Natural Mucilage-Based Floating Drug Delivery Systems: Formulation Strategies, Mechanisms, and Applications

GRDDS constitute an emerging technology in oral drug delivery that seeks to improve the residence time of oral dosage forms in the stomach and augment bioavailability of drugs and their therapeutic action. They are particularly effective when the absorption time of the drug in the upper gastrointestinal tract is short, it is insoluble at alkaline pH or acts locally in the stomach.[1] One of the GRDDS technologies which has attracted a lot of interest is floating drug delivery systems (FDDS) because of their potential to stay afloat on gastric fluids, thereby increasing the gastric retention time without disrupting normal gastric emptying. FDDS work through their low density relative to gastric contents to enable them to float to the surface releasing the drug in a controlled way.[2] The necessity of floating systems can be explained by the fact that traditional oral drug forms have several shortcomings, including unpredictable emptying of the stomach, which results in low absorption of drugs and variable plasma drug levels. FDDS overcome these issues by enhancing the solubility of drugs, reducing drug waste, and producing a prolonged release of drugs in the stomach. [3]

Traditionally, synthetic polymers such as hydroxypropyl methylcellulose (HPMC) and carbopol have been widely used in FDDS formulations. Nevertheless, these types of polymers have a number of drawbacks, such as the possibility of toxicity, high price, environmental impact, and non-biodegradability. Other problems like irritation caused by polymer and regulatory limitations have also prompted the search of less toxic options. [4] Natural mucilage is a promising alternative in recent years because of its biocompatibility, biodegradability, non-toxicity, and cost-effectiveness. Mucilage is a polysaccharide that is extracted by plants (seeds, leaves, and roots) and has excellent swelling, gel-forming, and drug-releasing characteristics, thus highly applicable in floating drug delivery. [5] Moreover, natural mucilage-based systems are eco-friendly, provide patients with compliance, and enhance therapeutic performance, which has been attracting more and more research in pharmaceuticals. Such materials would serve as an efficient matrix forming agent, binders, and release retardants and help to develop effective floating drug delivery systems. [6]

2. Overview of Floating Drug Delivery Systems

2.1 Definition and Concept

Floating Drug Delivery Systems (FDDS) is a gastro-retentive system, a system that assists in increasing the gastrointestinal retention of dosage in the gastric fluids. They also have lower bulk density than gastric contents (average of 1.004 g/cm 3) and therefore are able to ascend to the surface of the stomach without being forced out of the pylorus. [7].The basic principle of FDDS lies in the possibility of attaining the controlled release and the sustained release of drugs and the dose form is located in the stomach.[8] The system is then either made to give out gas, or it swells to reduce the density to allow the system to be retained suspended and then the drug to be introduced at a regulated rate after administration. [8]   After administration, the system is either made to produce gas or it swells to decrease the density so that it can be kept suspended and the drug could be delivered at a controlled rate. This is particularly applicable in drugs that have a site-specific absorption in the upper gastrointestinal tract or labile in the presence of the intestinal conditions. [9].

2.2 Advantage and Limitations

Advantages

Floating Drug Delivery Systems have a number of therapeutic and formulation benefits:

• Increased gastric retention time and subsequent rise in drug bioavailability [10].
• Constant and slow drug release, decreasing dosing rate.
• Enhanced absorption of drugs having narrow absorption indices.
• Localized effect of drugs in the stomach, useful in gastric disorder.
• Less fluctuation in plasma concentration, enhancing patient compliance.
• Reduced wastage of drugs, particularly those that are not well soluble.

Limitations

In spite of their benefits, FDDS have some limitations as well:

• Reliance on the amount of gastric fluid, which can be different in patients.
• Inappropriateness to drugs that result in gastric irritation.
• Variability in gastric emptying time, affecting system performance
• Not suitable in drugs that are very soluble in acidic pH.
• Problems with providing consistent buoyancy to all recipes.
• There is the possibility of dumping the dose in the case of a system failure [11].

2.3 Classification of Floating Drug Delivery Systems

It is generally grouped into effervescent and non-effervescent systems, depending on how they reach their goal of buoyancy.

2.3.1 Effervescent Systems

Effusive systems are based on the production of gases (typically CO 2) in the effort to create buoyancy. The gas generating agents often include Sodium Bicarbonate, citric acid or tartaric acid and are commonly found in some system.

Mechanism:

• When it comes into contact with gastric fluid it reacts with an acid-base reaction.
• CO₂ is generated and gets trapped within the polymer matrix
• The System is made less dense and comes to rest.

Types:

• Gas-generating tablets
• Volatile liquid-containing systems

Critical aspect

• Short floating lag time (rapid floating initiation)
• Appropriate in sustained release preparations.

Systems of the effervescent type are highly utilized as they are simple and effective to gain an immediate buoyancy [12].

2.3.2 Non-Effervescent Systems

Non-effervescent systems have no dependence on the generation of gases; they make use of swelling and geling polymers to ensure buoyancy.

 Mechanism:

•      Gastric fluid is absorbed by hydrophilic polymers.

•      There is swelling, and a gel barrier is created.

•      The system becomes lower in density and floats.

Types:

Hydrodynamically balanced systems (HBS).

•      Swelling systems

Floating beads and microspheres.

•      Alginate-based systems

Critical aspect:

• Longer floating duration
• Stabilized and predictable performance.
• Superset in natural mucilage preparations.

They are especially beneficial when natural polymers like mucilage are used because they are good in swelling and forming matrices [13].

Mechanism of Floating Systems.

3.1 Buoyancy Principle

The basic principle underlying Floating Drug  Delivery  System (FDDS) is the law of buoyancy where the dosage form floats on gastrointestinal fluid, because it is less dense than the stomach contents. Archimedes principle states that the upward forces of buoyancy of a body immersed in a fluid is equal to the weight of the fluid that it displaces. In the case where the upward force is greater than the force of gravity on the dosage form, it floats [14].

Polymers and gas-generating agents are added to FDDS to make sure that dosage form buoyed over a period of time. This increases the gastric absorption of drugs and boosts bioavailability, particularly in drugs having narrow absorption window [15].

3.2 Density Reduction

One of the key factors to floatation is density reduction. The density of the system should be less than that of the stomach fluid (~1.004g/cm³). This is possible in various mechanisms in accordance to the type of formulation:

•           Effusive systems: A carbon dioxide gas is produced through acid-base reactions (e.g., Sodium Bicarbonate and Citric acid), and traps within the polymer matrix, reducing density.

•           Non-effervescent systems: Swelling polymers are used, which increase in volume but not mass due to being moistened.

This increases the density so that the dosage form can be floated and remain in the stomach during prolonged durations of time [16]. Additionally, there should be ideal density/structural integrity ratio to prevent premature sinking or breaking. [17].

3.3 Swelling and Gel Formation

Gel formation and swelling are key factors in non-effervescent floating systems. The polymers, including natural mucilage, are hydrophilic and absorb the gastric fluid and hydrate rapidly, which results in:

• Swelling of the polymer matrix
• Development of a gel barrier of a viscous gel.
• Cavities filled by air in the matrix.

Such a swollen gel structure does not only help in the buoyancy but also regulates drug release by providing a diffusion barrier. Floating behavior and the rate of drug release depend on the rate of swelling and gel strength [18].

The natural mucilage is especially beneficial in this mechanism because it has a high water-binding capacity and a strong gel-forming ability, thus being suitable in sustained-release floating formulations [19].

Figure 1: Mechanism of floating drug delivery system

Figure 2: Classification of Floating Drug Delivery Systems

Figure 3: A Schematic Representation of Buoyancy Mechanism.

4. Natural Mucilage: Sources and Properties.

4.1 Definition of Mucilage

Mucilage is a designation of a group of natural, high-molecular-weight polysaccharides, obtained mostly by means of plants, that are solutions that are viscous and gel-like when wet. They are normally made up of complex carbohydrates that include arabinose, galactose, rhamnose and uronic acids, which make them very good in water binding and swelling [20].

Mucilage is a very popular polymer in the manufacturing pharmaceutical industry as a binder, thickening agent, stabilizer, and controlled-release polymer, especially in gastroretentive drug delivery systems because it is biocompatible, non-toxic and eco-friendly [21].

4.2 Sources of Natural Mucilage.

Natural mucilage is mostly obtained of vegetable origin, particularly seeds, leaves, roots, and bark. These are renewable, cheap, and are common materials that make them appealing as an alternative to synthetic excipients.

Plant-Based Sources

Fenugreek

• Scientific name: Trigonella foenum-graecum.
• Aggalactomannan polysaccharides-rich.
• Both exhibited a high swelling index and viscosity.
• Most commonly used in sustained release preparations.

 Okra

• Scientific name: Abelmoschus esculentus.
• Contains acidic polysaccharides
• Good film-forming and binding properties.
• Floating and matrix tablet compatible.

 Flaxseed

• Scientific name: Linum usitatissimum.
• Neutral and acidic polysaccharides.
• Good water retention and gel-forming properties.
• Application in controlled-release systems.

Increasingly, these mucilages produced by plants are used in floating drug delivery system due to their natural source, safety, and multifunctional characteristics [22].

4.3 Physicochemical Characteristics of Mucilage.

Mucilage physicochemical properties control its performance in floating drug delivery systems:

4.3.1 Swelling Index

Swelling index is a scale of the ability of mucilage to take in water and swell. When mucilage comes in interaction with stomach fluid it hydrates and swells to form a gel-like matrix that contributes to:

•           Decrease in system density.

•           Enhanced buoyancy

•           Controlled drug release

The desirable swelling index is high to increase the duration of gastric retention and continuous drug delivery [23].

 4.3.2 Viscosity

Viscosity is an indicator of thickness and resistance to flow of mucilage solutions. It is important in:

•           Creation of a powerful gel shield.

•           Drug diffusion control

•           Stability of the dosage form

Higher viscosity mucilage is also more effective at release retardation and matrix integrity, and therefore is appropriate in floating formulations [24].

4.3.3 Biodegradability

Natural mucilage is biodegradable by nature, meaning that it can be decomposed by the biological process into non-toxic residues.. This property ensures:

• Minimal toxicity and safety.
• Environmental sustainability
• Biocompatibility.

Biodegradability is a significant advantage over synthetic polymers, particularly in the development of environmentally benign pharmaceutical preparations. [25].

Table 1: Sources of Natural Mucilage and Their Biological Origin

Table 2: Physicochemical Properties of Natural Mucilage Used in FDDS

5. Extraction and Purification of Mucilage

5.1 General Extraction Process

Natural mucilage extraction of plants is a series of standardized operations aimed at extracting water soluble polysaccharides, with minimum contaminants. It is typically triggered by plant material (seeds, leaves or bark) cleaning and drying, and a reduction in size to expand surface area to be extracted. The fine material is impregnated or sprayed in distilled water, then the fine material is stirred or heated mechanically to stimulate the release of mucilage to the water medium [26].The wet extract is filtered with muslin cloth or centrifuged in order to isolate the insoluble residues, to obtain a crude mucilage solution. Organic solvents such as ethanol, acetone or isopropyl alcohol are then added to the solution to be precipitated in an approximately 1:2 or 1:3 mixture to isolate mucilage and soluble impurities. The precipitated mucilage is gathered, washed and dried in controlled conditions (40 50 C) and then milled and sieved to become a fine powder which can be taken in pharmaceutical preparations. [27].

5.2 Purification Techniques

To purify mucilage, it needs to be removed to remove potential contaminants (proteins, pigments and inorganic materials) that may affect its functionality and stability. A number of techniques are used:

• Solvent precipitation: This is a technique that is usually used as the first step in purification, and the solution is dissolved in alcohols [28].
• Centrifugation: Suspended impurities are eliminated and Clarity of the mucilage suspension enhanced.
• Dialysis: Eliminates low molecular weight impurities such as salts and sugars
• Enzymatic treatment: The unwanted biomolecules are degraded by the use of proteins or amylases.
• Activated charcoal treatment: Removal of pigments, increases intensity of color and purity.

Developed purification procedures, including ultrafiltration and chromatography procedures are also used to achieve highly purified mucilage to be used in special pharmaceutical purposes [29].

5.3 Effects of Factors on Yield of Mucilage.

The quality and quantity of extracted mucilage will depend on the different physicochemical and process-related parameters:

1. The type of the plant material is: oak bark.

• Type, maturity and storage of the source of the plants - The conditions have a great impact on the yield.
• Seed Generally, the mucilage content of seeds is higher as compared to leaves or bark.

2. Extraction Medium

• pH and type of solvent affect solubility and extraction efficiency
• Water is ideal, but acidic or alkaline soils can increase yield.

3. Temperature

• Mid temperature heating enhances extraction.
• Excess heat: This can destroy polysaccharides.

4. Extraction Time

• Soaking time adequately enhances mucilage release.
• Prolonged extraction may lead to degradation

5. Precipitation Solvent Ratio.

• High solvent ratios increase recovery but can impact on purity.

6. Drying Conditions

• Functional properties are maintained with controlled drying.
• High temperatures could decrease the ability to swell and viscosity.

These factors are essential to optimize to achieve maximum yield, purity, and functionality of mucilage in FDDS [30].

Figure 4: Flowchart of Mucilage Extraction and Purification Process

6. Use of Natural Mucilage in FDDS.

The natural mucilage plays a very significant multipurpose role in FDDS, due to its unusual physicochemical properties of hydration capacity, gel formation and biocompatibility. These characteristics enable mucilage to be an effective polymer in controlling the properties of buoyancy and drug release.

6.1 Swelling Behaviour

One of the most effective function of natural mucilage in FDDS is swelling. When mucilage comes in interaction with stomach fluid, it absorbs water quickly and volumetric expansion occurs. This swelling causes:

• Reduction in density of the dosage form
• Enhanced buoyancy
• Extended gastric retention time.

The swelling phenomenon varies with the polymer structure, level of hydration and the environmental pH. Very swellable mucilage creates a moist outer layer that enables the system to stay afloat over long durations [31]. Also, swelling is involved in the establishment of a diffusion barrier that controls the release of drugs [32].

6.2 Gel Formation

The presence of hydrophilic polysaccharides makes natural mucilage have an excellent gel-forming ability. When hydrated, such polymers create a sticky and adhesive gel layer surrounding the dosage form.

This gel layer has a variety of purposes:

•           Functions as a shield against erosion.

•           Ensures the structural soundness of the formulation.

•           Gastric penetration of the fluid.

The gel layer strength and consistency have a profound effect on floating behavior and kinetics of drug release. A firmer gel guarantees longer retention and extended release [33].

6.3 Matrix Formation

Mucilage is a matrix-forming agent in floating systems, as it creates a three-dimensional network surrounding the drug. This matrix:

• Gives mechanical strength to the dosage form.
• Stops the breakdown of gastric fluid.
• Regulates diffusion routes of drugs.

The matrix system enables the drug to be uniformly distributed and gives a consistent release profile. Mats based on natural mucilage are especially beneficial, as they are biodegradable and non-toxic [34].

6.4 Drug Release Retardation

The retarded release of drugs is one of the most important functions of mucilage in FDDS, as it allows the drug to have prolonged therapeutic effect. This is achieved through:

• Formation of a gel barrier slowing diffusion of drugs.
• Higher viscosity, impeding the movement of drugs.
• Regulated dissolution of the polymer structure.

The release of drugs through mucilage-based systems typically goes through either diffusion-controlled or anomalous transport. Polymer concentration, viscosity, and cross-linking degree can be adjusted to control the release rate [35].

Natural mucilage is particularly effective in the maintenance of drug delivery because of their high water retention and gel stability, which is suitable with once-daily formulation.

7. Floating Drug Delivery System Strategies of Formulation.

The choice of approaches to formulate floating drug delivery systems (FDDS) can vary with the dosage form, drug properties, and desired release profile. Of these, floating tablets, beads, microspheres and gels have been extensively investigated because they are effective in improving gastric retention and controlled drug delivery.

7.1 Floating Tablets

The most widely used FDDS is floating tablets as it is simple and easy to produce. Such systems are typically ready-to-wear by direct compression or wet granulation methods involving use of hydrophilic polymers and gas generating substances.

 Mechanism:

• CO 2 is formed by effusive agents (e.g., Sodium Bicarbonate)
• Gas gets enclosed in the hydrated polymer matrix
• Tablet density decreases → floats on gastric fluid

 Advantages:

• Single formulation and easy scalability.
• Suitable to sustained-release drugs.
• Good patient compliance

Natural mucilage floating tablets have improved swelling and gelation, enhancing buoyancy and control of drug release [36].

7.2 Floating Beads

Multi-particulate systems of floating beads are usually prepared by ionotropic gelation methods. Beads can be produced by dropping natural polymers (e.g., alginate, mucilage) into cross-linking solutions (e.g., calcium chloride).

 Mechanism:

• Porous, low-density, beads formed.
• Trapping of air or gas in the matrix.
• Beads are suspended and give out drug slowly.

 Advantages:

• Even distribution of the stomach.
• Less chance of dose dumping.
• Increased control of drug release.

The efficacy of floating beads that have been prepared with natural mucilage in the context of better buoyancy and encapsulation is evidenced [37].

7.3 Floating Microspheres

Floating microspheres (synonymous with hollow microspheres or microballoons) are low-density, hollow, round particles formed by packaging a gas or liquid inside, and are expected to be buoyed temporarily over extended times.

 Preparation Techniques:

• Solvent evaporation
• Emulsion solvent diffusion
• Spray drying

 Mechanism:

• Formation of hollow internal structure
• Lower density allows floatation.
• Drug diffused and eroded through polymer.

 Advantages:

• Long gastric residence time.
• Regulated and predictable release of drugs.
• Enhanced bioavailability

Microspheres made of natural mucilage offer good biocompatibility and prolonged release properties [38].

7.4 Floating Gels

Floating gels are in situ gelling systems, which change to sol-to-gel in the stomach. These systems are specifically applicable when it comes to liquid formulations.

 Mechanism:

• Liquid formulation is changed to a gel when it is in contact with gastric pH or ions.
• Floating is possible through generation of gases or polymer swelling.
• Drug release is controlled by gel matrix.

 Advantages:

• Appropriate to use in children and elderly.
• Easy administration
• Uniform drug distribution

Gels made of natural mucilage have high gelation and viscosity and are a good choice in gastro-retentive applications [39].

Figure 5: Different Formulation Approaches of Floating Systems

Table 4: Formulation Techniques and Their Characteristics

8. Floating Drug Delivery Systems-Evaluation Parameters.

The analysis of Floating Drug Delivery systems (FDDS) is vital in determining the flow characteristics, floating behavior, and controlled drug release characteristics. These parameters are categorically divided into pre-compression and post-compression studies.

8.1 Pre-compression Parameters

Investigations Before the formulation of the tablets, pre-compression studies are conducted to determine the flow ability and compressibility of the blended powder.

 8.1.1 Bulk Density

The ratio of the mass of powder to the bulk volume including the spaces between particles is known as bulk density.

Significance:

• Shows the packing capacity of powder.
• Affects uniformity of weight of tablets.
• Affects compressibility

Reduced bulk density is beneficial to floating systems because it helps decrease the overall density of the dosage form [40].

 8.1.2 Angle of Repose

Angle of  repose is an assess of flowability  the powder that is the maximum angle of a pile of powder between the upper surface of the pile and the horizontal plane.

Significance:

• Denotes flow habits of powder.
• Helps in predicting uniform die filling

A value that is lower than 30 degrees in angle of repose implies good flow properties, which is a requirement to make uniform pill formulations [41].

8.2 Post-compression Parameters

The post-compression tests measure of the final dose form, particularly its floating capability and drug release properties.

 8.2.1 Floating lag time (FLT)

Floating lag time is the time of occurrence of the dosage form to ascend to the top of the gastric fluid following the administration.

Significance:

• Suggests efficiency of buoyancy.
• Short FLT (less than 1 min) is good.

FLT is based on the production of gases, the hydration of polymers, and the density of pills [42].

 8.2.2 Total Floating Time (TFT)

Total Floating Time is the time that the dosage form will stay on the surface of the gastric fluid.

Significance:

• Gastric retention ability.
• Longer TFT guarantees a longer drug release.

The optimal FDDS must be able to stay buoyant over a minimum of 12 hours to promote a lasting therapeutic effect [43].

 8.2.3 Drug Release Profile

Drug release profile are done to determine the rate and extent of drug kinetics of the floating system with time.

Methods:

• Dissolution testing with USP equipment.
• Regular sampling.

Kinetic Models:

• Korsmeyer-peppas model
• First order release
• Zero order
• Higuchi model

The release profile aids in identifying whether the formulation results in controlled or sustained drug delivery. The formation of gel barriers in natural mucilage-based systems tends to cause diffusion-controlled release [44].

Table 5: Evaluation Parameters for Floating Drug Delivery Systems

9. Uses of Floating Drug Delivery Systems.

The floating drug delivery system (FDDS) has become of significant significance in pharmaceutical studies because of their capability to rise the gastric residence time as well as enchance the efficacy of the drugs. They are especially applicable with drugs that need site-specific absorption, location gastric effect, or a greater bioavailability.

9.1. Drugs with Narrow Absorption Window.

Drugs have a narrow absorption window (NAW), which implies that they are mainly absorbed in the upper section of the gastrointestinal tract like the stomach or proximal small intestine. Traditional dosage forms do not have enough residence time in this region, and thus, the drug is not absorbed completely.

FDDS can address this shortcoming by holding the dosage form in the stomach longer, and in the process ensuring that the drug can be released at its optimum absorption point. This leads to:

• Enhanced drug absorption
• Reduced dosing frequency
• Improved therapeutic efficacy

Such drugs are levodopa, riboflavin and furosemide. The floating systems are a major way of enhancing their bioavailability by avoiding premature passages to the lower gastrointestinal tract (Huang et al., 2022)[45].

9.2 Local Stomach Action

FDDS are most useful with drug that are meant to have local therapeutic effect in the stomach, e.g., in the treatment of gastric ulcers, gastritis and infections with Helicobacter pylori.

FDDS allow the drug to have a long-term contact with the gastric mucosa resulting in:

• Increased local drug concentration.
• Improved therapeutic outcomes
• Less side effects in the system.

As an illustration, antibiotics and antacids that are a floating system exhibit a greater efficacy against gastric infections because of a longer residence time [46].

9.3 Improved Bioavailability

Another most notable use of FDDS is in increasing bioavailability, especially of drugs that exhibit:

• Poorly soluble at intestinal pH.
• Unstable in alkaline environments.
• Extensive first-pass metabolism

FDDS offer a controlled release environment, which enhances the absorption and dissolution of drugs by keeping the drug in the stomach. This results in:

• Raised plasma concentration of drug.
• Less variable absorption of drugs.
• Improved therapeutic efficiency

FDDS based on natural mucilage are particularly beneficial because of their ability to swell and form a gel that additionally improves the control of drug release and bioavailability [47].

Table 6: Applications of Mucilage-Based Floating Systems with Example Drugs

10. Comparative Analysis: Natural vs Synthetic Polymers in FDDS.

Polymers are key to the design of floating drug delivery systems (FDDS), which affects the ability to remain afloat, release drugs, and ensure stability of the system. Historically, HPMC, carbopol, and polyethylene oxide are synthetic polymers that were commonly utilized. Nevertheless, interest has switched towards natural mucilage because it is safe, sustainable, and multifunctional.

10.1 Advantages of Natural Mucilage

10.1.1 Biocompatibility

Natural mucilage has been shown to be very biocompatible and non-toxic, thereby suitable in pharmaceutical use. Mucilage is produced by plants and is generally well-tolerated by biological systems and does not form harmful degradation products.

• Lessens toxicity and risk of irritation.
• Long-term safe.
• Appropriate in paediatric and geriatric formulations.

Moreover, natural polymers can be considered safe, making it easier to be accepted by the regulatory authorities than synthetic excipients [48].

10.1.2 Cost-Effectiveness

Natural mucilage can be found in great abundance in renewable vegetation sources and can be harvested by relatively simple and inexpensive methods.

• Reduced cost of production as compared to synthetic polymers.
• Ready availability of raw materials.
• Less reliance on complicated chemical synthesis.

This renders mucilage especially appealing to large-scale industrial manufacturing and developing nations, where cost factors are of great concern [49].

10.2 The limitation Natural Mucilage are as follows:

10.2.1 Batch-to-Batch Variability

Among the key issues that are linked to natural mucilage are changes in composition and performance due to variations in:

• Plant species
• Harvesting conditions
• Extraction methods
• Geographical origin

Such variability may cause inconsistencies in:

• Swelling behaviour
• Viscosity
• Drug release profile

These variations can impact reproducibility and quality control in pharmaceutical formulations[50].

 10.2.2 Additional Limitations

• Risk of microbial contamination owing to natural sources.
• Reduced mechanical strength in comparison to synthetic polymers.
• Stability problems with different environmental conditions.

Despite such limitations, appropriate approaches of standardization, purification, and modification have the potential to substantially increase the functionality of natural mucilage in FDDS. [51].

Table 7: Comparison Between Natural Mucilage and Synthetic Polymers

11. Latest Developments and Studies in Floating Drug Delivery Systems.

Recently, floating drug delivery system (FDDS) has been developed to improve targeted delivery, release and responsiveness of the systems. Some of the new technologies that have significantly enhanced the functionality of mucilage-based formulations are nanotechnology, hybrid polymer systems and smart floating systems.

11.1 Nanotechnology Integration

Nanotechnology has revolutionized FDDS since it now can be developed to form nano sized carriers such as nanoparticles, nanospheres and nanocomposites. These systems offer:

•      Increased surface area to dissolve drug.

•      High permeability and absorption.

•      Improved drug stability

Natural mucilage into nanocarriers yields biocompatibility and mucoadhesive properties that lead to improved gastric retention and targeted delivery. Nano-enabled floating can also be used to achieve dual purpose, as it can also be used to deliver drugs at a nanoscale with buoyancy [52].

In addition, floating nanocarriers have been shown to be useful in the delivery of poorly soluble drugs with improved bioavailability and requiring less frequent administration [53].

1.2 Hybrid Polymer Systems

The combinations of natural mucilage and the synthetic polymers to eliminate one or the other of the limitations with the aim of achieving a certain degree of synergies are the hybrid polymer systems.

Advantages:

•           Improved mechanical strength

•           Greater stability and reproducibility.

•           Slow absorption and release of drugs.

To demonstrate this, optimum gel strength and sustained release work are achieved using mucilage with polymers, including HPMC or carbopol. These hybrid systems also reduce the variation of the batch of natural polymers, without compromising on its biocompatibility [54].

Hybrid preparations are particularly convenient in achieving tailored drug release characteristics and they are suitable where the therapeutic requirements are complex.

 11.3 Smart Floating Systems

The new generation of FDDS is known as smart floating systems, which responds to environmental signals, e.g. pH, temperature, or ionic strength.

Characteristics:

Stimulus gelation or swelling.

•           Controlled discharge of drugs based on physical parameters.

•           Improved targeting efficiency

They are pH-sensitive hydrogel and thermo-responsive polymers that undergo phase transitions at the gastric environment. The systems have enhanced bioadhesion and release properties, in combination with natural mucilage [55].

A personalized medicine has a high chance of success with Smart FDDS, as they can adapt to the particular physiological conditions and provide customized therapeutic effects

.

Figure 6: Emerging Trends in Mucilage-Based Floating Drug Delivery