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Permeation improvement and prolonged skin deposition of silymarin through shatdhauta ghrita cream: Formulation, dermatokinetic and anti-aging studies

This study demonstrates that formulating silymarin in a traditional Shatdhauta ghrita cream significantly enhances its skin permeation and deposition, prolongs its stability, and effectively exerts anti-aging effects by reducing oxidative stress markers while boosting antioxidant enzymes and collagen levels.

Original authors: Moreshwar Patil, Madhuri Deshmukh

Published 2026-07-01

📖 4 min read☕ Coffee break read

CC BY 4.0

Original authors: Moreshwar Patil, Madhuri Deshmukh

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

The Big Idea: A "Super-Soaker" for Skin Creams

Imagine your skin is a very tough, brick-walled fortress. Most creams are like water balloons; they hit the wall and splash off, never getting inside to do their job. The drug in this study, Silymarin (a powerful plant extract known for fighting aging), is like a valuable treasure that is stuck inside a heavy, waterproof box. It can't get through the fortress walls on its own because it doesn't mix well with water and is too big to slip through the cracks.

The researchers wanted to build a special delivery vehicle to get this treasure inside the fortress. They chose an ancient Ayurvedic ingredient called Shatdhauta Ghrita (SDG).

What is Shatdhauta Ghrita?

Think of SDG as "super-churned butter." It is made by taking clarified butter (ghee) and washing it with water 100 times.

The Analogy: Imagine taking a lump of clay and kneading it with water over and over again until it breaks down into tiny, invisible specks. This process splits the fat molecules apart, turning a thick, heavy substance into a silky, ultra-fine emulsion.
The Result: Instead of a thick layer of grease sitting on top of the skin, SDG creates a "micro-sponge" that is so fine it can slip through the skin's defenses easily.

The Experiment: Building the "Anti-Aging Truck"

The researchers loaded the Silymarin treasure into this SDG "truck" and tested it against a standard, store-bought cream. Here is what they found:

1. The Texture Test (The "Spreadability" Race)

The Claim: The new cream was much smoother and easier to spread.
The Analogy: If the store-bought cream was like trying to spread thick peanut butter with a butter knife, the new SDG cream was like spreading warm honey. It flowed effortlessly.
The Science: The SDG cream had much smaller "droplets" (particles) than the store-bought version. Because the particles were so tiny, the cream felt softer and didn't drag on the skin.

2. The Permeation Test (The "Tunnel" Race)

The Claim: The Silymarin in the SDG cream got through the skin barrier much faster and in larger amounts.
The Analogy: Imagine the skin is a crowded hallway. The store-bought cream is like a group of people trying to walk through the hallway while holding giant umbrellas (they get stuck). The SDG cream is like a group of ninjas who can slip through the gaps between the people.
The Data: Over 8 hours, the SDG cream delivered three times more Silymarin through the skin than the store-bought cream. It didn't just sit on the surface; it actually penetrated deep into the layers.

3. The "Anti-Aging" Power (The "Firefighters")

The Claim: The cream was excellent at fighting "rust" in the skin.
The Analogy: Sunlight and pollution create "rust" in your skin cells (called Free Radicals). This rust causes wrinkles and aging. Antioxidants are like firefighters that put out the rust.
The Result: When they tested the cream on skin cells, it acted as a super-firefighter. It reduced the "rust" (MDA and NO levels) and boosted the skin's own defense systems (SOD and Glutathione). It also helped the cells produce more collagen, which is the "scaffolding" that keeps skin firm and bouncy.

4. The "Deep Storage" Test (Dermatokinetics)

The Claim: The drug didn't just pass through; it stayed in the skin where it was needed.
The Analogy: Some delivery trucks drop the package at the front door and leave. The SDG cream is like a delivery service that drops the package in the basement and the attic, ensuring the whole house gets the goods.
The Data: The study showed that the Silymarin built up high concentrations in both the outer layer (epidermis) and the deeper layer (dermis) of the skin, staying there longer than the other cream.

5. The "Shelf-Life" Test

The Claim: The cream didn't go bad.
The Analogy: They left the cream in a hot room and a cool room for two months. It didn't separate, change color, or lose its power.
The Result: The cream is stable and has a predicted shelf life of about 1.26 years.

The Bottom Line

The researchers concluded that Shatdhauta Ghrita is a magical delivery system. It takes a difficult-to-use ingredient (Silymarin) and turns it into a cream that:

Spreads easily.
Slips deep into the skin (instead of sitting on top).
Fights aging effectively by boosting the skin's natural defenses.
Stays stable on the shelf.

In short, they proved that this ancient method of washing butter 100 times creates a modern, high-tech vehicle for delivering anti-aging medicine right where it needs to go.

Technical Summary: Permeation Improvement and Prolonged Skin Deposition of Silymarin through Shatdhauta Ghrita Cream

Problem Statement
Skin aging is driven by intrinsic and extrinsic factors, particularly solar radiation (UVA/UVB), which generates reactive oxygen species (ROS). These ROS cause oxidative stress, leading to the degradation of collagen, loss of skin firmness, and barrier dysfunction. Silymarin (SMN), a flavonoid complex with known antioxidant and anti-inflammatory properties, is a promising candidate for topical anti-aging therapy. However, its clinical utility is limited because it is classified as a BCS Class IV drug, characterized by low water solubility and poor skin permeability. Consequently, there is a need for a vehicle capable of enhancing SMN permeation and ensuring its deposition in the deeper epidermal and dermal layers.

Methodology
The study developed a topical cream formulation by incorporating silymarin into Shatdhauta Ghrita (SDG), a traditional Ayurvedic base prepared by washing clarified butter (ghee) with water 100 times. This process is intended to split fats and create a fine, non-oily emulsion.

The research methodology included:

Formulation: Preparation of SMN-loaded SDG cream with preservatives and pH adjustment.
Physicochemical Characterization: Evaluation of organoleptic properties, pH, viscosity, spreadability, particle size (via dynamic light scattering), and texture profile analysis (TPA) for hardness, cohesiveness, and work of cohesion.
Analytical Validation: Development and validation of an HPLC method for silymarin quantification.
Permeation Studies: In-vitro permeation through cellophane membranes and ex-vivo permeation through excised goat skin using Franz diffusion cells.
Dermatokinetics: Assessment of drug deposition in epidermal and dermal layers over 8 hours to determine $C_{Skin\ max}$ , $T_{Skin\ max}$ , and $AUC_{0-8h}$ .
Biological Evaluation:
- In-vitro antioxidant activity via DPPH radical scavenging assay.
- Skin irritation testing in Wistar rats (OECD-402 guidelines).
- Anti-aging efficacy on neonatal mouse dermal fibroblast cells, measuring biomarkers including Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione (GSH), and collagen levels after oxidative stress induction ( $H_2O_2$ ).
Stability: Storage studies at 30°C and 35°C for 60 days to determine shelf life.

Key Results

Physicochemical Properties: The developed cream was homogeneous with a pH of 6.4 ± 0.01 and a viscosity of 10,601 ± 0.57 cps. It exhibited superior spreadability (16.50 g.cm/sec) compared to a marketed formulation (21.63 g.cm/sec) and a significantly smaller particle size (486 nm vs. 1944 nm). TPA analysis indicated the SDG cream was softer (lower firmness) and less tacky than the marketed product.
Permeation: The SDG base significantly enhanced drug flux. Over 8 hours, the cumulative permeation through skin was 364.13 µg/cm² for SMN-SDG cream versus 134.76 µg/cm² for the marketed cream. The average flux through skin was 45.51 µg/cm²/h for SMN-SDG compared to 16.84 µg/cm²/h for the control.
Dermatokinetics: The SMN-SDG formulation demonstrated higher drug deposition in both the epidermis and dermis. The $C_{Skin\ max}$ in the epidermis was 180.88 µg/cm² (vs. 95.69 µg/cm² for marketed) and in the dermis was 192.15 µg/cm² (vs. 90.64 µg/cm²). The Area Under the Curve (AUC) was also significantly higher, indicating prolonged exposure.
Antioxidant and Anti-Aging Activity: The SMN-SDG cream showed a DPPH scavenging activity of 96.07%, comparable to ascorbic acid (98.41%). In cell line studies, the formulation significantly decreased MDA and Nitric Oxide (NO) levels while increasing SOD, GSH, and collagen levels compared to controls (p < 0.05). The EC50 value for the SMN-SDG cream (26.65 µg/ml) was lower than the base or silymarin alone, suggesting a synergistic effect.
Safety and Stability: The formulation was non-irritating in rat models. Stability data indicated the cream remained physically and chemically stable over 60 days, with a calculated shelf life of 1.26 years.

Significance and Claims
The authors conclude that Shatdhauta Ghrita serves as an effective vehicle for delivering poorly soluble and low-permeability drugs like silymarin. The study claims that the specific preparation method of SDG (100 washes) reduces droplet size and increases surface area, thereby acting as a permeation enhancer. The formulation successfully improved the skin deposition of silymarin and potentiated its antioxidant and anti-aging effects compared to a marketed formulation. The paper asserts that this traditional base can be effectively utilized to overcome the rate-limiting steps of absorption for hydrophobic phytoconstituents, offering a stable and effective topical solution for skin aging.

The Big Idea: A "Super-Soaker" for Skin Creams

What is Shatdhauta Ghrita?

The Experiment: Building the "Anti-Aging Truck"

The Bottom Line

Technical Summary: Permeation Improvement and Prolonged Skin Deposition of Silymarin through Shatdhauta Ghrita Cream

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