Polymers Used In Floating Drugs Delivery System-A Review

Abstract

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.

Keywords

Floating Drug Delivery System, Polymers, Natural gums, HPMC, Gastro retentative drug delivery system

Introduction

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)

1. FDDS are beneficial for medications that are absorbed through the proximal part small intestine or stomach. Such as ferrous salts and furosemide.
2. It has been discovered that the effectiveness of medications given using the sustained release concept of floating formulation is unaffected by the location of absorption.
3. The floating drug delivery system is useful for medications intended to work locally in the stomach. For instance, antacids
4. When acidic drugs, such as aspirin, come into contact with the stomach wall, they irritate it. Thus, the administration of aspirin and other such drugs may benefit from the use of HBS formulation.

Disadvantages of floating drug delivery system (9)

1. For those drugs that have problems with stability and solubility in stomach fluid can’t be formulated in FDDS.
2. Drugs with substantial first pass metabolism, such as nifedipine, which is absorbed across the whole gastrointestinal tract can’t be formulated in FDDS.
3. Not suitable for the drugs that are irritant to gastric mucosa.
4. They need an appropriately aberrant level of fluid in the stomach for the dosage form to float in and function properly.
5. These systems also require the presence of food to delay their gastric emptying.
6. A number of factors, including presence of meal, pH, and stomach motility, affect gastric stability.
7. Gastric emptying in prostrate patients may happen at random and turns highly dependent on the breadth and size. Consequently, patients should not be dosed with floating dosage form just before  sleep.

Types of floating Drug delivery system (10)

Non-effervescent systems:

• Hydrodynamic balanced System (HBS) / Single layered floating tablet
• Micro porous compartment Systems / bi- layered floating tablet
• Multi particulate System: Floating Beads / Alginate beads
• Micro balloons / Hollow Microsphere
• Raft forming system

Effervescent systems:

• Volatile liquid containing system
• Gas generating system

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

1. Enhanced bioavailability
2. Sustained drug delivery
3. Site specific drug delivery
4. Reduced fluctuation of drug concentration

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 (synthetic/semi-synthetic/natural)
• Effervescent generating system e.g., sodium bicarbonate, citric acid, tartaric acid, di-sodium glycine carbonate, citroglycine, etc.
• Hydrocolloids e.g., Acacia, pectin, agar, alginates, gelatin, casein, bentonite, veegum, methylcellulose (MC), HPMC, ethylcellulose (EC), HPC, hydroxyethyl cellulose, and carboxy methylcellulose sodium (Na CMC).
• Inert fatty materials e.g., purified grades of beeswax, fatty acids, long chain alcohols, glycerides, and mineral oils.
• Release rate accelerants e.g., lactose, mannitol, etc.
• Release rate retardant e.g., dicalcium phosphate, talc, magnesium stearate, etc.
• Buoyancy increasing agents e.g., polypropylene foam powder, etc.
• •Miscellaneous(fillers/gladiants/lubricants/diluents)

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

1. Natural polymers e.g. chitosan, sod alginate, Xanthan gum, guar gum, carrageen, gelan gum
2. Semi-synthetic polymer e.g. ethyl cellulose, HPMC, eudragit, polyvinyl pyrrolidone
3. Synthetic polymers  are acrylic acid derivative, lactic acid derivatives e.g. Carbopol etc

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)

1. Increased viscosity due to rapid swelling
2. Dissolve in warm and cold water, non-irritating
3. Biodegradable and non-toxic
4. Good compatibility and high stability

Disadvantages of natural polymers (13)

1. Unsuitable to be used for sustained release
2. Incompatible with cationic substance and oxidation substance, sodium carboxyl methylcellulose, dry aluminum hydroxide gel, and several drugs (amitriptyline and tamoxifen)
3. Low stability
4. Very limited single use of carrageenan as GRDDS polymer

Synthetic polymers

Synthetic polymers are naturally occurring polymers that are processed and purposely shaped for use as polymers.

Advantages of synthetic polymers (13)

1. Inert and very soluble, frequently utilized in formulations for prolonged release
2. Varies widely depending on pH
3. Freely Water-soluble

Disadvantages of synthetic polymers (13)

1. Only certain types can float in ethyl alcohol and have limited flow properties
2. Non-biodegradable
3. Difficult to float

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:

• • The film it produces lessens the impact of the gastrointestinal transit time.
  • Hollow microcapsules typically float on stomach juice for twelve hours.
  • The drug's release rate adhered to zero order kinetics.
• Sheth et al. employed the basic emulsification phase separation technique to manufacture and assess chitosan-based floating microspheres utilizing levetiracetam, a BCS class-I drugs with a half-life of 6-7 hours, by altering the proportion of the crosslinking agent i.e. polymer (glutaraldehyde). The formulated microspheres showed more than eight hours of buoyancy and extended drug release. At greater polymer concentrations, the mean particle size increased and the drug release rate dropped. Diffusion-controlled medication release from the microspheres was shown in in-vitro tests (16)
• Sarojini et al. created a floating mucoadhesive microsphere of clarithromycin using a heat stabilization method and span 80, based on albumin-chitosan that can be used to treat stomach ulcers by increasing the antibiotic's contact time, decreasing the diffusional distance, increasing the gastric residence time, and acting locally at the infectious site. Drugs released from microsphere shows first-order release kinetics of the drugs, indicating high-percentage drug release. (17)

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:

• It is used to increase or decrease rate of release of drug from formulation
• Soluble in water
• High viscosity at low concentration
• The drug release at zero order kinetics is a possible benefit. Certain tablets with citric acid and xanthan gum exhibit buoyancy for longer than twenty-four hours.

• Ayesha Naz and Syeda Sadia formulated gastro retentative floating pill by utilizing natural polymers such as carbopol, sodium alginate, and xanthan gum and the drug incorporated was diuretic furosemide. Direct compression technology was used to make the tablets, utilizing a natural polymer to achieve the appropriate drug release. This formulation lengthens the drug's duration in the stomach and releases the medication for a longer amount of time, enhancing the drug's bioavailability.(18)
• Karthi R. formulated and assessed a floating tablet of ciprofloxacin by utilizing natural polymers such as guar gum and xanthan gum. In comparison to floating tablets that just contain a single natural polymer, the tablets made with a combination of xanthan gum and guar gum have demonstrated a longer-lasting impact. .(19)

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.

• Sahasathian Et al. developed mucoadhesive and floating chitosan-coated alginate beads as a gastroretensive delivery vehicle for amoxicillin, toward the effective eradication of Helicobacter pylori, a major causative agent of peptic ulcers. Amoxicillin-loaded alginate beads coated with 0.5% (w/v) chitosan exhibited excellent floating ability, high-encapsulation efficiency, high-drug loading capacity, and a strong in vitro mucoadhesion to the gastric mucosal layer. In vitro, amoxicillin was released faster in simulated gastric fluid than in simulated intestinal fluid. Alginate-chitosan complex could be prepared with a >90% drug encapsulation efficiency and exhibited more than 90% muco-adhesiveness, 100% floating ability, and achieved sustained release of amoxicillin for over 6 h in simulated gastric fluid. (21)
• Murata et al. prepared two types of alginate beads of metronidazole in which one had vegetable oil and second one was with chitosan. The release rate being inversely related to the percentage of oil and was not affected by the kind of chitosan. These release properties of alginate gels are applicable not only for sustained release of drugs but also for targeting the gastric mucosa. (22)

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

• Hajare and Patil designed floating tablet of Metformin Hcl, an anti-diabetic biguanid with poor bioavailability and absorption window at the upper part of gastrointestinal tract prepared by wet granulation method incorporating natural polymers guar gum and k-carrageen and a polymer HPMC either alone or in combination. Formulation prepared with a combination of 6% w/w k-carrageen, and 11%w/w guar gum showed good gel strength, stable, and persistent buoyancy for 12 h, least floating lag time of 58 s with good matrix integrity throughout dissolution period. Comparison study with Glutamet® showed that the optimized formulation has better and complete release than the marketed product. Studies revealed usefulness of natural polymers over synthetic. (24)

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

• Water soluble and most abundant polymer in nature
• Used as a thickener, film former and water retension agent
• Hydrophilic matrix is the simplest sustained release technology for oral dosage form

• Chandira et al. (2010) formulated floating tablets of Itopride hydrochloride, a novel prokinetic drug, were developed to prolong the gastric residence time and thereby increase drug bioavailability. Floating tablets were fabricated; using direct compression method containing Itopride hydrochloride, polymers HPMC K100M, HPMC K15M and carbopol 934 P, along with gas generating agent sodium bicarbonate and citric acid. The results found that tablets containing 125 mg HPMC K100M, 40 mg HPMC K15M, and 40 mg carbopol provided a better option for 24 hours release action and improved bioavailability(28)
• Bomma et al. (2009) prepared floating matrix tablets of norfloxcin which were developed to prolong gastric residence time leading to an increase in drug bioavailability by using wet granulation technique using polymers such as HPMC K4M, HPMC K100M and Xanthan gum. The tablets exhibited controlled and prolonged drug release profile while floating over dissolution medium was confirmed as drug release mechanism from these tablets.(29)

Eudragit (30)

Functional category: 

Film former; tablet binder; tablet diluent

Description:

• Polymethacrylates are synthetic cationic and anionic polymers of dimethylaminoethyl methacrylates, methacrylic acid, and methacrylic acid esters in varying ratios. Several different types are commercially available and may be obtained as the dry powder, as an aqueous dispersion, or as an organic solution. A (60: 40) mixture of acetone and propan-2-ol is most commonly used as the organic solvent. Eudragit S 100 is available as powder and solvents used for this is 95 ?etone and alcohols which is soluble in intestinal fluid from pH 7 and used as an enteric coating material.
• Eudragit L and S also referred to as methacrylic acid copolymers in the USPNF 23 monograph, are anionic copolymerization products of methacrylic acid and methyl methacrylate. The ratio of free carboxyl groups to the ester is approximately 1:1 in Eudragit L (Type A) and approximately 1: 2 in Eudragit S (Type B). Both polymers are readily soluble in neutral to weakly alkaline conditions ( pH 6– 7) and form salts with alkalis, thus affording film coats that are resistant to gastric media but soluble in intestinal fluid. Eudragit L-100 and Eudragit S-100 are white free-flowing powders with at least 95 % of dry polymers.
• Kumar and Rai prepared and evaluated floating microspheres of curcumin for prolonged gastric residence time and increased drug bioavailability by emulsion solvent diffusion method, using HPMC, EC, Eudragit S 100 polymer in varying ratios. Ethanol/dichloromethane blend was used as a solvent in a ratio of 1:1. The floating microspheres showed particle size, buoyancy, drug entrapment efficiency, and yield in the ranges of 251 387 ?m, 74.6 90.6%, and 72.6 83.5%, and 45.5-82.0%, respectively. Maximum drug release after 20 h was 81.3% by the best formulation.(31)
• Wang et al. also developed a multiunit floating dosage form of nitrendipine using EC and eudragit as polymers and compared with the nonfloating polymers having same polymers in which best results are observed in floating dosage forms. When this floating dosage form is compared with conventional dosage form the resultant relative bioavailability was found to be 166.01%. (32)

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).

• Singh et al prepared a floating drug delivery system of famotidine by solvent evaporation technique using EC and HPMC as rate controlling polymer. Results showed that the polymer ratio and stirring speed affected the size, incorporation efficiency, and drug release of microspheres, and the best results were obtained at the ratio of HPMC: EC (1:6). The mean particle size of prepared floating microspheres increased, but the drug release rate from the microspheres decreased as the polymer concentration increased. The developed floating microspheres of famotidine may be used in the clinic for prolonged drug release in the stomach for at least 12 h, thereby improving the bioavailability and patient compliance. (34)
• Vaghani et al. developed a multiple-unit-type oral floating dosage form of 5-fluorouracil to prolong gastric residence time for the treatment of stomach cancer by solvent evaporation method using EC as a polymer. The yields of preparation were very high, and low-entrapment efficiencies were noticed with larger particle size for all the formulations. Mean particle size, entrapment efficiency, and production yield were highly influenced by polymer concentration. Porous EC microspheres are promising controlled release as well as stomach targeted carriers for 5-fluorouracil. (35)

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%)

• • • • Nur and Zhang developed floating tablets of captopril using HPMC (4000 and 15,000 cps) and carbopol 934P. In vitro buoyancy studies revealed that tablets of 2 kg/cm2 hardness after immersion into the floating media floated immediately and tablets with hardness 4 kg/cm2 sank for 3-4 minutes and then came to the surface. Tablets in both cases remained floating for 24 hours. The tablet with 8 kg/cm2 hardness showed no floating capability. It was concluded that the buoyancy of the tablet is governed by both the swelling of the hydrocolloid particles on the tablet surface when it contacts the gastric fluids and the presence of internal voids in the center of the tablet (porosity).  A prolonged release from these floating tablets was observed as compared with the conventional tablets and a 24 hour CR from the DF of captopril was achieved. Admixtures containing Carbopol 940, 941 and NaCMC were assessed for bioadhesive delivery of metronidazole. The bioadhesive properties of the admixtures were estimated by using the adhesion of polymer coated glass beads on a biological tissue and the modified Lecomte Du Nouy tensiometer. The rheological behaviors of the polymers and their admixtures were studied as well. The bioadhesive, swelling and release characteristics of tablet compacts formulated with the polymers and their admixtures, which contained metronidazole, were also determined. Results obtained indicated that although all single polymers and their admixtures had high bioadhesive potentials, Carbopol 940 and 941 admixtures (2:1) showed the best performance and NaCMC/Carbopol 940 admixture (2:1) exhibited the least bioadhesive strength. (37)
      • Vishal G. Karkhile and his co-worker performed study on floating table of furosemide in 2010. They prepare floating tablet of furosemide by direct compression technique to increase solubility of furosemide in water. The effect of concentration of polymer, types of polymer and mixtures of polymer were studied with a view to optimize the formulation of Furosemide. PEG - 6000 is used as carrier agent for increasing solubility of furosemide in water. HPMC, Sodium Bicarbonate and Carbopol were used as matrix forming agent, gas generating agent and floating agent respectively. The optimized floating tablet showed drug release in a controlled manner with higher dissolution for 12hours in comparison with conventional marketed tablet. (38)
      • Prajapati ST, Patel LD, Patel DM. had developed a floating matrix tablet of Domperidone that prolong gastro residence time and thereby increase drug bioavailabilty. Domperidone was choosen as a model drug because it is poorly absorbed from the lower GIT. The tablets were prepared by wet granulation technique using polymer such as HPMC K4M, Carbopol 934P, Sodium alginate, either alone or in combination and other standard excipients. Tablets were evaluated for different parameters. (39)

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

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