INTRODUCTION:

The creation of controlled and long-lasting drug delivery systems has received more attention over the past 30 years. Polymeric drug delivery methods have been the subject of substantial investigation. In situ gel systems have gotten a lot of interest in recent years. A growing variety of in situ gel forming technologies have been researched in recent years, and many patents for their use in diverse biological applications, including drug administration, have been published. By virtue of its unique 'Sol to Gel' transition, the in-situ gelling technology aids in the continuous and regulated release of medications, increased patient compliance, and comfort. An in-situ gelling system is a formulation that, before it enters the body, is in solution form but transforms into a gel under specific physiological conditions. Temperature, pH change, solvent exchange, UV radiation, and the presence of certain molecules or ions all influence the sol to gel transition.

In situ gel formulations provide an intriguing option to establishing systemic drug effects via parenteral routes, which can be inconvenient, or oral routes, which can result in unacceptably poor bioavailability and pass-through hepatic first-pass metabolism, especially for proteins and peptides. Different natural and synthetic polymers are gelled in situ and can be used for oral, ocular, transdermal, buccal, intraperitoneal, parenteral, injectable, rectal, and vaginal administration. Recent developments in in situ gels have made it possible to take advantage of changes in physiological properties in various GI tract sections for enhanced drug absorption as well as patient convenience and compliance. Pectin, gellan gum, chitosan, alginic acid, guar gum, Carbopol, xyloglucan, xanthan gum, HPMC, poloxamer, and other natural polymers are used in in situ gelling systems. This article focuses on an overview of in situ gels and the many polymers that can be employed in them^1-3.

Advantages^4,5:

· It helps for patient compliance and comfort by making medicine administration easier.

· It also minimises the frequency of administration.

· It aids in the prolonged or extended release of medicines.

· It reduces both local and systemic toxicity.

· Natural polymers contain inherent biocompatibility, biodegradability, and biodegradability qualities. Supporting cellular activity using physiologically identifiable molecules.

· Synthetic polymers have well-defined structures that can be tweaked to achieve acceptable degradability and usefulness.

Disadvantages^6,7:

· It involves a large number of fluids.

· The drug's sol form is more sensitive to deterioration.

· Only medications with a minimal dose requirement may be administered.

· There is a risk of instability due to chemical breakdown.

· Eating and drinking may be restricted for a period of time after the medication is implanted.

CLASSIFICATION OF IN SITU GEL POLYMERS:

In situ gelling systems are classified into two types:

· Natural polymers: Sodium alginate, pectin, chitosan, Gellan gum, xanthan gum, Carbopol, sodium hyaluronate etc.

· Synthetic or semi-synthetic polymers: polyacrylic acid, Cellulose acetate phthalate, poloxamer, hydroxypropyl methylcelluloseetc.

Natural polymers:

· Sodium alginate:

Alginic acid is a polysaccharide made up of 1, 4-glycosidic linkages between β-D-mannuronic acid and α-L-glucuronic acid residues. Depending on the algal source, the percentage of each block and the order in which blocks are arranged along the molecule varies. By a cooperative process involving sequential glucuronic residues in the α-L-glucuronic acid blocks of the alginate chain, dilute aqueous solutions of alginates produce solid gels when di and trivalent metal ions are added. Alginic acid can be employed as a carrier for ocular formulations due to its favourable biological properties, such as biodegradability and nontoxicity. Alginic acid formulations were studied for a prolonged precorneal stay due to its mucoadhesive properties as well as its ability to gel in the eye^8,9.

· Pectin:

Pectin is a polysaccharide that consists primarily of α-β-(1-4)-D galacturonic acid residues. In the egg-box model, free calcium ions crosslink galacturonic acid chains to quickly form gels in aqueous solution when low methoxy pectin (degree of esterification 50%) is present. Pectin gels in the presence of H+ ions, hence the creation of gels that can be employed as drug delivery systems requires a source of divalent ions, usually calcium ions. Because pectin is water soluble, it can be employed in these formulations without using organic solvents. When pectin is taken orally, divalent cations in the stomach help it transition from a liquid to a gel state^10.

· Chitosan:

Chitosan is a thermosensitive, biodegradable polycationic polymer made from the alkaline deacetylation of chitin, a natural component of shrimp and crab shells. Chitosan is a biocompatible cationic polymer that dissolves in aqueous solutions and has a pH of 6. When a chitosan aqueous solution is neutralised to a pH greater than 6.2, a hydrated gel-like precipitate form. Chitosan aqueous solutions of pH-gelling cationic polysaccharides are converted into thermally sensitive pH-dependent gel-forming aqueous solutions without any chemical modification or cross-linking by adding polyol salts with a single anionic head, such as glycerol, sorbitol, fructose, or glucose phosphate salts^11,12.

· Gellan gum:

Sphingomonas elodea secretes gellan gum, an anionic hetero polymer. It is made up of glucose, rhamnose, and glucuronic acid, which are all joined together to form a tetra saccharide unit. Gelrite is deacetylated gellan gum that has had the acetyl group removed by alkali treatment. Gelrite gels as a result of instillation in the residence of calcium ions. In the food business, gellan gum is employed as a suspending and stabilising agent, with the production of double helical junction zones followed by aggregation of double helical segments to form three-dimensional networks via complexing with cations and hydrogen bonding with water^13.

· Xanthan gum:

High molecular weight extracellular polysaccharide xanthan gum is produced by the gram-negative bacterium Xanthomonas campestris. This naturally occurring cellulose derivative has a cellulosic backbone (β-D-glucose residues) and a trisaccharide side chain of β-D-mannoseβ-D-glucuronic acid α-D-mannose connected to the main chain's alternate glucose residues. This polymer has an anionic property because the side chain contains both glucuronic acid and pyruvic acid groups.

· Carbopol:

Carbopol is a well-known pH-dependent polymer that remains in solution at acidic pH but gels at alkaline pH with a low viscosity. HPMC is utilised in conjunction with Carbopol to increase the viscosity of the Carbopol solution while lowering the acidity. pH-induced in-situ precipitating polymeric systems include a variety of water-soluble polymers such as the Carbopol system-hydroxypropyl methylcellulose system and poly (methacrylic acid)-poly (ethylene glycol). The creation and assessment of an ocular administration system for indomethacin for the treatment of uveitis was carried out based on this notion. In vitro, a sustained release of indomethacin was detected for 8 hours, making this method an attractive option for ocular administration^14.

· Sodium hyaluronate:

It's the sodium salt of hyaluronic acid in a water-soluble form. It is a natural, endogenous carbohydrate that aids in the body's collagen production and flexibility maintenance. It also improves the stability of the formulation and minimises the risk of oxidation^15,16.

Synthetic or Semi- synthetic polymers:

· Cellulose acetate phthalate:

Pseudo latex is another name for CAP. Its synthetic latex made by dispersing a pre-existing polymer in an aqueous media. Due to the fact that latex is a free-running solution with a pH of 4.4 and that tear fluid, which undergoes coagulation, raises the pH to pH 7.4, it is a pH sensitive, cross-linked polyacrylic polymer with potential advantages for sustained drug administration to the eye. CAP, which does not require for the use of organic solvents, is used to determine the ocular residence time of an ophthalmic solution in γ -scintigraphy^17.

· Hydroxypropyl methyl cellulose:

The glucan chain in cellulose is made up of repeated β-(1, 4)-D-glucopyranose units. Temperature sensitive sol-gel phase transition is observed in some natural polymers such as HPMC, MC, and EC. When the temperature drops, cellulose material increases its viscosity, while its derivatives, such as HPMC and MC, increase their viscosity when the temperature rises. MC is a naturally occurring polymer formed of native cellulose chains that have an additional methyl substitution group. When the temperature is low (300C), the solution is liquid, but as the temperature rises (40-500C), it gels^18.

· Polyacrylic acid:

Carbopol is the brand name for PAA. In ophthalmology, it's commonly utilised to improve pre-corneal retention. When compared to other cellulose derivatives, it has outstanding mucoadhesive characteristics^19.

· Poloxamer:

Pluronic is a brand name for poloxamers, which are utilised in thermosensitive in situ gels. It has good thermal setting qualities and extends the duration that drugs stay in the body. It's a water-soluble tri-block copolymer made up of two polyethylene oxide (PEO) and polypropylene oxide (PPO) molecules (PPO). Because of its colourless and transparent gel-forming properties, Pluronic F127 is the most widely utilised poloxamer polymer in pharmaceuticals. It is made up of 70% PEO and 30% PPO (30 %). Pluronic F127-g-poly (acrylic acid) was employed as an in-situ gelling carrier to extend the residence period and improve ocular medication absorption^20,21.

CONCLUSION:

For in-situ gel formulation, biocompatible, biodegradable, and water-soluble polymers can provide great and outstanding drug delivery systems. Researchers have shown an increased interest in sophisticated drug delivery strategies in recent years, giving them a lot of room to grow. These methods can be integrated into a unique carrier to achieve significantly enhanced and extreme medication delivery. Finally, gels in situ are simple to use and provide patient comfort and compliance.

ACKNOWLEDGEMENT:

I am highly thankful to the management of Yashoda Technical Campus Satara for their support and encouragement.

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Received on 19.11.2022 Modified on 27.07.2023

Asian J. Res. Pharm. Sci. 2024; 14(1):77-80.

DOI: 10.52711/2231-5659.2024.00012