Development of a Polymeric Transdermal Patch Containing Fulvic Acid: Formulation and In-Vitro Evaluation

Tanveer Aalam; Sanjay Dhaker; Ankita Raikwar; Dinesh Upadhyay; Subhranshu Panda

doi:10.5281/zenodo.20346979

Research Paper | Open Access
Volume 02 | Issue 05 | Article Id IJMPS/260205058

Development of a Polymeric Transdermal Patch Containing Fulvic Acid: Formulation and In-Vitro Evaluation
Tanveer Aalam* Sanjay Dhaker Ankita Raikwar Dinesh Upadhyay Subhranshu Panda
School of Pharmaceutical Sciences, Jaipur National University, Jaipur, Rajasthan

Abstract

The present study focused on the formulation and evaluation of a fulvic acid transdermal patch for controlled and sustained drug delivery through the skin. Transdermal drug delivery systems (TDDS) avoids of first-pass metabolism, improved patient compliance, sustained plasma drug concentration, and reduced gastrointestinal side effects. Fulvic acid, a naturally occurring humic substance, possesses significant antioxidant, anti-inflammatory, antimicrobial, and wound-healing properties. The transdermal patch was prepared using the solvent casting method employing polyvinyl alcohol (PVA) as the film-forming polymer, glycerin as a plasticizer, and oleic acid as a penetration enhancer. A polyester-based backing membrane was also prepared to provide mechanical support to the patch. The formulated patches were evaluated for physicochemical parameters including physical appearance, thickness, average weight, surface pH, drug content uniformity, and in-vitro dissolution studies. The prepared patches were smooth, flexible, and exhibited satisfactory film-forming characteristics. The average thickness of the patch was found to be 1.5 mm, while the surface pH was 6.3, indicating compatibility with skin and minimal irritation potential. The average weight uniformity confirmed consistency in formulation. In-vitro dissolution studies using phosphate buffer pH 7.4 demonstrated gradual and sustained drug release, with absorbance increasing from 0.08 at 15 minutes to 0.200 at 90 minutes. The controlled release behavior was attributed to the swelling and diffusion properties of the PVA matrix. The study concluded that the developed fulvic acid transdermal patch possesses suitable physicochemical characteristics and sustained drug release properties.

Keywords

Transdermal drug delivery system, Fulvic acid, Solvent casting method, Controlled drug release, Anti-inflammatory activity, Penetration enhancer, Wound healing

Introduction

Transdermal drug delivery systems (TDDS) are non‑invasive dosage forms designed to deliver a therapeutically effective amount of drug directly through the skin, either into the systemic circulation for systemic action or into the underlying skin layers for local effect. Unlike oral or injectable routes, TDDS uses the skin as a controlled reservoir, enabling sustained plasma levels and reducing dosing frequency and gastrointestinal side effects [1, 2, 3, 4]. The key route of transport of the drug is through the stratum corneum, the highly keratinized outer layer of the epidermis, which acts as the main barrier limiting drug permeation. Only drugs with appropriate physicochemical properties, low molecular weight, balanced lipophilicity–hydrophilicity, and small dose requirement can pass efficiently through this barrier without special techniques [1, 4, 5].

Types of TDDS

Basic TDDS types include single‑layer matrix, multi‑layer matrix, reservoir, and drug‑in‑adhesive patches, as well as newer approaches like microneedles, iontophoresis, sonophoresis, and nano‑based carriers (liposomes, niosomes, ethosomes) that enhance permeation [1, 3, 6].
Clinically used examples include nicotine patches for smoking cessation, hormone patches (estradiol, testosterone), opioid analgesics (fentanyl, buprenorphine), anti‑emetics, and local‑anesthetic patches (e.g., lidocaine) [1, 3].

TDDS avoids first‑pass metabolism and GI degradation, provides steady, controlled drug release over hours to days, improving patient compliance and reducing peak‑trough fluctuations and non‑invasive, self‑applicable, and suitable for drugs with short half‑lives [1, 3, 4]. Whereas, it does also have some limitations that include low permeability for large or highly hydrophilic molecules, skin irritation or sensitization in some patients, relatively low drug‑loading capacity and higher development cost for advanced enhancers or patches [1, 3, 6].

TDD offers several important pharmacological and patient‑oriented advantages over conventional oral or injectable routes. Below is a concise overview of its key benefits. It avoids first‑pass metabolism and GI degradation By delivering drug directly through the skin into the systemic circulation, TDD bypasses the liver’s first‑pass effect and gastric/intestinal degradation, which is especially useful for drugs with poor oral bioavailability or high hepatic metabolism [3, 4, 7]. Has controlled and sustained release, many transdermal systems (patches, gels, films, etc.) provide slow, continuous release over hours to days, maintaining more stable plasma concentrations and reducing side effects from sharp peaks and troughs [7, 8, 9]. Improved patient compliance and convenience
Patches and topical systems are non‑invasive, easy to apply, and often self‑managed at home, which improves adherence, particularly in chronic diseases (e.g., hypertension, pain, hormone therapy) [7, 10]. Reduced gastrointestinal side effects Because the drug does not pass through the GI tract, TDD minimizes nausea, vomiting, gastric irritation, and other enteric‑related adverse effects [7, 9]. Less painful and minimally invasive Compared with injections, most transdermal systems are pain‑free or low‑pain, and new technologies like microneedles can deliver larger‑molecule drugs without significant discomfort [7, 9]. Potential for local as well as systemic action Depending on the carrier and drug, transdermal delivery can be used either for systemic effects (e.g., nicotine, fentanyl, hormones) or for local treatment (e.g., analgesic or anti‑inflammatory patches for musculoskeletal pain or skin‑related conditions) [3, 4, 9].

Figure No. 1: Different layers of transdermal patches and layers of skin

Fulvic acid is a naturally occurring class of low‑molecular‑weight organic compounds derived from humic substances, widely studied for its biological activity and emerging therapeutic potential. It is increasingly used in nutrition, agriculture, and experimental pharmacology due to its antioxidant, anti‑inflammatory, and metal‑chelating properties [11,12, 13, 14]. It occurs naturally in soils, peat, compost, humus, lakes, and mineral‑rich deposits such as shilajit, a resin‑like substance from Himalayan and mountain‑range rocks that has been used in Ayurvedic and traditional medicine for centuries. It is highly water‑soluble, carries a negative charge, and contains abundant carboxyl and hydroxyl groups, which confer strong chelating capacity and high ion‑exchange and conductive properties [11, 12, 15]. Fulvic acid is strong antioxidant and free‑radical scavenging: Fulvic acid neutralizes reactive oxygen species and reactive nitrogen species, reducing oxidative stress in vitro and in animal models [11, 13, 16]. It has metal‑chelating and mineral‑transport action and hence forms stable complexes with metals and trace minerals, improving their bioavailability in plants and animals and aiding in detoxification [11, 12, 15]. FA is also a strong anti‑inflammatory and immunomodulatory effects therby in some preclinical and some clinical studies show suppression of pro‑inflammatory mediators (e.g., COX‑2, cytokines) and modulation of immune‑cell activity [12, 13, 17]. Heance Fulvic acid is widely used in chronic inflammatory and metabolic disorders like diabetes, atherosclerosis, and inflammatory diseases [12, 13]. Neuroprotection and cognitive disorders, studies indicate that fulvic acid can inhibit aggregation of pathological proteins (e.g., tau) in Alzheimer’s‑related models, supporting its investigation as a neuroprotective or cognitive‑enhancing supplement [12, 16], antimicrobial and infection‑related effects [12, 17]. And is a nutritional supplement and functional‑food ingredient: Fulvic‑acid‑rich beverages and mineral‑food supplements are marketed for improving mineral absorption, antioxidant status, and general vitality, although robust human‑dose‑response data are still limited [11, 12]. A transdermal patch based on fulvic acid is rationalized by its unique combination of low‑molecular‑weight structure, skin‑penetrating capacity, and broad biological activity (antioxidant, anti‑inflammatory, mineral‑chelating, and antimicrobial), which together make it a promising candidate for sustained, non‑invasive delivery to treat chronic inflammatory and skin‑related disorders [13]. It has favorable physicochemical profile since fulvic acid is a small, water‑soluble, hydrophilic organic acid with low molecular weight, enabling relatively deep penetration into the skin layers and sustained diffusion from a patch matrix [11, 18]. It has skin‑targeted and systemic effects hence when applied topically, it can simultaneously modulate oxidative stress, inflammation, and microbial load in the skin, while transdermal delivery can also support systemic effects (e.g., anti‑arthritic, neuroprotective, or metabolic actions) without first‑pass metabolism [13, 18]. It is naturally safe, and consumer‑accepted carrier as a natural humic‑derived component, fulvic acid offers a “green” alternative to synthetic permeation enhancers and aligns with growing demand for plant‑based and eco‑friendly delivery systems [12, 20, 21]. Recent work on fulvic acid transdermal patches shows that, with proper optimization of isolation (water‑soluble polymorph) and polymer matrix (e.g., Pluronic‑based systems), controlled release and feasible skin permeation of fulvic acid can be achieved [19, 22]. However, robust clinical data are still limited, and there is a clear need for well‑characterized transdermal patches with defined release kinetics and stability profiles [18, 22]. Studies specifically testing anti‑inflammatory and wound‑healing endpoints in chronic‑pain or inflammatory‑skin models (e.g., arthritis, atopic dermatitis, acne, or diabetic‑wound‑related irritation) [13, 19].

METHODOLOGY

A. Preparation of Transdermal Patch

Table No. 1: Composition of ingredients and functions of chemicals in transdermal patches

S. No	Ingredients	Function	Quantity
1	Fulvic Acid	Antioxidant, anti- inflammatory, wound healing	1g
2	Polyvinyl Alchol(PVA )	Film- forming agent	5g
3	Glycerin	Plasticizer	1 ml
4	Oleic Acid	Penetration enhancer	1 ml
5	Distilled Water	Solvent	q.s

1. Preparation of Polymer Solution: 5 g of polyvinyl alcohol (PVA) (5 g) was dissolved in 100 ml distilled water (q.s.) under continuous stirring until a clear and homogeneous solution was obtained.

2. Drug Incorporation: 1g fulvic acid was dissolved in 100 ml of distilled water, and added to polymer solution with continuous stirring to ensure uniform distribution of the drug throughout the matrix system.

3. Addition of Plasticizer: 1ml glycerin was added to the polymer-drug solution and mixed thoroughly to enhance the flexibility of the film and prevent brittleness.

4. Addition of Penetration Enhancer: 1ml of Oleic acid was added to the above mixture as a penetration enhancer and stirred continuously until a homogeneous mixture was formed.

5. Casting of Film: The prepared solution was poured onto a clean and leveled petri dish and spread uniformly to obtain a film of consistent thickness.

6. Drying: The cast film was dried at room temperature for 24 hours to allow complete evaporation of the solvent, resulting in the formation of a uniform and flexible transdermal patch.

Figure No. 2: Transdermal patch spread over petridish.

B. Preparation of Backing layer

Table No. 2: Composition of ingredients and functions of chemicals used in backing membrane

S.No	Ingredients	Function	Quantity
1.	Polyester	Film forming agent	5g
2.	Toluene	Solvent	100ml

1. Formation of Polymer Solution: 5g of polyester polymer was dissolved in 100 ml of toluene under continuous stirring until a clear solution was obtained.

2. Addition of Plasticizer: 3ml of glycerin was added to the polymer solution and mixed thoroughly to improve the flexibility and mechanical strength of the backing layer.

3. Casting of Film: The prepared solution was poured into a clean petri dish and spread evenly to ensure uniform thickness of the film.

4. Drying: The film was dried at room temperature for 24 hours to allow complete evaporation of the solvent. The dried backing layer was then carefully removed and stored for further use [23].

Figure No. 3: Backing membrane spread over a stable platform

Figure No. 4: Formulated transdermal patch

RESULTS AND DISCUSSION

1. Physical Appearance

The prepared transdermal patches were smooth and flexible [24].

2. Thickness of Patch

The thickness of the patches was measured using a digital vernier calliper at three different positions, and the average value was calculated [25].

Table No. 3: Thickness measurement of patch

Thickness	Main scale reading	V. scale reading(n)	*nLeast count**
t₁	0.1cm	5	0.05
t₂	0.2cm	5	0.05
t₃	0.01	6	0.06

Total thickness =0.15cm or 1.5mm

This shows the ideal thickness of the patch [26].

3. Average Weight

Individual patches of a defined size were cut and weighed using a digital balance. The average weight was calculated.

Table No. 4: Average weight calculation of patches

Weight	Films
W₁	0.014
W₂	0.218
W₃	0.015

Total weight= 0.082 and shows ideal weight for uniform patch [27].

4. Surface pH- Placed film in distilled water for 30 mins and measure pH using digital pH meter. The pH of a film is 6.30 this shows it is compatible to skin [28].

5. Drug content uniformity- The drug was dissolved in a Phosphate buffer solution[7.4pH]. The solution was filtered and analyzed using UV-visible spectrophotometry at the appropriate wavelength. The drug content was calculated [29, 32, 33].

(a) Standard drug

Dissolution -The in-vitro dissolution study of the prepared transdermal patches was carried out using dissolution test apparatus with phosphate buffer (pH 7.4) as the receptor medium [30, 31, 34].

Table No. 5: Dissolution profile of patches

Time [Mins]	Absorbance
0	0
15	0.08
30	0.091
45	0.100
60	0.102
75	0.197
90	0.200

The dissolution profile demonstrated a gradual and sustained release of fulvic acid from the transdermal patch matrix. Initially, the drug release was slow, with absorbance values increasing from 0.08 at 15 minutes to 0.102 at 60 minutes, indicating controlled diffusion of the drug through the polymeric matrix. A comparatively higher increase in absorbance was observed at 75 minutes (0.197) and 90 minutes (0.200), suggesting enhanced release of the entrapped drug at later stages of dissolution. This sustained release pattern may be attributed to the hydrophilic nature of polyvinyl alcohol (PVA), which gradually swells in the dissolution medium and allows controlled diffusion of fulvic acid.

CONCLUSION

The present study successfully demonstrated the preparation and characterization of a fulvic acid transdermal patch using the solvent casting technique [18]. The formulated patch containing polyvinyl alcohol (PVA), glycerin, and oleic acid showed satisfactory physicochemical and mechanical properties suitable for transdermal drug delivery applications. The prepared patches were smooth, flexible, and exhibited uniform thickness, weight variation, and drug distribution, indicating consistency in formulation [35]. The surface pH of the patch was found to be compatible with skin, suggesting minimal risk of irritation during topical application [36]. In-vitro dissolution studies confirmed sustained and controlled release of fulvic acid over an extended period, while the incorporation of oleic acid effectively enhanced drug permeation through the membrane. The formulation also demonstrated acceptable stability and good film-forming characteristics [37]. Fulvic acid possesses significant antioxidant, anti-inflammatory, antimicrobial, and wound-healing activities, which make it a promising therapeutic agent for transdermal delivery [38]. The developed transdermal patch offers several advantages such as improved bioavailability, avoidance of first-pass metabolism, prolonged drug release, and enhanced patient compliance compared to conventional dosage forms [39]. Overall, the study concludes that the formulated fulvic acid transdermal patch is a stable, safe, and effective drug delivery system with potential applications in the management of inflammatory conditions, wound healing, and skin-related disorders. Further pharmacological and clinical investigations may be carried out to establish its therapeutic efficacy and long-term safety for commercial and clinical applications [19].

ACKNOWLEDGMENT

The authors express their sincere gratitude to the School of Pharmaceutical Sciences, Jaipur National University, Jaipur, for providing the necessary facilities and support to carry out this research work. The authors also thank the faculty members and laboratory staff for their guidance and assistance throughout the study.

CONFLICT OF INTEREST

The authors declare that there is no conflict of interest regarding the publication of this research work.

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