Topical delivery refers to medications that are applied directly to the skin to treat various skin conditions. Unlike pills or injections that travel through your entire body, these treatments work specifically on the area where they're applied. For instance, if you're treating acne or psoriasis, the medicine works directly on those affected skin areas without spreading throughout your body. Healthcare providers and patients can choose from various types of topical treatments. These include everyday items like creams and lotions, medicated ointments, liquid solutions, powders, and spray medications.[1] Each type is designed for specific uses and skin conditions, giving doctors and patients multiple treatment options.  The main advantage of topical treatments is their ability to target specific skin areas while minimizing how much medicine enters the bloodstream.[2] This targeted approach helps reduce potential side effects that might occur if the medicine were to spread throughout the body.[2] It's similar to how sunscreen works - providing protection exactly where it's needed. However, traditional topical treatments do have their drawbacks. Creams and ointments can feel greasy or sticky on the skin. Some lotions might stain clothing or require frequent reapplication to remain effective. These limitations have encouraged researchers to continue developing new and improved forms of topical medications that are both more effective and more comfortable for patients to use.[3]  Traditional skin treatments often come with a few drawbacks that can make them less comfortable to use. Imagine trying to spread thick honey on your skin—it’s sticky, hard to spread, and requires a lot of rubbing to cover a large area. Many ointments and creams feel like this, which can be off-putting for patients.[4] On top of that, these products don’t always stay stable over time, which can reduce their effectiveness. This is where transparent gels came into play.[5] They offered a better alternative because they were lighter and easier to apply, making them popular in both skincare and medicinal products. However, gels had their own limitations. They couldn’t effectively carry certain types of medications, especially those that don’t mix well with water. Then, scientists came up with a clever solution: combining the best of both worlds—gels and emulsions. This new formulation, known as "emulgel," delivers the smooth, lightweight feel of a gel, but with the added benefit of being able to carry a wider range of medications, including those that aren’t water-soluble. Imagine mixing the soothing feel of aloe vera gel with the rich delivery power of a cream. The result is something that’s not only easy to apply but also more effective at getting the medicine where it’s needed. This innovation has led to skin treatments that are both patient-friendly and therapeutically potent.

1. 1. Gels As Pharmaceutical Dosage Forms

The term "gel" was first introduced in the late 1800s to describe certain semisolid materials based on their physiological properties rather than their molecular composition.[6-8] According to the U.S. Pharmacopeia (USP), gels are defined as semisolid systems composed of dispersions containing either small inorganic particles or large organic molecules, which are surrounded and interpenetrated by a liquid.[9-13] Gels are highly diluted cross-linked systems that remain stationary and do not flow when in a steady state.[14-15]Gels are two-component semi-solid systems with a high liquid content. A defining characteristic is their continuous structure, which imparts solid-like properties. [16-17] The biocompatibility, network structure, and molecular stability they offer for incorporated bioactive agents have made gels a leading material in drug delivery formulations.[17]

1.2 Emulsion and Gel Combination in Pharmaceutical Dosage Forms

Emulgels, as their name implies, combine gel and emulsion properties.  These oil-in-water or water-in-oil emulsions effectively deliver drugs to the skin, exhibiting high skin penetration.  The addition of a gelling agent to the water phase transforms a standard emulsion into an emulgel.[17-20]  For dermatological applications, emulgels offer several advantages: thixotropy, a greaseless and easily spreadable/removable texture, emollience, lack of staining, water solubility, extended shelf life, biocompatibility, transparency, and an aesthetically pleasing appearance.  Skin penetration occurs via three routes: the intact stratum corneum (accounting for over 99% of the skin surface and representing the rate-limiting step), sweat ducts, and sebaceous follicles.  Percutaneous absorption involves three key processes: establishing a concentration gradient (the driving force), drug release from the emulgel (partition coefficient), and drug diffusion through skin layers (diffusion coefficient).[21]

2. MATERIALS AND METHOD

Gentamicin was provided by Arco Lifesciences, Nagpur (INDIA) Carbopol 934, Carbopol 940, HPMC (S.D fine chemicals Pvt. Ltd, Mumbai). Sodium Borohydrate procure from HiMedia Laboratories Private Limited, Thane (West) Mumbai (INDIA) All other chemicals and reagents used were of analytical grade. Deionized distilled water was used throughout the study.

3. Solubility study:

Gentamicin solubility was determined in phosphate buffer, distilled water, 5% triethanolamine solution, and a chloroform-water solution using the shake flask method[22].  Specifically, an excess of gentamicin was added to 10 mL of each solvent in separate vials.  The mixtures were agitated mechanically for 72 hours at 25°C using an isothermal shaker.  Following agitation, the samples were filtered using Whatman filter paper before UV analysis to determine the amount of gentamicin dissolved in each solvent.  This analysis will identify which solvent provides the best solubility for gentamicin.

 4. Preparation of Rice Bran Wax

4.1 Purification of rice bran wax:

40 grams of raw wax were added to 200 mL of water in a round-bottom flask (RBF) and heated to 80°C using a heating mantle.  Sodium borohydride was then added dropwise.  The resulting resinous matter settled in the RBF.  The wax was subsequently filtered and allowed to cool to room temperature. After 2–4 hours, the solidified wax was collected to remove residual moisture, yielding moisture-free wax for further experimentation.[21]

4.2 Saponification of Rice bran wax

Two grams of rice bran wax (RBW) were added to a 200 mL flask containing 40 mL of ethanolic potassium hydroxide.  The mixture was refluxed for two hours with frequent swirling. While still hot, the excess alkali was titrated with 0.5 M hydrochloric acid, using phenolphthalein as an indicator. A blank titration (without RBW) was performed. The saponification value was then calculated using the formula:

Saponification Value = 28.05x(B-A)w

4.3 Physicochemical Properties of Crude and Purified Rice Bran Wax

Table no 1 Physiochemical Properties.

The physicochemical properties of both crude and purified rice bran wax.  The melting point of the crude wax was 62°C, increasing to 80°C after purification.  Similarly, the acid value decreased significantly from 8.3 to 1.6, and the saponification value dropped from 141 to 82.  Finally, the iodine value, an indicator of unsaturation, also decreased substantially, from 41 to 8.0 following purification.

4.4 Different Surfactant Blends

Table 2: Different surfactant blend of Emulsions.

Table 2 summarizes the stability study of eight emulsions, each prepared with a different hydrophile-lipophile balance (HLB) value ranging from 8 to 15. The observations indicate that all prepared emulsions were stable; however, the emulsion with an HLB value of 12 was highlighted as the preferred formulation because its HLB falls within the optimal, median range for stability [22].

4.5 Stability Study of Emulsions

Table 3: Stability Study

A stability study was conducted on eight emulsions, each formulated with a different hydrophile-lipophile balance (HLB) value, ranging from 8 to 15.  The results showed that all emulsions were stable.  However, the emulsion with an HLB of 12 was deemed optimal because its HLB value lies within the median range, suggesting enhanced stability compared to emulsions with higher or lower HLB values.

4.5 HLB Photomicroscopic Images

Table no 4 Photomicroscopic images of Emulsions

Photomicrographic analysis of emulsions with HLB values ranging from 8 to 15 (Emulsions 1-8) revealed a consistent pattern:  in all cases, the internal phase globules were evenly distributed throughout the slide, indicating the formation of homogeneous emulsions across the tested HLB range[23].

5. Preparation of Emulgel :-

An emulsion was prepared by combining 100 mg of drug, 1 g of saponified wax, and 1 g of surfactant blend in a sufficient quantity of ethanol. Ten milliliters of water were added, and the mixture was stirred for 10 minutes to form an emulsion. Separately, a gel base was prepared by slowly incorporating Carbopol into distilled water with continuous stirring, allowing it to hydrate overnight. Finally, the prepared emulsion was incorporated into the gel base with moderate stirring, and the pH was adjusted to 6.0-6.5 using triethanolamine (TEA).

Table no 5: Composition of Gentamicin Emulgel

6. Evaluation Of Emulgel

6.1 Physical Examination

The Prepared Emulgel Formulations Were Inspected Visually For Their Color, Appearance And Consistency. [23]

6.2 Rheological Study

Viscosity Measurements Were Obtained Using A Brookfield Cone And Plate Viscometer (Spindle 7) At 25°C.  The Viscometer Was Connected To A Circulating Water Bath For Temperature Control.  The Emulgel Sample Was Placed In A Temperature-Controlled Beaker, The Spindle Was Inserted, And The Viscosity Reading Was Recorded.

6.3 Ph Detection :

The Ph Of The Formulated Batches Was Measured Using A Calibrated Ph Meter At 25°C.  The Electrode Was Carefully Immersed Into The Emulgel Sample, And The Ph Reading Was Recorded After Stabilization.

6.4 Extrudability Measurement

Extrusion Force Was Measured Using A Extrusion Rheometer At 25°C. The Instrument Was Equipped With A  Probe And Connected To A Temperature-Controlled Environment.  The Emulgel Sample Was Loaded Into The Barrel, Placed In A Temperature-Controlled Chamber And The Extrusion Force Was Recorded.

6.5 Spreading Coefficient

To Measure The Spreadability Of The Emulgel, We Followed A Method Described By Mutimer.  This Involved A Simple Yet Effective Apparatus.  First, We Placed Approximately Two Grams Of The Emulgel Onto A Horizontal Ground Glass Slide Which Was Secured To A Wooden Block Connected To A Pulley System.  This Ensured A Consistent Starting Point For The Test.  A Second, Identical Ground Glass Slide Was Carefully Placed On Top Of The Emulgel, Creating A Sandwich. A 500-Milligram Weight Was Placed On The Top Slide For Five Minutes.  This Step Served A Dual Purpose: It Expelled Any Trapped Air Bubbles Between The Slides, Leading To A Uniform Emulgel Film, And It Also Applied A Slight Initial Pressure To Compress The Emulgel, Creating Consistent Starting Conditions For Our Spreadability Test. After The Five-Minute Compression Period, A Measured Additional Weight Was Added To The Top Slide, Which Was Attached Via A Small Hook To The Pulley System. The Time It Took For The Weighted Top Slide To Slide 5 Centimeters Across The Lower Slide Was Then Precisely Recorded.  This Measurement Provided A Quantitative Measure Of Spreadability. The Underlying Principle Is That A Shorter Time To Cover The 5-Centimeter Distance Indicates A Lower Resistance To Spreading, Meaning That The Emulgel Possesses A Superior Spreading Coefficient.  Essentially, The Lower The Drag And The Greater The Slip, The Faster The Top Slide Moves And The Better The Emulgel's Spreadability.[25]

6.6 Bioadhesive Strength Measurement

Bioadhesive Strength Was Measured Using A Modified Two-Arm Balance Method.  Two Glass Slides, Each Holding A Piece Of Rat Skin, Were Balanced Against A Single Weighted Glass Slide.  One Gram Of Emulgel Was Placed Between The Skin-Bearing Slides, And Pressure Was Applied To Remove Air. Weight Was Then Gradually Added (200 Mg/Minute) To The Opposite Pan Until The Slides Separated.  The Weight Required To Detach The Slides Provided A Measure Of The Emulgel's Bioadhesive Strength[26].

The Bioadhesive Strength Is Calculated By Using Following:

Biodhesive Strength = Weight Required (In G)  / Area (Cm²)

6.7 In Vitro Release Studies:

The In Vitro Drug Release Studies Were Carried Out Using A Modified Franz Diffusion (FD) Cell. The Formulation Was Applied On Dialysis Membrane Which Was Placed Between Donor And Receptor Compartment Of The FD Cell. Phosphate Buffer Ph 7.4 Was Used As A Dissolution Media. The Temperature Of The Cell Was Maintained At 37 C By Circulating Water Jacket. This Whole Assembly Was Kept On A Magnetic Stirrer And The Solution Was Stirred Continuously Using A Magnetic Bead. A Similar Blank Set Was Run Simultaneously As A Control. Sample (5 Ml) Was Withdrawn At Suitable Time Intervals And Replaced With Equal Amounts Of Fresh Dissolution Media. Samples Were Analyzed Spectrophotometrically At 224 Nm And The Cumulative % Drug Release Was Calculated. The Difference Between The Readings Of Drug Release And Control Was Used As The Actual Reading In Each Case.[27]

6.8 In Vitro Anti-Bacterial And Antifungal Activity:-

In Vitro Antibacterial Activity Of Emulgel Was Assessed By The Disc Diffusion Method Against Three Strains Of Bacteria: Staphylococcus Aureus, Streptococcus Pyogen, Pseudomonas Aeroginosa And Against Candida Albican Was Expressed As Diameter Of The Inhibition Zones[28-30].

7. RESULT AND DISCUSSION

7.1 Physical Appearance

Emulgel Formulations Were Yellowish White Viscous Creamy Preparation With A Smooth Homogeneous Texture And Glossy Appearance. Results Have Been Discussed In Table No 6

Table No. 6 Physical Appearance

7.3 Bioadhesive strength measurement

The bioadhesive strength of various emulgel formulations have been shown below in Fig. 3.

Formulations F1, F2, and F3 exhibited distinct drug release profiles over 120 minutes.  F1 consistently demonstrated the highest cumulative drug release at each time point, reaching 84.15% by 120 minutes. F2 showed a slower release, reaching 61.06% at 120 minutes, while F3 displayed a relatively lower and less variable release profile, reaching 54.55% at 120 minutes. Result have been shown in Table no 8 , Fig no 4[31-33]

Table no 8 In vitro drug Release Study

       
           
       
Fig no 4 In-Vitro Drug Release