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Department of Pharmaceutics Shree Dev Bhoomi Institute of science and technology Pondha Rd, Mahajun, Uttarakhanda 248007
The most popular method of administering drugs is through an oral route of administration. Many parts are crucial in the formulation of the drug delivery system. Polymers are among the elements of macromolecules that have changed along with the drug delivery mechanism, polymers are chains of monomers. Based on their origin, the two main types of polymers are employed in drug delivery systems that are synthetic and natural. Each variety of polymers possesses certain benefits and drawbacks. This article lists a number of natural polymers, including sodium alginate, guar gum, chitosan, xanthan gum, and Gellan gum. The most often used synthetic polymers are ethylcellulose, HPMC, eudragit, and carbapol. For those drugs that are mostly absorbed in the upper parts of the gastrointestinal (GI) tract, the gastro retentative drug delivery system (GRDDS) or floating drug delivery system (FDDS) become an extra benefit. Due to their lower density than stomach content, floating drug delivery systems have emerged as an important and cutting-edge technique during the past few decades. The goal of preparing this review article is to concentrate on the uses of synthetic and natural polymers floating drugs delivery system.
Drug delivery system refers to the delivery of required amount of pure crude form of the drugs either in solid, liquid or semi-solid form, which should be therapeutically efficient, safe and stable, to the specified site in the body to reach instantly, to achieve the correct concentration and then retain the adapted concentration. Oral drug delivery is mostly preferred due to several advantages—including lower treatment costs, higher patient compliance, and convenience of administration—but the frequency of dose is high due to easier stomach emptying of dosage form. (1) Drugs with low solubility and low stability in intestinal fluids can be administered via floating drug delivery system (FDDS), which was developed to retain the dosage form in the stomach. To make the dosage form float at the top of the gastric fluids, FDDS works by making the dosage form less dense than the fluids in the stomach. With enough buoyancy to float over the contents of the stomach and stay buoyant there for an extended amount of time without slowing down the rate of gastric emptying, FDDS are hydrodynamically regulated low density systems. (2) Gastro retention provides better accessibility to novel products with novel therapeutic potential and significant patient benefits. The mechanisms of mucoadhesion, flotation, sedimentation, expansion, changed shape systems, or the concurrent administration of pharmacological drugs that delay stomach emptying can all be used to produce controlled gastric retention of solid dosage forms. (3)
METHODOLOGY
The following keywords were carefully examined in a number of studies published in various journals in order to generate a review article on the use of polymeric exepients utilized for the manufacturing of FDDS: gastric retention, gasretention, and gasretentive systems; floating, floating dosage forms; floating, floating drug delivery system; floating, floating drug delivery; floating tablets; floating beads; floating microspheres; floating capsules; floating systems; buoyant dosage form; gastric-floating drug delivery systems; and gastric floating. A description of the purpose of the polymeric excipients in the pharmaceutical composition, or an indication of how the properties of the dosage form depend on their presence or amount, and the acquisition of an FDDS (or a delivery system with flotation as one of the mechanisms of gastroretention) were the criteria used to include reference articles in the review.
Gastroretentative drugs delivery system (GRDDS)
By extending the gastric residence period, gastro retentive drug delivery aims to target site-specific drugs release in the upper gastrointestinal tract (GIT) for either local or systemic effects. More advantages of this extended retention ability include: extending the duration of action for drugs with short half-lives; increasing the bioavailability of drugs; eliminating side effects; decreasing the frequency of dosage; preserving medications for prior benefits; enhancing the solubility of drugs that are less soluble in high pH environments; optimizing therapy; and, in the end, facilitating patient compliance. Many methods for delivering gastroretentive drugs have been developed over the past few decades. These methods include: high density (sinking) systems that stay in the stomach's bottom; low density (floating) systems that cause dosage form to float in gastric fluid; mucoadhesive systems that cause bioadhesion to the stomach mucosa; unfoldable, extendible, or swellable systems that restrict the amount of dosage forms that can be emptied from the stomach's pyloric sphincter; super porous hydrogel systems, magnetic systems, etc. (4, 5)
Floating drugs delivery system
Low-density systems with enough buoyancy to float above the contents of the stomach and stay buoyant there for an extended amount of time without slowing down the process of gastric emptying are known as floating systems, or FDDS, or hydrodynamically controlled systems. As a result, the fluctuation in plasma concentrations of drugs is better controlled and the stomach retention period is extended. The design of floating tablets is based on the structure modification or gas producing phenomena. (6) By combining the right components with excipients such as hydrocolloids, inert fatty materials, and buoyancy-enhancing compounds, floating dosage forms such as tablets and capsules can be made. FDDS is used in the formulation of several medicine classes: including antacids, antidiabetic, antifungal, and anticancer medications. Compared to gastric fluids, FDDS have a lower bulk density which is buoyant enough to float over the contents of the stomach and stay there for a extended period of time. (7)
Advantages of Floating Drug Delivery System: (8)
Disadvantages of floating drug delivery system (9)
Types of floating Drug delivery system (10)
Non-effervescent systems:
Effervescent systems:
Approaches to design floating dosage form (10)
Single-Unit dosage forms:
Three spherical shells that are apparently less dense than stomach fluid can be employed as drug carriers in low density techniques to allow to regulated release of the drugs from dosage form. Another method for obtaining a buoyant dosage form is to use a system that is filled with fluid and floats in the stomach. Popcorn, pop rice, and polystyrol have all been used as medication transporters in coated shells. These shells have been undercoated with sugar polymeric materials such as cellulose acetate phthalate and methacrylic polymer. A mixture of drugs and polymers is applied on top of these. Depending on the desired kind of release, hydroxypropyl cellulose or ethyl cellulose can be the preferred polymer. Ultimately, the product releases the drugs gradually over an extended period of time while floating on the gastric juice.
Multiple-Unit dosage forms:
The goal of creating a multiple-unit dosage form is to create a dependable formulation that possesses all of the benefits of a single-unit dosage form while also being free of all of the drawbacks of single unit dosage form. Many different unit floatable dosage forms have been devised in an attempt to accomplish this goal. Microspheres possess a substantial loading capacity, and numerous polymers, including albumin, gelatin, starch, polymethacrylate, polyacrylamine, and poly alkyl cyanoacrylate, have been employed. It is possible to create spherical polymeric microsponges, commonly known as "microballoons." Microspheres are characterized by a good in vitro floatability and a characteristic internal hollow structure. There have been various floating dosage form described that contain features that expand, unfold, or get inflated by the carbon dioxide generated in the devices following administration in multiple-unit oral formulations. If the extended diameter of these dose forms exceeds around 12 to 18 mm, they are not allowed to pass through the pyloric sphincter.
Application of floating drug delivery system (7)
The applications of floating drug delivery are
Exepients used in floating drug delivery system (5, 7)
During formulation of floating dosage for these are the mainly used Exepients in the dosage form
Polymers
Polymers are often employed to improve solubility or target drug delivery qualities, polymers are lengthy repeating chains of macromolecules. In order to prevent precipitation within a specific amount of time, polymers function as a precipitation inhibitor by keeping the supersaturated phase through interactions with drugs. Drugs that released from the dosage form dissolve in a supersaturated condition are readily absorbed. (11) Polymers are primarily divided into two categories: synthetic and natural. Natural polymers are preferable because they are non-toxic, more readily available, less expensive, and biodegradable. Conversely, synthetic polymers are used because they have good flow characteristics, can control drug release and stability, determine the drug carrier properties, and enhance drug solubility to boost bioavailability. (12)
On the basis of origin polymers are classified as
Natural polymers
Hydrocolloids made of natural polymers are frequently employed to regulate the release of drugs from swellable systems. Natural polymers are advantageous in the areas of safety, biological, and pharmacological compatibility.
Advantages of natural polymers (13)
Disadvantages of natural polymers (13)
Synthetic polymers
Synthetic polymers are naturally occurring polymers that are processed and purposely shaped for use as polymers.
Advantages of synthetic polymers (13)
Disadvantages of synthetic polymers (13)
Chitosan (14, 15)
The natural polymer obtained from the deacetylation of chitin is chitosan. Its beneficial biological qualities include nontoxicity, biodegradability, and biocompatibility. Because of its antibacterial qualities and bioadhesive nature, this polymer may be delivered to specific sites. With a pka value of 6.2–7, chitosan is a high molecular weight polycationic weak base. On addition to acidic pH of 1.2 or neutral media it become buoyant in nature and provide control release. The rate of release of chitosan film can be reduced by increasing its thickness. It is applied to microspheres at a concentration of 0.5–8%.
Advantages of chitosan:
Xanthan gum (14, 15)
Xanthan gum is an extracellular polysaccharide with a high molecular weight that is obtained through the pure culture aerobic fermentation of carbohydrates. Long chained polysaccharide xanthan gum has a lot of side chains that are trisaccharides. Additionally, gum is resistant to common enzymes and exhibits high solubility and stability in both acidic and alkaline environments, as well as in the presence of salts.
Advantages of Xanthan gum:
Sodium alginate (20)
Sodium alginate consists chiefly of the sodium salt of alginic acid, which is a mixture of polyuronic acids composed of residues of d’mannuronic acid and L guluronic acid. The block structure and molecular weight of sodium alginate Samples have been investigated.
Typical Properties:
Acidity/alkalinity pH-7.2 (1% w/v aqueous solution).
Solubility:
Practically insoluble in ethanol (95%), ether, chloroform, and ethanol/water mixtures in which the ethanol content is greater than 30%. Also, practically insoluble in other organic Solvents and aqueous acidic solutions in which the pH is less than 3. Slowly soluble in water, forming a viscous colloidal Solution.
Viscosity (dynamic):
Various grades of sodium alginate are commercially available that yield aqueous solutions of varying viscosity. Typically, a 1% w/v aqueous solution, at 208C, will have a viscosity of 20–400mpa s (20–400cp). Viscosity may vary depending upon concentration, pH, temperature, or the Presence of metal ions. Above pH 10, viscosity decreases.
Guar gum (23)
Functional Category:
Suspending agent, binder, disintegrant, viscosity increasing agent
Description:
Occurs as an odorless or nearly odorless, white to yellowish-white powder with a bland taste.
Typical Properties
Acidity/alkalinity:
pH = 5.0–7.0 (1% w/v aqueous dispersion)
Density:
1.492 g/cm3
Solubility Practically insoluble in organic solvents, in cold or hot water, guar gum disperses and swells almost immediately to form a highly viscous, thixotropic sol. The optimum rate of hydration occurs at pH 7.5–9.0. Finely milled powders swell more rapidly and are more difficult to disperse. Two to four hours in water at room temperature are required to develop maximum viscosity.
Viscosity:
Viscosity is dependent upon temperature, time, concentration, pH, rate of agitation, and particle size of the guar gum powder. Synergistic rheological effects may occur with other suspending agents such as xanthan gum. It shows dynamic viscosity as 4.86 Pas (4860 cP) for a 1% w/v dispersion
Advantages of guar gum in floating drug delivery system:
It has been reported that polymer swelling play an important role in the pattern and amount of drug release. It was found that guar gum formulations were relatively insensitive to stirring speed during in vitro drug dissolution testing and dissolution profile was not affected significantly
Hydroxypropyl methyl cellulose (HPMC) (25, 26, 27)
Hydroxypropyl methylcellulose ethers belong to an extensive family of white to off-white, odorless, water soluble polymers that bind, retain water, thicken, form films, lubricate. It is a semi synthetic, inert, viscoelastic polymer, used as an excipient and controlled-delivery component in oral medicaments, found in a variety of commercial products.
Functional category:
Bioadhesive material, coating agent, controlled-release agent, dispersing agent, dissolution enhancer, emulsifying agent, emulsion stabilizer, extended-release agent, film-forming agent, foaming agent, granulation aid, modified release agent, mucoadhesive, release modifying agent, solubilizing agent, stabilizing agent, suspending agent, sustained release agent, tablet binder, thickening agent, viscosity-increasing agent . Individual type of HPMC grades exhibits these properties to varying degrees and may have additional properties that are desirable for specific applications.
Apparent density:
0.25~0.70g/cm3
Refractive index:
1.336
Surface tension:
42 to 56mn/m
Solubility:
Soluble in cold water, forming a viscous colloidal solution; practically insoluble in hot water, chloroform, ethanol (95%), and ether, but soluble in mixtures of ethanol and dichloromethane, mixtures of methanol and dichloromethane, and mixtures of water and alcohol. Certain grades of HPMC are soluble in aqueous acetone solutions, mixtures of dichloromethane and propan-2-ol, and other organic solvents. Some are swellable in ethanol.
Advantages
Eudragit (30)
Functional category:
Film former; tablet binder; tablet diluent
Description:
Ethyl cellulose (33)
Functional Category:
Coating agent, flavoring agent, binder, filler, viscosity increasing agent.
Description:
Ethyl cellulose is a tasteless, free-flowing, and white to light tan-colored powder. Typical Properties
Density (bulk) 0.4 g/cm3
Glass transition temperature 129–133°C
Moisture content:
Ethyl cellulose absorbs very little water from humid air or during immersion, and that small amount evaporates readily.
Specific gravity:
1.12–1.15 g/cm3
Solubility:
Ethyl cellulose is practically insoluble in glycerin, propylene glycol, and water. Ethyl cellulose that contains less than 46.5% of ethoxyl groups is freely soluble in chloroform, methyl acetate, and tetrahydrofuran, and in mixtures of aromatic hydrocarbons with ethanol (95%). Ethylcellulose that contains not less than 46.5% of ethoxyl groups is freely soluble in chloroform, ethanol (95%), ethyl acetate, methanol, and toluene
Viscosity:
The viscosity of ethylcellulose is measured typically at 258°C using 5% w/v ethylcellulose dissolved in a solvent blend of 80% toluene: 20% ethanol (w/w). Grades of ethylcellulose with various viscosities are commercially available. They may be used to produce 5% w/v solutions in organic solvent blends with viscosities nominally ranging from 7 to 100 mPas (7–100 cP). Specific ethylcellulose grades, or blends of different grades, may be used to obtain solutions of a desired viscosity. Solutions of higher viscosity tend to be composed of longer polymer chains and produce strong and durable films. The viscosity of an ethylcellulose solution increases with an increase in ethylcellulose concentration; e.g. the viscosity of a 5% w/v solution of Ethocel Standard 4 Premium is 4 mPas (4 cP) and of a 25% w/v solution of the same ethylcellulose grade is 850 mPas (850 cP).
Carbopol (36)
Synonyms:
Arypol, Acritamer, acrylic acid polymer, carbomera, Carbopol, carboxy polymethylene, carboxyvinyl polymer, Pemulen, polyacrylic acid, Tego Carbomer.
Functional Category:
Bioadhesive material; emulsifying agent; emulsion stabilizing agent; modified-release agent; suspending agent; viscosity-increasing agent.
Description:
Carbomers are white-colored, ‘fluffy’, acidic, hygroscopic powders with a characteristic slight odor. A granular carbomer is also available (Carbopol 71G). Carbomer are formed from repeating units of acrylic acid. The polymer chains are crosslinked with allyl sucrose or allyl pentaerythritol
Applications in Pharmaceutical Formulation or Technology
Carbomers are used in liquid or semisolid pharmaceutical and cosmetic formulations as rheology modifiers and emulsifying agents in the preparation of oil-in-water emulsions for external preparations such as creams, gels, lotions and ointments for use in ophthalmic, rectal, topical and vagina preparations. In tablet formulations, carbomers are used as controlled-release agents either alone or in combination with other polymers such as hypromellose and polyvinyl acetate phthalate. In contrast to linear polymers, higher viscosity does not result in slower drug release with carbomers. Lightly cross linked carbomers (lower viscosity) are generally more efficient in controlling drug release than highly crosslinked carbomers (higher viscosity). Carbomers are also used as binders in wet granulation using water, organic solvents, or their mixtures as the granulating fluid. Carbomer polymers have also been studied in the preparation of multiparticulate systems for oral delivery and in oral mucoadhesive controlled drug delivery systems. Caebomer are used in the concentration as Emulsifying agent (0.1-0.5%) Gelling agent (0.5-2%) Suspending agent (0.5-1%) Tablet binder (0.75-3%) Controlled-release agent (5-30%)
CONCLUSION:
The FDDS become an additional advantage for drugs that are absorbed primarily in the upper segments of GI tract, i.e., the stomach, duodenum and jejunum. Polymers are used for the purpose of the controlled release of drug from dosage form. Polymers are the substances which are being used in the formulations for many reasons like gelling agents, emulsifying agents, viscosity increasing agents, rate retarding agents etc. EC, HPMC, Carbopol and Eudragit are most widely and commonly used polymers. There are various expensive polymers also which are synthetic in nature, but chitosan can be the best alternative for this. With proper polymer and surfactant ratio, we can formulate a better floating dosage form having controlled release ability. Synthetic polymers are mostly used in these dosage forms other than natural polymers. Therefore knowledge of the polymer in field of the drug delivery plays an important role. However a lot of work is still needed to be done to overcome the different physiological and pharmaceutical barriers to develop the more effective dosage forms. It is suggested that future research work in the FDDSs should be aimed at discovering means to accurately control the drug input rate into the GI tract for the optimization of the pharmacokinetic and toxicological profiles of medicinal agents.
In spite of various benefit till date, there is very few utilization of this drug delivery system on an industrial level. This delivery system can play a beneficial role in the absorption of acidic active pharmaceutical ingredients with decrease in dosing frequency.
RELEVANT CONFLICT OF INTEREST/FINANCIAL DISCLOSURE:
This author declare that the research was conducted in the absence of any commercial or financial relationship that could be constructed as a potential conflict of interest
REFERENCES
Ram Prasad khoteja? , Aarti Kori , Shivanand Patil, Polymers Used In Floating Drugs Delivery System-A Review, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 8, 3822-3835. https://doi.org/10.5281/zenodo.13371960
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