Homogeneity and Surface Morphology: –  The homogeneity of gel formulations is usually assessed by visual inspection and the surface morphology by using scanning electron microscopy. Generally, the swollen gel is allowed to freeze in liquid nitrogen and then lyophilized by freeze drying. It is assumed that the morphologies of the swollen samples are retained during this process. The lyophilized hydrogel is gold sputter coated and viewed under an electron microscope.

pH:- Many gelling agents show pH – dependent gelling behavior. They show highest viscosity at their gel point. Determination of pH is therefore important to maintain consistent quality. As conventional pH measurements are difficult and often give erratic results, special pH electrodes are used for viscous gels. Flat surface digital pH electrodes from Crison, combination electrodes that contain a built-in temperature probe, a bridge electrolyte chamber and movable sleeve junction from Mettler, and combination pH puncture electrodes with spear shaped tip from Mettler are some commercially available pH measurement systems for semisolid formulations.

Alcohol Content:- Alcohol levels in some gel preparations are determined by gas chromatographic (GC) methods. Desoxymetasone gel USP and naftifine hydrochloride gel USP contain 18 – 24% and 40 – 45% (w/w) of ethyl alcohol, respectively. In a desoxymetasone gel, the sample is dissolved in methanol and injected into a gas chromatograph for quantitative analysis. Isopropyl alcohol is used as an internal standard. In naftifine hydrochloride gel, n-propyl alcohol is used as an internal standard and water is used as the diluting solvent.

Rheological Studies:- Viscosity measurement is often the quickest, most accurate, reliable method to characterize gels. It gives an idea about the ease with which gels can be processed, handled, or used. Some of the commonly used tests for characterizing rheology of gels are yield stress, critical strain, and creep. Yield stress refers to the stress that must be exceeded to induce flow. This helps in characterizing the flow nature of non – Newtonian systems. Critical strain or gel strength refers to the minimum energy needed to disrupt the gel structure. When samples are subjected to increasing stress, viscosity is maintained as long as the gel structure is maintained. When the gels intermolecular forces are overcome by the oscillation stress, the sample breaks down and the viscosity falls. The higher the critical strain, the better the physical integrity of gel systems. Creep or recovery helps in assessing the strength of bonds in a gel structure. This is assessed by determining relaxation times, zero – shear viscosity, and viscoelastic properties.
Based on the nature of the test material, different techniques are employed to measure the rheological parameters of gels. Very sophisticated automatic equipment is commercially available for measurements. Cup and bob viscometers and cone  and  plate viscometers are widely used for viscous liquids and gels. They measure the frictional force that is created when gels start flowing. These viscometers are usually calibrated with certified viscosity standards before each measurement. General – purpose silicone fluids which are less sensitive to temperature change are used as standards. The viscosity of gels is affected by the experimental temperature and shear rate and the gels exhibit liquid – or solid like properties. Hence the viscosity of these non – Newtonian systems are recorded at several shear rates under controlled temperatures. The USP specifies the operating conditions for each gel formulation. Commercially available viscometers include Brookfield rotational viscometers, Haake rheometers, Schott viscoeasy rotational viscometers, Malvern viscometers, and Ferranti – Shirley cone and  plate viscometers.

Bioadhesion:- This test is performed to assess the force of adhesion of a gel with biological membranes. The bioadhesive property is preferred for ophthalmic, nasal buccal, and gastroretentive gel formulations. Drugs applied as solutions, viscous solutions, and suspensions drain out from these biological locations within a short time and only a limited fraction of drug elicits the pharmacological activity. Products with higher bio adhesion thus help in increasing the contact time between drugs and absorbing surface and improve their availability. The bio adhesive properties of gels are measured using various custom – designed equipment. All the equipment, however, measures the force required to detach the gel from a biological surface under controlled experimental conditions (e.g., temperature, wetting level, contact time, contact force, surface area of tissue). A typical bio adhesion measurement system consists of a moving platform and a static platform. A tissue from a particular biological region is fixed onto these platforms and a known quantity of the test product is uniformly applied to the tissue surface of the lower static platform. The upper moving platform is allowed to contact with the product surface with a known contact force. After allowing for a short contact time, the moving platform is separated from the product with a constant rate. The force required to detach the mucosal surface from the product is recorded. The analog signals generated by precision load cells are then converted to digital signals through data acquisition systems and processed using specific software programs.

Stability Studies:- Being dispersed systems containing water in their matrix, gels are prone to physical, chemical, and microbial stability issues. Syneresis is a commonly observed physical stability problem with gels. It involves squeezing out dispersion medium due to elastic contraction of polymeric gelling agents. This results in shrinkage of gels. Syneresis can be determined by heating the gels to a higher temperature followed by rapid cooling using an ice water bath at room temperature. The sample is preserved at 4 ° C for about a week, and water loss from the gel matrix is measured. Water loss is measured by weighing the mass of the gel matrix after centrifugation. Absence of syneresis indicates higher physical stability of gels. The chemical stability of drugs in the gel matrix is determined using stability – indicating analytical methods. Studies are conducted at accelerated temperature, moisture, and light conditions to determine the possible degradation of drug in the gel.

Ex Vivo Penetration:- Ex vivo studies are carried out to examine the permeation of drug from gels through the skin or any other biological membrane. As with in vitro release studies, ex vivo penetration is conducted using vertical diffusion cells or modified cells with flow – through design. In this case, the receiver side is filled with phosphate buffer solution of pH 7.4 to simulate the biological pH of human blood. Skin samples from different animal sources such as rats, rabbits, pigs, and human cadavers are used for screening dermatological products. The stratum corneum layer of the skin is separated from the dermis before mounting onto the diffusion cells. The epidermis is separated by immersing the skin sample in normal saline or purified water which is maintained at 60°C for 2 min followed by immersion into cold water for 30s. Careful peeling helps in the separation of the epidermis layer from the dermis. This layer is mounted between the donor and receiver sides and studies are conducted after application of test gel over the surface of the stratum corneum in the donor side. Samples are withdrawn at different time intervals and analyzed for drug permeation by suitable analytical techniques.
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