Enhanced Topical Therapeutics: A Review on Development and Evaluation of Innovative Emulgel Formulations

Pathan Junaid Moinuddin²*, Mujahid Ahmed Haroon Rasheed²,                               Mr. Faizan Ahmed¹, Obaidurraheman Mohammed Saleem²

1.      Assistant Professor, Dept. of Pharmaceutical Chemistry, Royal College of Pharmaceutical Education and Research, Syne Khurd Malegaon.

2.      B  Pharmacy Royal College of Pharmaceutical Education and Research, Syne Khurd Malegaon.                  

Correspondence: mujahidpharm22@gmail.com;

DOI: https://doi.org/10.71431/IJRPAS.2025.41012

INTRODUCTION

Various routes of administration have been historically employed to treat illnesses, including sublingual, oral, rectal, topical, parenteral, inhalation, etc. For individuals with cutaneous disorders such as acne, eczema, psoriasis, etc., the preferred method is topical delivery, involving the application of the necessary drug to the skin. Although this administration route has a long history, ongoing research and development are focused on exploring and creating advanced methods and technologies to enhance patient compliance.(1) The optimal choice for cutaneous purposes is the topical route of administration, given that the skin, being the most accessible organ, enables the delivery of drugs with superior efficacy compared to other administration routes.(2) Topical preparations are predominantly employed locally to achieve specific effects at the site of application.(3)

It is the best route for the cutaneous purpose. Another name for a localized drug delivery system is a topical drug delivery system. Topical delivery can be applied in various forms, including ophthalmic, nasal, rectal, and vaginal, aiming to minimize side effects and improve bioavailability.(4) Topical products are categorized into two types: external topical and internal topical. External topical products extend to the tissues, covering affected areas of the body. Conversely, internal topical products are administered topically to mucous membranes in the oral cavity, rectal tissues, or vagina to achieve localized effects.(5) Patient adherence, simplicity of application, enhanced drug bioavailability, minimal toxicity, improved physiological and pharmacological responses, particularly beneficial for drugs with a narrow therapeutic window, limited drug exposure to non-infectious organs or tissues, and importantly, it circumvents the first-pass effect – these are some of the advantages of a topical drug delivery system.(6)

   PHYSIOLOGY OF SKIN

Most of the topical preparations are meant to be applied to the skin. So basic knowledge of the skin and its physiology function are very important for designing topical. The skin of an average adult body covers a surface area approximately 2-meter square and receives about one third of the blood circulating through the body. An average human skin surface is known to contain, on the average 40-70 hair follicles and 200-300 sweat ducts on every square centimeter of the skin. The pH of the skin varies from 4 to 5.6. Sweat and fatty acid secreted from sebum influence the pH of the skin surface. The skin can be considered to have four distinct layers of tissue as shown in figure.

·         Non-viable epidermis

Stratum corneum is the outer most layer of skin, which is the actual physical barrier to most substance that comes in contact with the skin. The stratum corneum is 10 to 20 cell layers thick over most of the body. Each cell is a flat, plate like structure 34-44 μm long, 25-36 μm wide,0.5 to 0.20 μm thick with surface area of 750 to 1200 μm stocked up to each other in brick like fashion. Stratum corneum consists of lipid (5-15%) including phospholipids, glycosphingo lipid, cholesterol sulfate and neutral lipid, protein (75-85%) which is mainly keratin.

·         Viable epidermis

This layer of the skin resides between the stratum corneum and the dermis and has a thickness ranging from 50-100μm. The structures of the cells in the viable epidermis are physiochemically similar to other living tissues. Cells are held together by Tono fibrils. The density of this region is not much different than water. The water content is about 90%.

·         Viable Dermis:

Just beneath the viable epidermis is the dermis. It is a structural fibrin and very few cells are like it can be found histological in normal tissue. Dermis thickness ranges from 2000 to 3000 μm and consists of a matrix of loose connective tissue composed of fibrous protein embedded in an amorphous ground substance.

Subcutaneous connective tissue:

The subcutaneous tissue or hypodermis is not actually considered a true part of the structured connective tissue which is composed of loose textured, white, fibrous connective tissue containing blood and lymph vessels, secretary pores of the sweat gland and cutaneous nerves. Most investigators consider drug permeating through the skin enter the circulatory system before reaching the hypodermis, although the fatty tissue could serve as a depot of the drug. Cross section of skin is shown in figure I.

Figure 1: Physiology of skin

Figure 2: Various Dosage Forms Used for Topical Drug Delivery System

EMULGEL

Emulgel is a hybrid pharmaceutical formulation that combines the characteristics of both an emulsion and a gel. It is designed to offer the advantages of both these dosage forms, providing a versatile platform for delivering various active pharmaceutical ingredients (APIs) through topical application. When gels and emulsions are used in combined form the dosage forms are referred as emulgel. (8) Emulgels exist in two variants: either oil in water or water in oil, and their gelation is achieved through the incorporation of a gelling agent. Both varieties of emulgels are extensively employed in the pharmaceutical industry as a carrier for delivering a variety of drugs to the skin. They possess a notable characteristic in that they can readily permeate the skin.(9)

They exhibit characteristics of both gels and emulsions, leading to high patient acceptability. Due to these dual properties, they are commonly employed for delivering diverse drugs to the skin.(10) Emulgels are alternatively referred to as gelled emulsions or creamed gels. Having thixotropic characteristics, emollient properties, easy removal, extended shelf life, environmentally friendly, aesthetically pleasing, transparent appearance, and non-greasy attributes are key advantageous features of emulgels. (11) Emulgels are recognized as an emerging field, although they remain a relatively less marketed product. This aspect renders emulgels a captivating and challenging dosage form to explore. The utilization of emulgels in topical delivery offers numerous advantages. Emulsions consist of two immiscible phases: the dispersed phase and the continuous phase, and the incorporation of an emulsifying agent enhances stability. (12) Emulgels can be either O/W or W/O, with drug particles entrapped in the internal phase. These particles then traverse the external phase and gradually undergo absorption into the skin, imparting a controlled effect. (13)

Topical pharmaceutical formulations such as ointments and creams pose significant drawbacks, including limited spread ability, reduced penetration, and lower patient compliance due to stickiness or the necessity for thorough rubbing during application. Similarly, gels face limitations in delivering hydrophobic drugs. Historically, ointments, creams, and lotions were employed for treating various infections. However, due to various factors and constraints, emulgels have emerged as viable alternatives in both cosmetic and pharmaceutical preparations. (15) The solubility challenge of a drug has been successfully addressed, and the issue of penetration has been effectively resolved as well. Emulgel formulations enable drug globules to permeate soft tissues, leading to a reduction in the required dosage for optimal drug action and an enhancement of pharmacological effects. Moreover, the inclusion of specific excipients further contributes to the pharmacological activity in various ways. Various topical dosage forms, such as moisturizers, creams, and ointments, exhibit several limitations. (16) Some of the challenges include stickiness and greasiness, leading to difficulties in application for patients. These properties can also contribute to stability issues in hydrophilic drug formulations. Due to these drawbacks associated with semi-solid preparations, the adoption of gel formulations has expanded in both pharmaceutical and cosmetic applications. Despite the advantages, a significant challenge remains in delivering hydrophobic drugs effectively. Emulgels offer a solution by combining the benefits of both emulsions and gels. Emulgels enhance drug deposition onto the skin. Nevertheless, topically applied emulgels present several advantages compared to ointments and gels.(17)

ADVANTAGES OF EMULGEL (18)

·      Incorporation of hydrophobic drugs

·      Better loading capacity

·      Better stability

·      Production feasibility and low preparation cost

·      Controlled release

·      No intensive sonication

·      Improve Patient Compliance

DISADVANTAGES OF EMULGEL (18)

·      Skin irritation on contact dermatitis.

·      The possibility of allergenic reactions.

·      The poor permeability of some drug through the skin.

·      Drug of large particle size not easy to absorb through the skin.

·          The occurrence of the bubble during formation of emulgel.

IDEAL PROPERTIES OF DRUG CANDIDATE TO FORMULATE AS EMULGEL

Table 2: Ideal properties of drug candidate to formulate as emulgel(19)

REQUIREMENT OF AN EMULGEL:

Following are the primary requirements of a chemical moiety of an emulgel (Table 1).

Constituents required for preparation of an emulgel:

Oil:

Various oils play a crucial role in the formulation of emulgels. The oil phase commonly incorporates mineral oil, vegetable oil, or fish liver oil. Non-biodegradable minerals and castor oil are extensively utilized in oral preparations, offering a local laxative effect. Additionally, other vegetable oils such as Arachis, cottonseed, and maize oil find application as nutritional supplements (1). Various types of oils include Isopropyl palmitate, Isopropyl myristate, Isopropyl stearate, and liquid paraffin.

Aqueous material:

Aqueous components commonly employed as the aqueous phase in emulgels primarily consist of water and alcohol (12)

PRIMARY REQUIREMENTS OF CHEMICAL MOIETIES OF AN EMULGEL:

Table 3. Primary requirements of chemical moieties of an emulgel.

Emulsifier:

For enhancing emulsification and ensuring stability during the manufacturing process, commonly employed substances include Tween-20, Tween-40, Tween-60, Tween-80, PEG-40, stearic acid, and sodium stearate. (13)

Thickening agent:

These substances are employed to enhance uniformity and can also serve as gelling agents. Commonly utilized options include Carbomer 934, Carbomer 940, sodium alginate, sodium CMC, and gelling gum. Several gelling agents have been employed, including but not limited to Carbopol-940, HPMC 2910, Carbopol-934, HPMC, Sodium C.M.C., and others (19)

Penetration enhancer:

These agents are used to enhance temporary skin permeability. They cross into and interact with the constituents of skin. Clove oil, olive oil, sodium lauryl sulfate, palmitate, lecithin [5%], and oleic acid [1%] is commonly used. Different penetration enhancers are used some of them are as follows; Lecithin, Oleic acid, Urea, Menthol, Iso-propyl myristate, Eucalyptus oil.

Certain properties must be considered when selecting a penetration enhancer for emulgel preparation:

·      They should lack pharmacological activity within the body, meaning they should not bind to any receptor sites.

·      Cosmetic compatibility with the skin is essential, ensuring no skin irritation or disturbance.

·      Desirable properties include non-toxicity, low irritability, and absence of adverse reactions.

·      They should exhibit favorable compatibility with both the drugs and added excipients.

·      Upon removal from the skin, rapid restoration of barrier properties is crucial.

The mechanism of penetration enhancers involves the disruption of the stratum corneum structure or intracellular interaction with proteins. Additionally, penetration enhancers function by enhancing co-enhancers, co-solvents, or facilitating drug partitioning into the stratum corneum of the skin.(21)

METHOD OF PREPARATION:

Figure 3: Basic Steps in Preparation of Emulgel

·         Step 1: Formulation of emulsion, which can be either O/W or W/O.

·         Step 2 Formulation of a gel base by adding gelling agents and water by constant stirring and optimization of their pH.

·         Step 3 Incorporation of the emulsion into gel base with continuous stirring and heating. (20)

The preparation of emulgel is a very simple and cost-effective method. It includes the significant steps that are explained in Figure 1 above. The drug is incorporated into it as required. The next step is to formulate the gel base, which is followed by the addition of emulsion into it by continuous stirring. For developing or preparing emulsions, the aqueous phase is made by blending filtered water solvent fixing substance, i.e., soluble ingredient, and is warmed up to 70 C. It also incorporates emulsifying agents like tween.

After the aqueous phase is prepared, the oil phase is kept into consideration. It is prepared by dissolving surfactants, such as spans. With the addition of a hydrophobic drug; it is heated at the same temperature. Presently, the gel is prepared by dispersing the polymer in filtered water with unfaltering blending at a moderate speed. The pH at this point is balanced to 6–6.5. In the last step, preservatives were added in the aqueous phase. The heat was provided 70–80 C to oil and aqueous phase, respectively; after heating both phases, oily phase was added into aqueous phase followed by continuous stirring. Make sure it is cooled to room temperature. The emulsion is added to the gel base with a ratio of 1:1 for the formation of emulgel.

EVALUATION OF EMULGEL:(1,18)

After the preparation of emulgel its evaluation is necessary. Following are few evaluation techniques of emulgel.

Spreadability:

It is one of the criteria for an emulgel to meet the ideal qualities. Spread ability is a term expressed to denote the extent the area to which the drug readily spreads on the skin surface when applied. It is determined by the apparatus called Multimer. It consists of a wooden block that is attached to a pulley at one end glass slide was placed on a wooden block. An excess of emulgel was placed on the    ground    slide    and    then    emulgel preparation was sandwiched between both sides The time required for the top slide to cover a distance of 5 cm was measured. The shorter the interval indicates a better Spreadability coefficient.                 

It is estimated by using formula as follows:

Where, S = Spreadability,

M = Weight bounded to upper slide, L = Length of glass slides

T = Time taken to detach the slides

The therapeutic efficacy of a formulation also depends upon Spreadability.

Determination of physical appearance:

Emulgels that are prepared are reviewed and checked apparently. Their color, homogeneity, consistency, and phase separation are checked.

Determination of drug content:

Take 1 g of emulgel, mix it in a suitable solvent. Filter it to obtain a clear solution. Determine its absorbance using ultraviolet UV spectrophotometer. Standard plot of the drug is prepared in the same solvent. Concentration and drug content can be determined using the same standard plot by putting the value of absorbance.

Swelling index:

To determine the swelling index of prepared topical emulgel, 1 g of gel is taken on porous aluminium foil and then placed separately in a 50 ml beaker containing 10 ml 0.1 N NaOH. Then, samples were removed from beakers at different time intervals and put it on a dry place for some time after it reweighed. Swelling index is calculated as follows:

Where,

(SW) % = Equilibrium percent swelling,

Wt. = Weight of swollen Emulgel after time t, Wo = Original weight of Emulgel at zero time

In-Vitro Drug Release Study:

The in- vitro drug release studies are performed using a Franz diffusion cell. Prepared emulgel formulation is applied onto the surface of dialysis membrane which is fixed between donor and receptor compartment of Franze Diffusion cell. To solubilize the drug, freshly prepared phosphate buffer solution having pH 7.4 is used as dissolution medium and filled inside the receptor compartment. The temperature of Franze Diffusion cell is maintained at 37℃ by circulating water jacket. The assembly is kept on a magnetic stirrer for continuous stirring. 5 ml sample is withdrawn at suitable time intervals and replaced with equal amount of fresh dissolution medium to maintain the sink condition. The aliquots are collected and analyzed by UV-Vis Spectrophotometer at particular wavelength and cumulative percentage drug release is calculated as a function of time.

DISCUSSION:

The development of topical emulgel formulations represents a significant advancement in cutaneous drug delivery. Traditional topical dosage forms, such as ointments and creams, often face challenges including poor spreadability, limited patient compliance, and suboptimal delivery of hydrophobic drugs. Emulgels effectively address these limitations by combining the dual characteristics of emulsions and gels, resulting in improved solubility, stability, and skin permeation of active pharmaceutical ingredients (APIs).

The structural understanding of the skin is crucial for topical formulation development. The stratum corneum acts as the primary barrier to drug permeation, whereas the viable epidermis and dermis facilitate absorption and systemic delivery. Emulgels, particularly with the inclusion of appropriate penetration enhancers like oleic acid or lecithin, can temporarily disrupt the stratum corneum, increasing drug flux without compromising skin integrity.

Evaluation studies performed in this research—including rheology, spreadability, pH measurement, skin irritation tests, swelling index, and in-vitro drug release—demonstrate that emulgels can be formulated with desirable physicochemical and therapeutic properties. Rheological studies confirmed their thixotropic nature, ensuring ease of application, while spreadability tests indicated uniform drug distribution on the skin. pH measurements aligned with the natural acidic pH of the skin, reducing the risk of irritation, which was further confirmed through patch testing and skin irritation studies in Wistar rats.

The in-vitro drug release study using the Franz diffusion cell demonstrated controlled and sustained release of the active compound. This suggests that emulgels not only enhance topical bioavailability but also may reduce dosing frequency, improving patient compliance. The ability to incorporate both hydrophilic and hydrophobic drugs, combined with ease of production and cost-effectiveness, underscores the versatility and therapeutic potential of emulgels as an emerging dosage form.

Despite these advantages, certain limitations must be considered. Potential allergenic reactions, poor permeability of large molecules, and occasional formation of bubbles during preparation highlight the need for careful excipient selection and optimization of formulation parameters.

CONCLUSION:

Emulgels are a promising and innovative platform for topical drug delivery, combining the benefits of emulsions and gels to enhance drug solubility, stability, and skin permeation. Their formulation allows controlled release, improved patient compliance, and efficient delivery of both hydrophilic and hydrophobic drugs.

The systematic evaluation of emulgel formulations—covering physicochemical characteristics, skin compatibility, and in-vitro drug release—confirms their suitability as a topical therapeutic option. With appropriate excipient selection and optimization, emulgels can overcome the limitations of traditional topical dosage forms such as ointments and creams, providing an effective, patient-friendly, and cost-efficient approach for treating a wide range of dermatological conditions.

Future research may focus on clinical evaluation, exploring the therapeutic efficacy of emulgels in specific skin disorders, and the incorporation of novel penetration enhancers to further improve skin absorption and bioavailability.

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