Pharmaceutical Gels and Recent Trends –A Review


Suchithra. A. B, S. Jeganath*, E. Jeevitha

Department of Pharmaceutics, School of Pharmaceutical Sciences, Vels Institute of Science, Technology and Advanced Studies (VISTAS), Pallavaram, Chennai - 600117, India

*Corresponding Author E-mail:



The main intention of writing this review was to include the recent literature and specially focusing area of development in topical preparation and basic concept of topical drug delivery systems. Topical drug delivery has advantages such as applying the drug directly into skin and it also provides prolonged action on the specific site. There are different topical used formulation among the semisolid dosage forms gel formulations are becoming pre-eminent. Gels are colloids that are 99% liquid by mass, which is immobilized by surface tension among it and a macromolecules system of fibres constructed from a less amount of gelatinous substances present. The nature of solvent used categorizes gel into mainly two basic types ie, organogel and hydrogel. This review includes fundamental advantages of gel formulation above other semisolid formulation and also other aspects like limitation, classification, formulation, mechanism involved and factors affecting gel formulation.


KEYWORDS: Skin, Pharmaceutical gels, Characteristics, Classification, Preparation, Evaluation of gels.




Topical drug administration is through skin which is a localized drug delivery system all over in the body such as ophthalmic, vaginal, rectal1. Skin is one among the most promptly open organ on human beings for topical administration2.



Skin has been described as the mirror of body and it is the prime organ of the body. Skin is also a hindrance between the body’s internal and external environment3.



Fig.1. Structure of skin

Anatomy and physiology of skin:

Skin covers the body and continuous with the membranes lining the body orifice4. Skin is the largest organ. Skin varies thickness of an average being 1-2mm but it is 6mm on palms and soles and 0.5m on eye lide5.


Layers of skin


Fig.2. Layers of skin


There are two major layers of skin4


Dermis or Corneum:




Epidermis is mainly shallow layer of skin is comprised of stratified epithelium. Epidermis is approximately 0.4-1.5mm in thickness it is the cellular external layer of skin, which is made up of 5 layers4,3.

·       Stratum corneum

·       Stratum lucidum

·       Stratum granulosum

·       Stratum spinosum

·       Stratum germinativum


·       Stratum corneum:

It is the outer most layer also called as hony layer3 which provides mechanical protection to skin. It acts as a wall against loss of water. It is composed of coenocytes. These cells lack nuclei due to pressure and become dead cells. Cells contain a protein known as keratin A that prevent from water evaporation6,7.

·       Stratum lucidum:

This consist flattened epithelial cells3. The cells exhibit shiny character. This is mostly found on palm and soles. The layer resemble lustrous zone so it is called stratum lucidum.

·       Stratum granulosum:

This is made up of granular cells which are thin layer 2-5 rows of compressed rhomboid cells8. Keratohyalin granules are present in cytoplasm. It prevents water loss and mainly seen in palm and soles.

·       Stratum Spinosum:

This is also called prickle cell layer for the reason that containing spinous cells which have spine-like appearance3. They are also compound of keratin filaments4.

·       Stratum germinativum:

It contain polygonal cells externally and column or cuboidal epithelial cells in more profound parts. It contains mitotically active keratocytes and also glands and keratin structures are derived from this layers9,10



Dermis is interior coating of skin. Which is tough and elastic; dermis composes collagen fibres interlaced with elastic fibers4. The collagen fibres, show flexible property and are fit for holding water an enzyme collagenase which is liable for wound healing is present in collagen fibers3. There are mast cells and fibroblast in the dermis4. Dermis comprises of 2 layers11,12.

·       Superficial papillary layer

·       Deeper reticular layer


·       Superficial papillary layer 

This layer projects to epidermis pigment-containing cells. Which is called chromatophores are present in this layer and it also consists of nerve fibres, blood vessels and lymphatics13.

·       Deeper reticular layer

This is comprised of elastic and reticular fibres. This fibres present nearby the sebaceous gland, sweat glands and hair bulbs. Glands are present in the dermal layer of skin14,15.


Sweat glands

Sebaceous glands


Routes of drug permeation through skin:

Three foremost routes of skin absorption16,17

1) Primary, Transcellular: The chemical moieties are transported all the way through keratin packed coenocytes into and out of cell membrane.

2)   Secondary, Intercellular: The molecules are transported around coenocytes in the lipid-rich extracellular region.

3) Thirdly, Transappendageal: This transports are been supported by sweat glands, hair follicles and sebaceous glands.



Gels are semisolid preparation proposed for use on the skin or the mucous membrane2. This is a semi-rigid structure in which the movement of dispersing medium in dispersed phase is limited by an interweaving three-dimensional system of particles18,19. Vast quantity of watery or hydroalcoholic fluid are entangled in a system of colloidal solid particles which may comprise of organic polymers from synthetic or natural origin or Inorganic substances2.


Fig.3. Gel


Structure of gels:

The gelling agent which forms network by interlinking particles result in the rigidity of gel20,21. Type of force which causes the linkage of particles and its nature govern the arrangement of system and gel properties1,22. The single particles show isometric aggregates or spherical cluster of minute molecules or solo macromolecules. The arrangement of gel networks are shown in [Fig.4].



Fig.4: Gel structures. (a) Flocculated particles. (b) Network of stretched out particles or rods. (c) Matted fibres as found in soap gels. (d) Amorphous and Crystalline zones in a gel.


Gel-forming substances:

Gel structural network is formed using polymers. Polymers which forms gel are categorized as follows 23.


Natural Polymer:

A   Proteins: Collagen, Gelatin.

B   Polysaccharides: Agar, Alginic acid, Guar gum, Xanthin, Pectin, Tragacanth.


Semisynthetic polymers:

A   Cellulose derivatives

B   Methyl cellulose


Synthetic polymers:

A   Carbomer

B   Polyethylene and its co-polymer


Surface active agents:

A   Cetostearyl alcohol

B   Brj - 96


Inorganic substance:

A   Bentonite

B   Aluminium hydroxide


Advantages of gel formulations:

Some main advantages of gel formulation over other semisolid dosage forms17, 20

1)   Gels are effortless to prepare when compared to other formulations.

2)   Gel is elegant non-greasy formulation.

3)   Gels have excellent adherence property to application site.

4)   Gels are biocompatible andeco-friendly.

5)   Have magnificent tolerability to stress conditions.


Disadvantages of gel formulation:

In spite of several advantages. Gel formulations also have some disadvantages, 2, 6

1)   Effect of gels is relatively sustained and slower.

2)   The gelators or additives may cause irritation.

3) Water content increases possibility of fungal or microbial attack in gel.

4)   Solvent loss from the formulation dries of gel.

5)   Flocculation in some gel causes an unstable gel.


Classification of gels:

Gels are grouped dependent on the physical nature, solvent’s nature in colloidal phases and rheological properties.1


Based on colloidal phases:

They are categorized into,

·       Two-phase system (Inorganic)

·       Single phase system (Organic)

·       Two-phase system (Inorganic)


If particle size of dispersed phase is comparatively big causes three-dimensional structures all over gel, this framework comprise of floccules of little particles than bigger atoms, the gel structure in this framework isn't steady dependably. They become liquids on agitation and thixotropic forming semisolids on standing24, 25.


Single phase system (Organic):

Big organic molecules are been dissolved in a continuous phase. Continuous phase be made up of big organic molecules on the twisted strands diffuse in it. They use to entrap with one another or bound with each other by Vander walls forces or random motion26.


Based on nature of solvent:

·       Water-based (Hydrogels)

·       With a non - aqueous solvent (Organogels)

·       Xerogels

·       Water-based (Hydrogels)

·       Water has been their continuous liquid phase. Eg - gelatin, carpooler, cellulose derivatives.

·       With a non - aqueous solvent (Organogels)


These have non-fluid solvents as their continuous phase. Eg- olag (aerosol) gel, metallic stearate dispersion in oils, polyethylenes with low molecular weight dissolved in mineral oil and short cooled.



Xerogels are low solvent containing solid gels. There are made by freeze-drying or vaporization of solvent. Eg- Dry cellulose, Polystyrene, Tragacanth ribbons27.


Based on rheological properties

Gels show non-Newtonian flow properties:

They can be categorized as,

·       Plastic gels.

·       Pseudoplastic gels.


·       Plastic gels:

Aluminium hydroxide flocculated suspension show a plastic flow and plot of rheogram provides the yield value of gels beyond which the elastic gel changes and initiates to flow. Eg: Bingham bodies28.


·       Pseudoplastic gels:

Here thickness of gels reduces with rising rate of shear. As the shearing stress is raises the irregularly arranges molecular start to align their lengthy axis in the way of flow releasing solvent from gel matrix. Eg: sodium alginate, Na CMC29.


Based on physical nature:

·       Elastic gels

·       Rigid gels


·       Elastic gels:

Gels of alginates, agar, guar gum and pectin showan elastic action. The fibrous particles are associated at the point of intersection by comparatively weak bonds such as dipole attraction and hydrogen bonds. Eg: Carbopol and aligned 30.


·       Rigid gels:

This are found in macromolecular in which the frame work associated by primary valance bond. Eg: Silica acid molecules aligned by Si-O-Si-O- bond to produce a polymer structure owning a network of pores in silica gel31.


Gel preparation:

Gels are industrial scale preparation usually below room temperature. Following methods can be used for preparation of gels.1,5

1) Thermal changes

2) Flocculation

3) Chemical reaction


1)Thermal changes:

Lipophilic colloids when they are exposed to thermal alterations result in gelatin. If temperature decreases the amount of hydration also decreases and gelation occurs. Eg: Agar, gelatin, and cellulose derivative32. etc.


2) Flocculation:

Gelation is produced by pouring adequate amount of salt to precipitate to make age state but inadequate to bring whole precipitation it is essential to make sure quick mixing to overcome local high concentration of precipitation. The gel formed by flocculation method are thixotropic in behaviour. Eg: Solution of ethyl cellulose 33.


3) Chemical reaction:

Chemical interaction between the solvent and solute result in gel formation Eg: Formulation of Aluminum hydroxide gel.


Mechanism of gel formation:

Gels are formed via three types of cross-linking,6,7

a) Chemical cross-linking

b) Physical cross-linking

c) Ionic cross-linking





(a)                                             (b)                                     (c)

Fig. 6: Various forms of cross-linking

(a)    Chemical cross-linking (b) Physical cross-linking
(c) Ionic cross-linking


a) Chemical cross-linking:

Chemical cross-linkage is found also with polymer possessing bonded group in their assembly. When cross-linkage compounds are bringing together such polymers cause an irreversible reaction among the added compound and free group. After attaining a specific concentration viscosity increases in this type of reaction and results in gel formation34. Eg: Polyacrylic acid (with multiple carboxylic acid) 


b) Physical cross-linking:

By hydrogen bond formation solution to gel transition can be obtain also in cases like concentration variation, temperature variation transition, crystalline component solubilization.  physical cross-linking is shown in Eg: Cellulose gels, Dextran gels 34


c) Ionic cross-linking:

Here cross-connecting occur by making charge on polymer(S) or different particles (Solvent) that attract one another resulting in gel. Charges on the molecules result in Ionic bonds formation. Eg: Polysaccharide alginate produce gel matrix in company of calcium ions result in gel matrix of calcium ions result in gel matrix that encapsulates some compounds35 (enzymes).


Manufacturing of gels:

Normally water soluble excipients are firstly dissolving in vehicle, by using mechanical stirrer in an agitating vessel. To avoid aggregation a hydrophilic polymer is incorporated gradually to the agitated mix. Till dissolution of polymer occurs stirring is continued. If excessive stirred result in air entrapment. The mixing rate must be constant or mixing vessel used must pull out vacuum to prevent from air entrapment.1, 9

Evaluation parameters of gel:

a) Measurement of PH

b) Drug content

c) Viscosity study

d) Spreadability

e) Extrudability study

f) Skin irritation study

g) In-vitro dissolution studies

h) In-vivo dissolution studies

i) Stability

j) Homogeneity

k) Grittiness


a) Measurement of pH1, 10

PH can be determined by using digital PH meter.

Eg- 1g of gel mixed in 100 ml distilled water and stored for 2 hrs. Measurement of PH in triplicate and average value is calculated.


b) Drug content:

1 g of gel dissolved with 100 ml of appropriate solvent stoke solution has been filled. The prepared aliquots of different concentration by using suitable dilution and absorbance are measured. Linear regression analysis of calibration curve is used to calculate the drug content.


c) Viscosity study:

Brookfield viscometer is used for its study rotate the gels at 0.3, 0.6 and 1.5 Rpm. Resultant dial reading are been noted at each speed. Viscosity was obtained by dial reading X factor set in the brook field viscometer catalogues.


d) Spreadability:

It show the coverage of region to which gel easily spreads on application to the affected part or skin. The curative efficacy is depended on spreading value. The time in sec taken by two slides to fall off from gel which is kept in between the slides towards the path of certain lead is expressed or spreadability less time taken better spreadability36. It can be designed with the formula


Spreadability [s] = M x L/T



M= Weight tied to upper slide

L= Length of glass slides

T= Time taken to detached the slides.


e) Extrudability studies:

Before setting inside the container formulations are packed in the collapsible tubes. This is found out in terms of mass in gm. Necessary to extrude a 0.5cm ribbon at gel in 10 second37.


f) Skin irritation study:

For this study, guinea pigs (400-500 g both sex) were used. Which are kept on normal animal food and free contact to water. Hair was shaved from back 5ml of every sample was removed periodically at 1,2,3,4,5,6,7 and 8 hr and every sample is interchanged by equivalent size of new dissolution medium. Then drug content of sample analyzed by using PH buffer guinea pigs and zone of 4cm noted as blank on each side’s one side as test and other side as control. The gel applied twice a day for one wear and place was detected for any sensitive reactions.


g) In-Vitro diffusion studies:

It is done by using Franz diffusion cell, for learning dissolution discharge of gel done by a cellophane membrane. 0.5 of gel sample occupied in cellophane membrane. Diffusion studies done at 37±1oC using PH buffer (PH 7.4) 250ml as dissolution medium.


h) In-vivo studies:

It is done in 6 male Wistar albino rats divided into 3 groups. Rubbing 100mg of prepared gel carefully twice at 1 and 2h on each paw. Calculate the percentage of inhibition by using mercury plethysmometer.


i) Stability:

It is done by freeze-thaw cycling. The products are kept under temperature of 4oc for 1 month again 25oc for 1 month and next at 40oc for 1 month, and syneresis have being detected. The gels are kept a troom temperature and find the liquefied exudates separately.


Application for gels:

·       Used in soft and hard gel pills.

·       Preparation of suppositories Eg- glycerin in suppositories bp.

·       Gels are used to create continuous release formulation.

·       Used for drug administration to various routes such as, tropical, intranasal, intraocular, vaginal, rectal and intramuscular and parenteral in some cases.

·       They are widely used in food and cosmetic industry.

·      Phosphoric acid and Sodium fluoride gel used in dental care2,37.




Gels are getting popularity now a day. Due to their stability and they can offer controlled release comparing to other semisolid preparation like, ointments, creams, pastes etc. The making of gels can show enhanced absorption and hence can enhance the bioavailability of the therapeutic drug. This stability characteristics of gels over an prolonged duration offer scope for its beneficial use for patients. Gels are easy to prepare but it needs significant optimization among the drug and excipient for the production of stable, efficient, and safe product. The basic advantages of topical drug delivery is directing the drug’s therapeutic activity to the specific spot of condition by permitting increase of elevated local concentration of drug with in the tissue around its vicinity to enhance action of drug this can be more effective when the drug have narrow therapeutic window, short biological half-life and are applied topically. The clinical evidence show that gels are safe and efficient way of treatment for diseases.



1.      Hemendrasinh J Rathod and Dhruti P Mehta. “A Review on Pharmaceutical Gel”. Acta Scientific a International Journal of Pharmaceutical Science, International Journal of Pharmaceutical Sciences 1.1 (2015): 33-47.1)

2.      Syeda Ayesha Ahmed un Nabi, Muhammad Ali Sheraz*, Sofia Ahmed, Nafeesa Mustaan, Iqbal Ahmad, Pharmaceutical Gels: A Review, RADS-JPPS Vol 4 (1), June 2016, 40-4.

3.      Prateek Chittodiya*, Rajesh Singh Tomar*, Umesh Ramchandani, Dr. Nimita Manocha, Dr. Shikha Agrawal, Topical Gel - A Review, International Journal of Pharmaceutical & Biological Archives 2013; 4(4): 606 – 613.

4.      Text book of cosmetics, Rajesh Kumar Nema, Kamal Singh Rathore, Bal Krishna Dubey, CBS Publishers & Distributors. (First edition 2009, reprint – 2015) page no – 29 to 34. 

5.      Basha B. Niyaz, Prakasam Kalyani, Goli Divakar. Formulation and Evaluation of Gel containing Fluconazole-Antifungal Agent. International Journal of Drug Development & Research 2011; Vol. 3(4): 109-128.

6.      Labarre D, Ponchel G, Vauthier C. Biomedical and Pharmaceutical Polymers. Pharmaceutical Press, London, UK, 2010.

7.      Gad SC. Pharmaceutical Manufacturing Handbook: Production and Processes. Wiley-Blackwell, Hoboken, USA, 2008.

8.      Vollmer B. Polymer Chemistry. Springer Science & Business Media, New York, USA, 2011.

9.      Jones D. “Pharmaceutics-Dosage Form and Design”. 1st ed. London: Pharmaceutical Press (2008).

10.   Goyal S, Sharma P, Ramchandani U, Shrivastava S.K., Dubey P.K “Novel Anti-Inflammatory Topical Herbal Gels Containing With an iasomnifera and Boswelliaserrata”. International Journal of Pharmaceutical and Biological Archives 2.4 (2011): 1087.

11.   Khurram Rehman and Mohd Hanif Zulfakar, Review article, Recent advances in gel technologies for topical and transdermal drug delivery, Published online 13 August 2013.

12.   Ramanji Saini, Seema Saini, Gurpreet Singh, Dr. Angshu Banerjee, International Journal of Pharma Sciences and Research (IJPSR), In situ gel a new trend in ophthalmic drug delivery system,2015.

13.   Sebastián L. Vega1, Mi Y. Kwon, and Jason A. Burdick, Recent advance in hydrogels for cartilage tissue engineering, Department of Bioengineering, Author manuscript in PMC 2018 January 01, 33: 59–75.

14.   Arti Vashist1, Ajeet Kaushik, Atul Vashist, Rahul Dev Jayant, Asahi Tomitaka1, Sharif Ahmad, Y. K. Gupta, and Madhavan Nair, Recent trends on hydrogels based drug delivery systems for infectious diseases, Biomater Sci. 2016 October 18; 4(11): 1535–1553.

15.   Pavithra K, Jeganath S*, azeemiqbal (2018) 'Design, development, and characterization of topical gel containing itraconazole - antifungal agent', Asian journal of pharmaceutical and clinical research, 11(4), pp. 153-158.

16.   Yang K, Han Q1, Chen B1, Zheng Y1, Zhang K1, Li Q1, Wang J1, Antimicrobial hydrogels: promising materials for medical application [pubmed].

17.   LoydVA, Nicholas G. Popovich, Howard C. Ansel. “Ansel’s pharmaceutical dosage forms and drug delivery systems. 9th ed. Philadelphia: Lippincott Williams & Williams; (2011).

18. [Internet]. Gel [updated 2014 December 13]. Available from:

19.   Jain N.K. Pharmaceuticals Product Development. CBS Publishers & Distributors Pvt. Ltd. 2006; First edition: 228-230. 

20.   Florence AT, Attwood D. Physicochemical Principles of Pharmacy. Pharmaceutical Press, London, UK, 2011.

21.   Cooper and Gunn. “Disperse systems. In: Carter SJ, editor. Tutorial Pharmacy”. CBS Publishers and Distributors (2000): 68-72.

22.   Bharadwaj Sudhir, Gupta G.D, Sharma V.K. Topical Gel: A Novel approach for drug delivery. Journal of Chemical Biological and Physical Sciences 2012; Vol. 2(2): 856-866.

23.   Sebulingam K, Sembulingam Prema. Essentials of Medical Physiology. Jaypee Brothers Medical Publishers (P) Ltd. New Delhi 2000; Second edition: 256-257.

24.   Attwood D.  “Disperse systems. In: Aulton ME, editor. Pharmaceutics-The Science of Dosage Form Design”. London: Churchill Livingstone (2002): 83-85 85-91, 528-529.

25.   Ranade VV and Hollinger MA. “Transdermal drug delivery. In: Kydonieus AF, Berner B, editors. Transdermal delivery of drugs”. Volume I. Boca Raton: CRC Press (2004): 207-248.

26.   Kydonieus AF. “Fundamentals of transdermal drug delivery. In: Kydonieus AF, Berner B, editors. Transdermal delivery of drugs”. Volume I. Boca Raton: CRC Press (1987): 3-16.

27.   Allen L. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Lippincott Williams & Wilkins, Philadelphia, 2014.

28.   Felton L. Remington: Essentials of Pharmaceutics. Pharmaceutical Press, London, UK, 2013.

29.   Nittur J. R. kunchu k. Theetha G. and Tamizh M. Review on In situ Ophthalmic Gels: A Developing Trend, Int. J. Pharma. Sci. Rev. & Res., 2011, 7(1):08-14.

30.   Rathore K.S. In situ Gelling Ophthalmic Drug Delivery System: An Overview, Int.  J. Pharm. Pharm. Sci., 2011, 2(4):30¬34.

31.   Waugh Anne, Grant Allision. Ross and Wilson Anatomy and Physiology in health and illness. Churchill Livingstone Elsevier 2006; Tenth edition: 360-362.

32.   Prakash Shashi, Nair Anroop, Saini Vipin, Sahu Neelam. Skin Kinetics and Dermal Clearance. International Research Journal of Pharmacy 2012; Vol. 3(8): 14-15.

33. s/chapter02.htm

34.   Bhowmik Debjit, Gopinath Harish, Kumar B. Pragati, Duraivel S, Kumar KP Sampath. Recent Advances in Topical Drug Delivery System. The Pharma. Innovation Journal 2012; Vol. 1(9): 12.

35.   Jr. Loyd V. Allen, Popovich Nicholas G, Ansel Howard C. Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Lippincott Williams & Wilkins 2005; Eighth edition: 276. 

36.   Singla Vikas, Saini Seema, Joshi Baibhav and Rana A.C. Emulgel: A new Platform for Topical Drug Delivery. International Journal of Pharma and Bio Sciences 2012; Vol. 3(1): 486,490.

37.   Reddy G. Sarath Chandra, Anil Reddy Dr. B, Pranitha Chodavaraple Naga, Suryadevera Haritha. Organogel - A Review. International Journal of Pharmacy & Technology 2010; Vol. 2(4): 584-585.






Received on 30.04.2019           Modified on 29.06.2019

Accepted on 30.07.2019         © RJPT All right reserved

Research J. Pharm. And Tech. 2019; 12(12): 6181-6186.

DOI: 10.5958/0974-360X.2019.01073.4