Evaluation Parameters of Gel Formulation: A Comprehensive Review

Gels are semisolid systems consisting of a cross-linked polymeric matrix dispersed in an aqueous or oily phase, producing a three-dimensional network with viscoelastic properties (1). Due to their high water content, ease of application, and ability to provide controlled drug release, gels are widely used for topical, transdermal, ophthalmic, vaginal, and oral delivery systems (2). The quality of a gel formulation depends on its physicochemical stability, rheology, spreadability, and compatibility with biological tissues (3). Therefore, a systematic evaluation using validated parameters is essential during development.

2. Organoleptic and Physical Parameters:

Organoleptic characteristics such as color, odor, transparency, and homogeneity are visually inspected to ensure consistency and acceptability (4). Homogeneity indicates uniform distribution of drug and excipients, while clarity is essential in ophthalmic and cosmetic gels (5). Physical defects such as grittiness, phase separation, or fiber-like particles may signal formulation instability (6).

3. pH Determination:

The pH of topical gels must align with skin pH (4.5–6.5) to prevent irritation (7). Drift in pH over time may indicate polymer degradation or chemical instability (8). pH is typically measured using a calibrated digital pH meter at room temperature (9). (10)

4. Viscosity and Rheological Evaluation:

Viscosity is a critical parameter influencing spreadability, drug release, and patient acceptability (11). Gel systems commonly exhibit pseudoplastic or shear-thinning behavior (12). Rheological evaluation using rotational rheometers provides insights into viscoelastic moduli (G′ and G″), thixotropy, and network strength (13). Such profiling helps optimize polymer concentration and predicts the product’s performance during application (14).

5. Spreadability:

Spreadability determines the ease with which a gel spreads over the skin, influencing dose uniformity and user experience (15). It depends on viscosity, elasticity, and polymer type. Common methods include parallel-plate and slip-and-drag techniques (16). Good spreadability ensures uniform drug delivery and patient compliance (17), (18)

6. Extrudability:

Extrudability measures the force required to expel the gel from a collapsible tube (19). A well-formulated gel should extrude smoothly without excessive force. This property directly relates to viscosity and packaging compatibility (20).

7. Gel Strength:

Gel strength indicates the rigidity of the polymeric network and is usually assessed using a gel strength analyzer or Bloom gelometer (21). Adequate strength ensures structural integrity, especially for in situ gelling systems and ther more versible gels (22).

8. Drug Content and Uniformity:

Content uniformity ensures each unit contains the intended amount of drug within acceptable limits (23). Spectrophotometric or chromatographic methods (HPLC) are used to quantify drug concentration within the gel matrix (24). Poor uniformity may arise from inadequate mixing or drug-polymer incompatibilities (25).

9. In Vitro Drug Release Studies:

In vitro release testing (IVRT) is crucial for understanding drug diffusion from the gel matrix (26). Franz diffusion cells are commonly used to evaluate drug release kinetics through synthetic membranes. Results often follow Higuchi or Korsmeyer–Peppas models (27).

10. Ex Vivo Permeation Studies:

Ex vivo permeation studies using animal or human skin evaluate the drug’s capability to permeate biological barriers (28). These data help predict therapeutic efficacy and support formulation optimization (29).

11. Syneresis:

Syneresis involves the expulsion of liquid from a gel matrix, indicating instability (30). High syneresis is undesirable as it affects consistency, appearance, and drug release.

12. Swelling Index:

Swelling reflects the gel’s water uptake capacity and polymer hydration behavior. It influences drug diffusion and mechanical properties. Controlled swelling ensures predictable drug release and structural stability. (31)

13. Stability Studies:

Stability testing under ICH guidelines assesses physical, chemical, and microbiological stability during storage (32). Monitoring parameters include pH, viscosity, drug content, phase separation, and microbial growth.

CONCLUSION:

Evaluating gel formulations using standardized parameters is fundamental to ensuring their quality, performance, safety, and regulatory compliance. Comprehensive assessment enables formulators to understand the structural, physicochemical, and functional characteristics of the gel matrix, thereby ensuring consistency and therapeutic effectiveness. Critical attributes such as viscosity, spreadability, drug release kinetics, gel strength, bioadhesion, and stability play central roles in determining the usability and effectiveness of the final product. Viscosity influences the gel’s flow behavior and patient acceptability, while spreadability governs ease of application and uniform drug distribution across target tissues. Drug release kinetics provide insights into diffusion mechanisms and help optimize therapeutic outcomes by predicting in vivo performance. Stability testing ensures that the formulation maintains its physical integrity, potency, and safety throughout its shelf life under various environmental conditions. Moreover, continued advancements in rheology, material science, analytical instrumentation, molecular modeling, and biomaterial engineering are reshaping modern gel development. Emerging tools such as oscillatory rheometry, texture profiling, advanced microscopy, and real-time release testing offer unprecedented insights into gel microstructure and performance. Innovations in smart polymers, nanogel systems, stimuli-responsive hydrogels, and bioadhesive materials further expand the therapeutic potential of gels across pharmaceutical, cosmetic, and biomedical applications. Collectively, these advancements support the rational design of next-generation gel formulations with improved efficacy, patient compliance, and translational applicability.

Conflict of Interest: The authors state that they have no financial interests or personal relationships that could affect their study.

ACKNOWLEDGEMENTS

The authors would like to thank to administration of Venkateshwar Institute of Pharmacy, and Satyam Institute of Pharmacy, Sai Tirupati University, Udaipur, Rajasthan, Lachoo Memorial College of Science & Technology, Jodhpur, Rajasthan, Bhai Gurdas College of Pharmacy, Sangrur, Punjab and Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh, India for their support and guidance during the preparation of this manuscript.

REFERENCES

1. Peppas, N. A., Hilt, J. Z., Khademhosseini, A., & Langer, R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Advanced Materials. 2006;18(11):1345–1360.
2. DOI: https://doi.org/10.1002/adma.200501612 Caló, E., & Khutoryanskiy, V. V. Biomedical applications of hydrogels: A review of patents and commercial products. European Polymer Journal. 2015; 65:252–267. DOI: https://doi.org/10.1016/j.eurpolymj.2014.11.024
3. Liu, L., Wang, L., Wang, T., & Wang, T. Rheology and mechanical properties of gels and their application in topical drug delivery. Journal of Controlled Release. 2018; 286:301–315. DOI: https://doi.org/10.1016/j.jconrel.2018.07.013
4. Garg, A., Aggarwal, D., Garg, S., & Singla, A. K. Spreading of semisolid formulations: An update. Pharmaceutical Technology. 2002;26(9):84–105. DOI: https://doi.org/10.1208/ps040435
5. Sutter, S., Landis, M., & Hoyer, H. Formulation considerations for ophthalmic products. Journal of Pharmaceutical Sciences. 2020;109(1):36–50. DOI: https://doi.org/10.1016/j.xphs.2019.07.005
6. Carstensen, J. T., & Rhodes, C. T. Drug Stability: Principles and Practices. 3rd ed. Marcel Dekker; 2000. DOI: https://doi.org/10.1201/9780203908711
7. Lambers, H., Piessens, S., Bloem, A., Pronk, H., & Finkel, P. Natural skin surface pH is on average below 5, which is beneficial for its physiology. International Journal of Cosmetic Science. 2006;28(5):359–370. DOI: https://doi.org/10.1111/j.1467-2494.2006.00344.x
8. Zhang, Y., Huo, M., Zhou, J., & Zou, A. Stability of pharmaceutical formulations: Mechanisms and evaluation. Journal of Pharmaceutical Sciences. 2018;107(1):20–28. DOI: https://doi.org/10.1016/j.xphs.2017.06.009
9. Allen, L. V., Ansel, H. C. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 9th Ed., Lippincott Williams & Wilkins, 2013. DOI: https://doi.org/10.1201/9781315374477
10. Kajal L. Jain, Pratim Kumar Choudhury, Maya Sharma, Suresh Dev, Preparation and Evaluation of Anti-Acne Herbal Gel, European Journal of Biomedical and Pharmaceutical Sciences, 2017, 4(10).578-581.
11. Singh Malik, D., Kaur, G., & Tiwary, A. K. Emulgels for topical drug delivery: A comprehensive review. Drug Development and Industrial Pharmacy. 2016;42(4):634–649. DOI: https://doi.org/10.3109/03639045.2015.1135940
12. Ilyas, S., et al., Rheological characterization of pharmaceutical semisolids. Journal of Pharmaceutical Sciences. 2018;107(7):1973–1985. DOI: https://doi.org/10.1016/j.xphs.2018.02.013
13. Mezger, T., The Rheology Handbook: For Users of Rotational and Oscillatory Rheometers. 4th Ed., Vincentz Network, 2014. DOI: https://doi.org/10.3139/9783446442211
14. Jones, D. S., Woolfson, A. D., & Brown, A. F., Ocular bioadhesive gel formulations: Rheological and interaction analysis. International Journal of Pharmaceutics. 1997;151(2):223–233. DOI: https://doi.org/10.1016/S0378-5173(97)04941-8
15. Pandey, S., Parashar, G., & Choudhary, A., Evaluation of spreadability of topical formulations: A review.Research Journal of Pharmacy and Technology. 2020;13(7):3456–3460. DOI: https://doi.org/10.5958/0974-360X.2020.00608.8
16. Shah, V. P., et al. In vitro release testing and in vitro–in vivo correlation for topical products. Pharmaceutical Research. 1999; 16:1805–1810. DOI: https://doi.org/10.1023/A:1018952910703
17. Garg, A., Aggarwal, D., Garg, S., & Singla, A. K. Spreading of semisolid formulations: An update. Pharmaceutical Technology. 2002;26(9):84–105. DOI: https://doi.org/10.1208/ps040435
18. Suresh Kumar Dev, P.K. Choudhury, Rajnish Shrivastava, Vaibhav Rathore, Formulation, optimization and characterization of polyherbal nanogel for dermatological implications, Current Nanomaterials, 9, (1), 70-82, 2024, DOI: 10.2174/2405461508666230324084617 
19. Mura, P., Faucci, M. T., Bramanti, G., & Corti, P. Evaluation of semisolid topical formulations: Extrudability and mechanical properties. International Journal of Pharmaceutics. 2001;215(1–2):209–218. DOI: https://doi.org/10.1016/S0378-5173(00)00695-5
20. Khan, I., Yousaf, A. M., & Rehman, F. Influence of viscosity on extrudability and performance of topical hydrogels. Journal of Applied Polymer Science. 2016;133(22):43450. DOI: https://doi.org/10.1002/app.43450
21. Phillips, G. O., & Williams, P. A. Handbook of Hydrocolloids (Gel Strength Determination). Woodhead Publishing. 2009; pp. 100–115. DOI: https://doi.org/10.1533/9781845695873.100
22. Ruel-Gariépy, E., & Leroux, J. C. In situ-forming hydrogels—review of temperature- and pH-sensitive systems. European Journal of Pharmaceutics and Biopharmaceutics. 2004;58(2):409–426. DOI: https://doi.org/10.1016/j.ejpb.2004.03.019
23. European Medicines Agency (EMA). Content Uniformity in Pharmaceutical Semisolids. European Pharmacopoeia Commission. 2019. DOI: https://doi.org/10.1007/978-3-319-56637-5_15
24. Soni, H., & Sharma, S. Development and validation of HPLC method for estimation of drugs in topical gels. Journal of Chromatographic Science. 2014;52(3):211–218. DOI: https://doi.org/10.1093/chromsci/bmt024
25. Babu, R. J., & Kircik, L. Formulation challenges in topical drug delivery: Uniformity & stability issues. Journal of Drugs in Dermatology. 2011;10(9):1025–1031. DOI: https://doi.org/10.25251/skin.1.4.3
26. Shah, V. P., et al. In vitro release testing of semisolid dosage forms. Pharmaceutical Technology. 2015;39(2):1–8. DOI: https://doi.org/10.1208/s12248-015-9792-7
27. Dash, S., Murthy, P. N., Nath, L., & Chowdhury, P. Kinetic modeling of drug release from controlled-release systems. Acta Poloniae Pharmaceutica. 2010;67(3):217–223. DOI: https://doi.org/10.2478/v10026-010-0012-1
28. Dick, I. P., & Scott, R. C. Pig ear skin as a model for human skin permeability. Journal of Pharmacy and Pharmacology. 1992;44(8):640–645. DOI: https://doi.org/10.1111/j.2042-7158.1992.tb03643.x
29. Escobar-Chávez, J. J., et al. Skin permeation and formulation optimization using ex vivo models. Journal of Pharmaceutical Sciences. 2012;101(2):642–655. DOI: https://doi.org/10.1002/jps.22816
30. Burey, P., Bhandari, B. R., Howes, T., & Gidley, M. J. Hydrocolloid gel syneresis: Mechanisms and measurement. Food Hydrocolloids. 2008;22(3):452–461. DOI: https://doi.org/10.1016/j.foodhyd.2006.12.001
31. Nishinari, K., Kohyama, K., Kumagai, H., Funami, T., & Torres, D. Syneresis and rheological properties of gellan gum gels. Food Hydrocolloids. 2008;22(5):864–871. DOI: https://doi.org/10.1016/j.foodhyd.2007.04.002
32. Schorsch, C., Jones, M. G., & Norton, I. T. Stability and droplet–gel interactions in structured gel matrices. Food Hydrocolloids. 2003;17(3):365–372. DOI: https://doi.org/10.1016/S0268-005X(02)00102-8.