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1. Gels Gels are semisolid preparations that contain small inorganic or l arge organic molecules interpenetrated by a liquid Gels are attractive delivery systems they are simple to manufacture suitable for administering drugs through skin, oral, buccal , ophthalmic, nasal, otic, and vaginal routes They also provide intimate contact between the drug and the site of action or absorption

2. TYPES OF GELS Gels may be classified into two primary types: Hydrogels , which have an aqueous continuous phase, and Organogels , which have an organic solvent as the liquid continuous medium Gels may also be classified based on the nature of the bonds involved in the three-dimensional solid network Chemical gels and , form when strong covalent bonds hold the network together Physical gels form when hydrogen bonds and electrostatic and van der Waals interactions maintain the gel network

3. may also be classified as, Two-phase systems (magma) consists of floccules of small distinct particles The gel structure in the two-phase systems is not always stable thus may thicken on standing, forming a thixotropic, and must be shaken before use to liquefy the gel and enable pouring E.g., Milk of magnesia comprises a gelatinous precipitate of magnesium hydroxide Single-phase systems are gels in which the macromolecules are uniformly distributed throughout a liquid with no apparent boundaries between the dispersed macromolecules and the liquid  

4. Characteristics Gels may appear transparent or turbid based on the type of gelling agent used. They exhibit different physical properties, namely, imbibition , swelling, syneresis , and thixotropy . Imbibition refers to the uptake of water or other liquids by gels without any considerable increase in its volume . Swelling refers to the increase in the volume of gel by uptake of water or other liquids . This property of most gels is influenced by temperature, pH, presence of electrolytes, and other formulation ingredients Thixot ropy refers to the non -Newtonian flow nature of gels, which is characterized by a reversible gel to sol formation with no change in volume or temperature

5. Syneresis refers to the contraction or shrinkage of gels as a result of squeezing out of dispersion medium from the gel matrix It is due to the excessive stretching of macromolecules and expansion of elastic forces during swelling On cooling, the osmotic pressure of the system decreases therefore the expanded elastic forces return to normal This results in shrinkage of the stretched molecules and squeezing of dispersion medium from the gel matrix Addition of osmotic agents such as sucrose, glucose, and electrolytes helps in retaining higher osmotic pressure even at lower temperatures and avoids syneresis of gels.

6. Gelling Agents A large number of gelling agents are commercially available for the preparation of pharmaceutical gels In general, these materials are high - molecular - weight compounds obtained from either natural sources or synthetic pathways They are water dispersible , possess swelling properties , and improve the viscosity of dispersions

7. An ideal gelling agent should not interact with other formulation components should be free from microbial attack Changes in the temperature and pH during preparation and preservation should not alter its rheological properties. It should be economic readily available form colorless gels provide cooling sensation on the site of application, and possess a pleasant odor.

8. Cellulose derivatives The cellulose derivatives represent a family of chemically related polysaccharides that are structurally derived from cellulose The most commonly used examples from this series that are used to formulate pharmaceutical gels include methylcellulose hydroxyethylcellulose hydroxypropylcellulose sodium carboxymethylcellulose

9. Polysaccharides derived from natural sources Polysaccharides that have been derived from natural sources are commonly used as the basis for pharmaceutical gels E.g., (1) alginic acid/sodium alginate & (2) carrageenan ; Alginic acid/sodium alginate is a polysaccharide that is derived from algae It is used in gels due to its thickening and swelling properties insoluble in water but, it absorbs 200 – 300 times its own weight of water and swells Addition of calcium salts increases viscosity of alginic acid gels. Its viscosity decreases at higher temperature Depolymerization due to microbial attack also results in viscosity reduction Alginic acid is incompatible with basic drug molecules

10. Carrageenan is derived from red seaweed There are three chemically related carrageenans , termed lambda, iota and kappa which differ according to the location of sulphate groups and the presence or absence of anhydrogalactose κ - carrageenan exhibits excellent gelling properties (due to the presence of a tertiary helical structure ); ι - Carrageenan also displays gelling (albeit weaker) properties Carrageenan is soluble in hot water and forms gels at 0.3 – 2.0%.

11. Carbomer Carbomers are one of the widely used gelling agents in topical preparations due to their extensive swelling properties obtained by cross - linking acrylic acid with allyl sucrose or allyl pentaerythritol . Various grades with varying degree of cross - linking and molecular weight are commercially available It is acidic b/c about 60% carboxylic acid present in its composition Carbomer 934P, 971P, 974P, 940 and so on, are used for preparing clear gels. Aqueous dispersions of carbomers are usually low viscous, and on neutralization they form high - viscous gels b/c the pendant carboxyl groups will ionize , resulting in expansion of the polymer chains due to repulsion of the adjacent ionised groups

12. Preparation Gels are relatively easier to prepare compare to ointments and creams In addition to the gelling agent, medicated gels contain drug, antimicrobial preservatives, stabilizers, dispersing agents, and permeation enhancers Some of the factors are essential to obtain a uniform gel preparation Order of m ixing Gelling m edium Processing conditions and duration of swelling Removal of e ntrapped a ir

13. Order of Mixing The order of mixing of ingredients with the gelling agent is based on their influence on the gelling process If they are likely to influence the rate and extent of swelling of the gelling agent, they are mixed after the formation of gel In the absence of such interference, the drug and other additives are mixed prior to the swelling process. In this case, the effects of mixing temperature, swelling duration, and other processing conditions on the physicochemical stability of the drug and additives are also considered Ideally the drug and other additives are dissolved in the swelling solvent, and the swelling agent is added to this solution and allowed to swell.

14. Gelling Medium Purified water is the most widely used dispersion medium in the preparation of gels. Under certain circumstances, gels may also contain cosolvents or dispersing agents. A mixture of ethanol and toluene improves the dispersion of ethylcellulose , Dichloromethane and methanol increase the viscosity of hydroxypropyl cellulose dispersions, Alcohol improves the rheological stability of polyethylene oxide gels Inclusion of glycerin, propylene glycol, sucrose, and alcohol improves the dispersion of sodium alginate dispersions.

15. Processing Conditions and Duration of Swelling The processing temperature , pH of the dispersion, and duration of swelling are critical parameters in the preparation of gels. These conditions vary with each gelling agent. For instance, hot water is preferred for gelatin and polyvinyl alcohol , and cold water is preferred for methylcellulose dispersions. Carbomers, hydroxypropyl cellulose, poloxamer, & tragacanth form gels at weakly acidic or near - neutral pH conditions (pH 5 – 8) C arboxymethyl cellulose sodium, hydroxypropylmethyl cellulose, and sodium alginate form gels over a wide pH range (4 – 10). Hydroxyethyl cellulose forms gel at alkaline pH condition. A swelling duration of about 24 – 48 h generally helps in obtaining homogeneous gels. Natural gums need about 24 h cellulose polymers require about 48 h for complete hydration.

16. Removal of Entrapped Air Entrapment of air bubbles in the gel matrix is a common issue, especially when the swelling process involves a mixing procedure or the drug and other additives are added after the swelling process . Positioning the propeller at the bottom of the mixing container minimizes to a larger extent Further, can be achieved by long term standing , low temperature storage, sonication , or inclusion of silicon antifoaming agents. In large - scale production, vacuum vessel deaerators are used to remove the entrapped air.

17. Packaging and storage Being viscous and non - Newtonian systems, gels need high attention during packing into containers. Usually they are packed into squeeze tubes or jars made of plastic materials Aluminum containers are also used when the product pH is slightly acidic As most of the gels contain an aqueous phase, preservation in airtight containers helps in protecting them from microbial attack Usually they are preserved at room temperature and protected from direct sunlight and moisture.

18. Creams Pharmaceutical creams are semisolid preparations containing one or more medicinal agents dissolved or dispersed in either a water-in-oil (W/O) emulsion or an oil-in water (O/W) emulsion Hydrophilic creams (Oil-in-Water creams) contain large amounts of water in their external phase and stearic acid or other oleaginous components.. Example: Vanishing cream After application of the cream, the water evaporates, leaving behind a thin residue film of the stearic acid or other oleaginous component are more comfortable and cosmetically acceptable as they are less greasy and more easily washed off using water

19. Hydrophobic creams (Water-in-Oil creams) contain water in the internal phase. Example: Cold cream. W/O creams are more difficult to handle but many drugs which are incorporated into creams are hydrophobic and will be released more readily from a water-in-oil cream than an oil-in-water cream W/O are also more moisturizing as they provide an oily barrier which reduces water loss from the stratum corneum Creams are softer than ointments and are preferred because of their easy removal from containers and good spreadability over the absorption site

20. Preparation The solid excipients are melted at the time of preparation emulsifiers are used to disperse the hydrophilic components in the hydrophobic dispersion phase (e.g., water - in - oil creams) or oleaginous materials in aqueous dispersion medium (oil - in - water creams) Preparation usually involves separating the formula components into two portions: lipid and aqueous. The lipid portion contains all water-insoluble components and the aqueous portion the water-soluble components.

21. Both phases are heated to a temperature above the melting point of the highest melting component The phases then are mixed, and the mixture is stirred until reaching ambient temperature or the mixture has congealed Mixing is continued during the cooling process to promote uniformity. Traditionally, the aqueous phase is added to the lipid phase, but comparable results have been obtained with the reverse procedure The active pharmaceutical ingredients (APIs) can be added to the phase in which it is soluble at the beginning of the process, or it can be added after the cream is prepared by a suitable dispersion process such as levigation or milling with a roller mill.