established. This device is At least one was composed of dry self-supporting carrier film, made up of hydrophobic polymer matrix containing drug in either decentralised or dissolved forms as well as a barrier film overlaying the carrier film. A like carrier films and barrier films are enclosed all over their perimeter in such a way that they absorb a multitude of small air pockets which attribute to laminated films becoming buoyant.14,15

 

·       Micro porous compartment system

In this type of networks, drug reservoir is enclosed in a micro Porous Pore Compartment across its inner and outer surfaces. To avoid any direct interaction of gastric mucosal surface, the external The drug reservoir compartment walls are tightly enclosed. In stomach, the entrapped air of buoyancy chamber causes the delivery system to bounce over the gastric contents. Gastric fluid enters the system via the pores, dissolves the drug and delivers the dissolved drug for consistent transfer for absorption, across the intestine.

 

·       Alginate beads16:

·       Hollow Microspheres17:

 

Fig. No. 3: Micro porous compartment system

 

Fig. No. 4: Alginate beads system



Fig. No. 5: Formulation of hollow microspheres.

 

Effervescent systems:

By adding a floating chamber which can be filled with vacuum, air, or inert gas, It's possible to make a drug delivery system float in the intestine.18 By volatilization of the Organic solvent or reaction between organic acids and bicarbonate by effervescent salts, gas may be added to the floating chamber.

 

·       Volatile liquid containing systems:

Osmotically operated floating systems are these units. This comprises a deformable, hollow unit that can be transformed to after a prolonged time from a collapsed position to an enlarged position and restored to the collapsed position. The deformable device consists of two chambers divided by an impermeable bladder, which is pressure-responsive and mobile. (Fig. No. 6).19 In the first chamber, the drug is filled, and the volatile liquid is applied to the second chamber. The pump inflates upon administration and the drug is constantly discharged into the gastric fluid from the tank. This dissolves gradually, allowing after a predetermined time, the inflatable chamber would release gas and fall to allow the inflatable device to be spontaneously expelled from the stomach.20 An osmotic drug delivery mechanism powered by friction and an inflatable floating support consists of an intra-gastric, osmotically controlled drug delivery system in a bioerodible capsule. (Fig. No. 7)

 

·       Gas generating systems:

Effervescent materials that gasify at body temperature such as sodium bicarbonate, tartaric acid and citric acid or liquid-containing chambers. For the preparation of these systems, firstly resin beads are loaded with bicarbonate and then coating with ethyl cellulose is done.22 This coating is insoluble in water but allows permeation of water through it. This causes liberation of carbon dioxide because of which beads float in the stomach. The drug release process is shown to in Fig. No. 6. In that (A) Penetration of water (B) Generation of CO2 and floating (C) Dissolution of drug.

 

Fig. No. 6: Stages of floating mechanism

 

Fig. No. 7: Raft system

 

·       Raft systems:

Raft forming systems 16 incorporate alginate gels. These have a carbonate component that further to the reaction with gastric acid form bubbles in the gel and thus enables floating. The method adopted in rafting requires the generation of viscous compact gel in contact with gastric fluids, where each part of the liquid swells into a continuous sheet called a raft (Fig. No.7).23

 

Mucoadhesive Drug Delivery System:

Mucoadhesive drug delivery systems are delivery systems which use the bioadhesion property of other polymers that are sticky on hydration and therefore can be used for extended periods of time to direct a drug to a particular area of the body Bioadhesion is an interfacial process where two materials are forced together by interfacial forces, at least one of them seem to be biological. The bonding, like adhesion between that polymer and a biological membrane, would be between an artificial substance and a biological substrate. The term "mucoadhesion" has been used in the scenario of polymer which is attached to the mucin layer of a mucosal tissue.24,25 Mucoadhesive drug delivery systems can be delivered by various routes:

 

·       Buccal delivery system

·       Rectal delivery system

·       Oral delivery system

·       Nasal delivery system

·       Vaginal delivery system

·       Ocular delivery system

 

Theories of Mucoadhesion:

There are six general theories of adhesion, which have been adapted for the investigation of mucoadhesion:

 

1.      Electronic theory

2.      Mechanical theory

3.      Diffusion theory

4.      Adsorption theory

5.      Wetting theory

6.      Facture theory

Mechanisms of Mucoadhesion:

Mucoadhesion is the mechanism of typically split into two stages,

 

1. Contact stage:

2. Consolidation stage:

The first stage is marked by the contact of the mucoadhesive as well as the mucous membrane, the spreading and swelling of a formulation and the initiation of its deep contacts with the layer of mucus. In certain examples, such as vaginal or ocular formulations, in other cases the delivery mechanism is mechanically related, the deposition is enhanced by the aerodynamics of the organ to the membrane and the system, including the nasal path, is administered. The mucoadhesive substances are caused by the presence of moisture in the consolidation stage. The system is plasticized by humidity, allowing the mucoadhesive molecules to break free and pair up with weak van der Waals and hydrogen bonds as well.       

 

Essentially, there are two theories explaining the consolidation step:

1.     The diffusion theory

2.   The dehydration theory.26

 

As per diffusion theory, by interpenetration of their chains as well as the formation of secondary bonds, the mucoadhesive molecules and the glycoproteins of mucus interact jointly. The mucoadhesive system has characteristics that favour chemical as well as mechanical interactions for it to take effect. As per dehydration concept, substances which are able to readily gasify in an aqueous medium, while come in contact with the mucus can affect its dehydration due to the change of osmotic pressure.

 

Advantages of FBDDS:

·       Prolongs the retention time of a dosage form only at site of absorption, thus the increases the bioavailability.

·       Excellent accessibility, rapid onset of action.

·       Rapid absorption because of enormous blood supply and good blood flow rates.

·       Drug is protected from degradation in the acidic environment in the git.

·       Improved patient compliance.27

·       The FDDS are beneficial for drugs absorbed via the stomach eg: Ferrous salts, Antacids. Owing to increased GRT and much more time spent on the dosage form at its absorption site, improved therapeutic absorption.28

·       Treatment of gastrointestinal disorders like gastro esophageal reflux.

 

Disadvantages of Fbdds:

·       The development of local ulcerative symptoms due to prolonged drug interaction with ulcerogenic properties.

·       One of key constraints in the advancement of oral mucosal delivery is the lack of a good model for that in vitro screening to categorise drugs suitable for these administration.

·       Eating and Drinking is prohibited.27

 

Formulation of Fbdds:

The formulation of floating and mucoadhesive drug delivery system consist of Active drug, Polymer, Gas forming agent, Diluent, Glident, etc.

 

Factors affecting FBDDS33


Table No. 1: Factors affecting FBDDS.

Factors

Properties

Comments

physical factors

Density

The density should be smaller than the gastric content of the dosage type. (1.004gm per ml)

size and shape

This having inverse proportion size

Molecular weight

With the molecular weight of the polymer, the mucoadhesive force increases, up to 1, 0000, but there is no more impact beyond this amount.

Flexibility of polymer chain

For interpenetration and enlargement, versatility is a significant factor.

Environment related factors

pH

On the surface of both the mucus and the polymers, pH affects the charge.

Initial contact time

As the initial contact time increases, the mucoadhesive intensity increases.

Swelling

Swelling depends on the concentration of all polymers and on the presence of water.

Physiological Variables

Mucin Turn Over

The mucin turnover is expected to restrain the mucoadhesive retention time upon on mucus layers.

Diseased State

Mucin turnover results in significant amounts of solubilised mucin molecules. Physicochemical characteristics of mucus are required to affect during diseased states, like common cold, gastric ulcers, ulcerative colitis and cystic fibrosis, bacterial.

Nature Of Meal

Feeding of indigestible polymers of fatty acid salts could also alter the motility pattern of a stomach to a fed state, thereby decreasing the gastric emptying and prolonging the release profile.

 


Active drug32

For the FBDDS system drug should having Narrow absorption window in GI tract, Primarily absorbed from stomach and upper portion of GI tract, act in the stomach locally, induce colon deterioration and interact with normal colonic bacteria.

 

Mucoadhesive Polymer:

There are two major classifications of hydrophilic polymer and hydrogels of mucoadhesive polymers. The strongest mucoadhesive properties, polyvinyl pyrrolidone (PVP), methyl cellulose (MC), sodium carboxy methylcellulose (SCMC), hydroxy propyl cellulose (HPC) and another cellulose derivative are seen in the broad groups of hydrophilic polymers containing the carboxylic community.

·       Anionic group- Carbopol, Polyacrylates and their cross-linked modifications

·       Cationic group- Chitosan and its derivatives

·       Neutral group- Eudragit- NE30D etc

 

Characteristics of an Ideal Mucoadhesive Polymer:

1.     The polymer and its metabolic by products should be non-toxic and not absorbable from the GI tract.

2.     It should be non-irritant to either a mucus membrane.

3.     Ideally, this should form a tight no-covalent bond with the surfaces of mucin-epithelial cells.

4.     It should allow the medication to be integrated directly and should provide no impediment to its release.

5.      Polymers do not decompose during storage or during the shelf life of the dosage form.


 

Table No. 2: Examples of some Mucoadhesive polymers

Natural

Na alginate, Pectin, Tragacanth, Gelatin, arginine

Synthetic

Polyvinyl alcohol, Polyamides, polycarbonates, Polyalkylene glycols, Polyvinyl ethers, Esters and halides, Polymethacrylic acid, Polymethyl methacrylic acid, Methylcellulose

Biocompatible

Esters of haluronic acid, Polyvinyl acetate, Ethylene glycol

Biodegradable

Poly (lactides), Poly (glycolides), Poly (lactide-co-glycolides), Polycaprolactones, Polyalkyl cyanoacrylates. Polyorthoesters, Polyphosphoesters

 


Other ingredients such as gas generating agent, diluent, glidant, in most of formulation the gas generating agent is used as sodium bicarbonate, citric acid. The diluent is used as lactose, micro crystalline cellulose, PVP K30, sorbitol, etc. the glidants used in this formulation are magnesium stearate, starch, talc, etc.

 

Evaluation of Mucoadhesive Dosage Forms:

In vitro tests / ex vivo 29

 

·        Methods of determining tensile strength

·      Falling process of liquid film

·        Methods of assessing shear pressure

·      Colloidal process of staining of gold

·        Method of Adhesion Weight

·      Method of Viscometer

·        Method of fluorescent probes

·      Process of Thumb

·        Method of flow channel

·      Number of Adhesion

·        Mechanical method for spectroscopic

·      Electrical conductance

·        Swelling characteristics

 

 

In vitro drug release studies30

·       Mucoretentability studies

·       Use of pharmacoscintigraphy

·       Use of radioisotopes

·       Usage of oximetry for electron paramagnetic resonance (EPR)

·       Use of gamma scintigraphy

·       Studies on X rays

·       Isolated loop technique

 

 

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Received on 03.02.2021            Modified on 03.04.2021           

Accepted on 05.05.2021      ©Asian Pharma Press All Right Reserved

Asian Journal of Pharmacy and Technology. 2021; 11(3):225-230.

DOI: 10.52711/2231-5713.2021.00037