Formulation And Evaluation of Transdermal Patches from Thespesia Populnea for Anti-Inflammatory Activity

Thespesia populnea Linn, also known as the Portia tree, is a plant used in traditional medicinal formulations for its pharmacological and Therapeutic properties^[1] Thespesia populnea (Malvaceae) is a small evergreen tree ranging from 6-10m (20-30ft) in height. The trees grow well in warm coastal areas from the east coast of Africa and South and Southeast Asia to Melanesia. The Trees grow best under full sunlight and also tolerate drought conditions^[2].It propagates easily and grows rapidly. The plant is Astringent, Cooling, Anti-inflammatory, anti-diarrhoeal and Antibacterial. It is useful in Dysentery, Diabetes, and Haemorrhoids. Also cures Ulcers, itching, scabies and other skin diseases^[3].

PLANT PROFILE:

Botanical Name: T. Populnea Linn

Common name: Portia Tree.

Author: Linn.

Year: 2006

Synonym: Hibiscus bacciferus, Hibiscus populneus

Family: Malvaceae

Active Phytoconstituents: Lupeol, Gossypol, Quercetin, Beta-sitosterol^[4]

2. Taxonomy

Kingdom: Plantae

Division: Magnoliophyla

Class: Magnoliopsida

Order: Malvale

Family: Malvaceae

Genus: Thespesia

Species: T. populnea Linn

3. Vernacular names:

Sanskrit: Parisah, Kapitana, Phalisah, Gardabhandah.

Hindi: Paraspipal.

English: Portia tree, Umbrella tree.

Marathi: Parasa pimpala.

Bengali: Gajashundi, Paraasapipula.

Gujarati: Paraspipalo.

ENVIRONMENTAL CONDITIONS :

Common iCommonworld The species has been planted throughout the tropics, and it is naturalised in tropical climates throughout the world. It is a typical coastal species of South Africa and the Pacific Islands.In India: It is a common species in the coastal tracts of the Indian peninsula and in mangrove swamps. It is especially wild in South Kanara, Malabar, the deltas of Godavari and Mahanadi and in Cuttack. It is also found in the Sunderbans of West Bengal and in the Andamans. 

Uses  

These compounds encoPass several chemical classes such as alkaloids, flavonoids, carbohydrates phytosterols, tannins, Saponins, proteins and amino acids, terpenes, phenols and essential oils, exhibit significant  Pharmacological activity^[5]. The yellow juice of Thespesia fruits is employed in treating Hepatic diseases. A decoction from the bark is given internally for skin diseases and also as an antidote for poisoning. Various Parts of the Thespesia contain high tannin content, which has been shown to have anti-bacterial and anti-viral activity.The oil of bark and capsule is useful in Arthritis and Gonorrhea. The seed possesses purgative properties that promote free bowel Movement and provide relief from symptoMs of constipation. The plant is also effective in malaria treatment^[6]. Air-dried flowers of T. populnea contain kaempferol, β-sitosterol, Gossypetin, quercetin, and a mixture of kaempferol 3-glucoside, quercetin 3-glucoside, kaempferol 5-glucoside, rutin, kaempferol 3-rutinoside, and kaempferol 7-glucoside ^[7]. Dextro-rotatory gossypol has recently been isolated from flowers, Fruits, and bark. The gossypol Content in different Parts of the tree is a seed (3.14%), flower buds(3.37%), leaves (1.66%), roots (2.11%), and stem (1.43%). Presence of herbecetin and thespesin has been reported Leaf, flower and stem bark of T. populnea showed varying levels of protective action against CCl4-induced liver damage as evidenced from a significant reduction in the activities of serum marker enzymes for liver damage (alanine transaminase, aspartate transaminase, and alkaline phosphatase), and bilirubin levels when compared with CCl4-intoxicated control rats. The stem bark suspension showed maximum hepatoprotection compared with the leaf and flower. An ethanol extract of the stem bark was more active than n-hexane and water extracts; the hepatoprotective effect of this extract was almost comparable to that of silymarin (100 mg/kg), a reference herbal drug. Thus, the present study indicates that the ethanol extract of T. populnea bark is promising for further studies leading to hepatoprotective drug development ^[8].

Fig -1: Leaves of Thespesia populnea

The various chemical constituents isolated from the T. Populnea are Gossypol ^[9], 7 Hydroxy-2,3,5,6-tetrahydro-3,6,9 Trimethylnaphto [1,8-B, C] Pyran-4,8-Dione^[10]. Kaempferol, Quercetin ^[11], Kaempferol 3-glucoside, Quercetin 3-glucoside, Nonacosane, lupenone, myricyl alcohol, lupeol, β-sitosterol and β-sitosterol-β-D-glucoside  5, 8-dihydroxy-7-Methoxyflavone, 7-1ydroxyisoflavone and Thespone ^[12], Mansonones D, E and F Populneol, Thespesin^.[13].

Fig -2: Chemical Structure of Thespesia populnea

Stem bark contains Alkaloids, carbohydrates, Proteins,  tannins, Phenols, Flavonoids, Gums and Mucilage, Saponins And Terpenes^[14]. Thespesia populnea is reported to contain β-sitosterol-3-O-β-D-glucopyranoside-6’-O-stearate, β-sitosterol, daucosterol, kaempferol, 1-hentriacontanol, stearic acid, and botulin ^[15].

Leaves of T. populnea contain lupeol and β-sitosterol as the Major constituents^[16]plant extract exhibited a remarkable cholesterol-lowering property comparable to Simvastatin (a standard Drug).T. populnea bark possessed a powerful memory-enhancing activity in Mice. Since diminished cholinergic transmission and increased Cholesterol levels appear to be responsible for the development of Amyloid plaques and dementia in Alzheimer patients, Plant extract may prove to be a useful medicine on account of its multifarious Beneficial effects, such as memory-improving property, cholesterol-lowering, anti-cholinesterase and Anti-Inflammatory activity^[17]Terpenoid fraction from T. populnea leaves showed significant Antiulcer activity in experimentally induced Ulcer in the rat model by decreasing the Gastric Secretions and by enhancing Glycoprotein levels^[18]. The Analgesic activity was assessed using the acetic acid-induced writhing response and Formalin-induced paw licking time in the early and late phases of Mice. The higher doses of Plant extract (200 and 400 mg/kg, p.o.) were inhibiting Carrageenan (responsible for inflammatory reaction), Histamine and Serotonin-Induced Paw Oedema as well as Formaldehyde-Induced Arthritis successfully ^[19] Bark, Root and Fruits are stated to be used in Dysentery, Cholera, Haemorrhoids; the Mashed Bark is employed as a Politice or Hot fermentation for wounds and mainly responsible for Astringent Activity^[20]Seeds of T.populunea were successively extracted using Petroleum Ether (40–60ºC)and Ethanol. Unsaponifiable matter and fatty acids were separated from seed oil ^[21]Ethanolic extract was fractionated using CHCl3, Ethoxyacetate, n-Butanol and water as solvents. Acute arthritis was induced by sub-plantar injection of carrageenan into the left hind Paw of rats and the paw Volume was measured using Plethysmometer. Analgesic activity assessed by heat induced pains (tail immersion model) and antipyretic activity assessed using Brewer’s yeast-induced pyrexia Model. Oral administration of TPO And Plant extract at 200 and 400 mg/kg body weight and tested fractions at 200 mg/kg significantly reduced carrageenan induced paw enema and brewer’s Yeast-induced pyrexia ^[22] In tail immersion method also Extracts and fractions showed significant Analgesic activity. Amongst All fractions Ethoxyacetate showed most significant results. Unsaponifiable Matter showed significant anti-inflammatory and analgesic activity^[23]

INTRODUCTION TO TRANSDERMAL PATCHES:-

Transdermal patches are the adhesive patches In this method the medicament is directly released into the skin the systemic circulation .in 1981 the FDA The approved ever transdermal patch was the scopolamine patch, which is marketed under the brand name transdermal scop various transdermal patches are available they include clonidine and nitro-glycerine for cardiovascular ailments, fentanyl for chronic pain,  scopolamine for motion sickness, and nicotine for smoking cessation. These patches enable controlled and sustained pharmacological action, and they facilitate continuous drug delivery. These patches have major advantages for drugs with short biological half-lives.The major key parameters taken into consideration while characterising the adhesive property of patches are: tack, shear adhesion and peel adhesion.

LITERATURE REVIEW

1. Formulation and Evaluation of Transdermal Patch for Pain Management: Sakshi D. Ghodke, Vaishnavi M. Kalamkar, Swapnali R. Musmade, Devram K.Jori, Manoj L. Chaudhari (2025). Transdermal drug delivery has gained significant attention as a convenient and effective route for systemic drug administration. Unlike conventional oral formulations, transdermal systems bypass first-pass hepatic metabolism, thereby improving drug bioavailability and reducing the risk of gastrointestinal irritation and metabolic degradation. Herbal medicines, with their wide range of therapeutic properties, they also explored safer and more cost-effective alternatives to synthetic drugs. The herbal constituents in transdermal systems offer a promising strategy to overcome such challenges by ensuring sustained release, improved permeability, and enhanced therapeutic efficiency. The present study focused on the formulation and evaluation of herbal-based transdermal patches using rice and corn starch as natural polymeric bases. prepared patches were subjected to preliminary phytochemical screening to confirm the presence of active constituents responsible for therapeutic effects. The formulations were further evaluated for critical physicochemical parameters, including weight uniformity, thickness, and tensile strength, to ensure consistency and mechanical stability. Among the developed formulations, the optimised patch demonstrated satisfactory physical properties, effective drug release, and minimal skin irritation, suggesting its suitability for prolonged therapeutic application. The literature suggests that herbal-based transdermal patches represent a promising drug delivery system, combining the therapeutic benefits of phytoconstituents with the advantages of transdermal technology.

2. Phytochemical, Pharmacological and Phytopharmaceutics Aspects of Thespesia populnea (linn.) Soland. : A Review. Invent Impact: Ethnopharmacology. 1.  Chumbhale, Deshraj & Pawase, Amit & Chaudhari, S. & Upasani, Chandrashekhar. (2010). Thespesia populnea (Linn.) Soland., a member of the family Malvaceae, contains a diverse range of bioactive compounds, including terpenoids, lipids, glycosides, and flavonoids, which contribute to its wide spectrum of pharmacological activities.

Different parts of the plant—such as the roots, bark, leaves, flowers, and fruits—have been reported to exhibit distinct therapeutic properties. T. populnea in traditional medicine has been employed in the management of liver disorders, skin diseases, and inflammatory conditions. Its chemical constituents have been linked to free radical scavenging activity and protection against oxidative stress, thereby substantiating its potential application in the development of hepatoprotective and antioxidant formulations. The objective of this review is to present a detailed account of the phytochemical composition, pharmacological activities, and phytopharmaceutical applications of Thespesia populnea (Linn.) Soland. Special emphasis is placed on its therapeutic potential, particularly its role in traditional medicine and its prospects for development as a modern medicinal plant.

3. Memory-Enhancing Activity of Thespesia populnea in Rats: Mani, Vasudevan & Parle, Milind. (2007). Thespesia populnea (Soland ex Correa; Malvaceae) is a medicinal tree, traditionally recognised for its antibacterial, anti-inflammatory, antioxidant, purgative, and hepatoprotective properties. Ethanolic extract of T. Populnea bark (TPE) was administered orally at doses of 100, 200, and 400 mg/kg for seven consecutive days to young and aged rats. Memory performance was assessed using the elevated plus-maze and Hebb-Williams maze as exteroceptive models, while diazepam-, scopolamine-, and ageing-induced amnesia served as interoceptive models.TPE at 200 and 400 mg/kg significantly improved memory in both young and aged rats compared with controls. Furthermore, TPE effectively reversed memory deficits induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.).The observed cognitive benefits may be attributed to the extract’s cholesterol-lowering, anticholinesterase, anti-inflammatory, and antioxidant activities. These findings suggest that Thespesia populnea bark extract exhibits promising memory-enhancing effects and may serve as a potential natural therapeutic candidate for cognitive impairment. Further investigations, including mechanistic studies and clinical validation, are warranted to explore its application in the management of Alzheimer’s disease and related neurodegenerative disorders. The Present study was designed to assess the memory-enhancing effects of Thespesia populnea bark extract in rats employing validated behavioural models.

4. TRANSDERMAL PATCHES: A REVIEW OF A NEW DRUG DELIVERY SYSTEM APPROACH: Mahdiyyah, Ade & Diyah, Nuzul & Hendradi, Esti. (2022). Transdermal patch is a transdermal delivery system that can overcome problems in conventional drug administration, such as oral drug administration. Patches can provide controlled drug release and have advantages over oral administration, such as increasing drug bioavailability, avoiding adverse effects on the gastrointestinal (GI) tract, minimising patient variability, maintaining a constant drug in plasma, and minimising a stable therapeutic effect. The effectiveness of a patch is determined by the drug’s ability to release from the patch matrix and penetrate the stratum corneum. The methods used to make the patches are divided into single-layer, multi-layer, reservoir system, and matrix system patches. The basic components of a patch are a polymer matrix, membrane, drug, permeation enhancer, pressure-sensitive adhesives, backing film, release liner, and plasticiser This review focuses on patch analysis methods after manufacturing process, such as physical characteristics test, in vitro drug release test, in vitro skin permeation test, skin irritation test, and stability test, as well as some explanations related to the transdermal drug delivery system.

5. Dermal and Transdermal Drug Delivery Systems: Current and Future Prospects. Drug Delivery, Brown, M. B., Martin, G. P., Jones, S. A., & Akomeah, F. K. (2006). The protective function of human skin possesses physicochemical limitations to the types of substances that can traverse the barrier. For a drug to be delivered passively via the skin it needs to have adequate lipophilicity and also a molecular weight <500 Da. These requirements have limited the number of commercially available products based on transdermal or dermal delivery. Various strategies have emerged over recent years to optimise delivery, and these can be categorised into passive and active methods. The passive categorisation entails the optimisation of formulation or drug-carrying vehicle to increase skin permeabilityPassive methods, however, do not greatly improve the permeation of drugs with molecular weights >500 Da. In contrast, active methods that normally involve physical or mechanical methods of enhancing delivery are generally superior. Improved delivery has been shown for drugs of differing lipophilicity and molecular weight including proteins, peptides, and oligonucleotides using electrical methods (iontophoresis, electroporation), mechanical (abrasion, ablation, perforation), and other energy-related techniques such as ultrasound and needless injection.  This article provides a detailed review of the next generation of active delivery technologies.

6. A Review on Herbal Transdermal Patches D.S. Bhujbal, S. A. Kanase, V. V. Kunjir. Drug delivery technologies have become a major focus in the pharmaceutical industry to improve therapeutic efficiency, minimise adverse effects, and enhance patient compliance. Among these, transdermal patches stand out as a novel system, functioning as medicated adhesive patches that deliver drugs through the skin into systemic circulation. This route offers several advantages over conventional oral and injectable forms, such as non-invasiveness, controlled release, and improved patient comfort. Although synthetic drugs are widely used for treating complex diseases, their administration is often linked to side effects and safety concerns.

7.Thespesia populnea : AN UNDERUTILIZED COSMETOLOGICALLY POTENT PLANT Thespesia populnea (Linn.) Soland ex Correa, popularly known as the Indian Tulip Tree, is a traditionally valued plant that is gradually being recognised for its potential in cosmetology. The plant contains a rich array of phytochemicals such as flavonoids, tannins, saponins, and phenolic compounds, all of which are well known for their strong antioxidant, anti-inflammatory, and antimicrobial activities. These properties suggest that Thespesia populnea can play a vital role in protecting the skin from oxidative stress, delaying premature aging, promoting wound healing, and preventing microbial infections, thereby making it highly suitable for cosmetic formulations. Despite its diverse pharmacological and ethnomedicinal significance, the plant remains underexplored in terms of cosmetic applications, creating a gap between its traditional uses and modern scientific validation. With the current global shift toward herbal and sustainable beauty products, there is an urgent need for comprehensive research to evaluate, standardize, and formulate Thespesia populnea-based cosmetics. Bridging traditional knowledge with contemporary scientific studies could unlock its true potential as a natural, effective, and eco-friendly source of cosmetic ingredients, paving the way for its utilization in skincare, haircare, and other beauty-enhancing products.

OBJECTIVES:

1. To provide effective relief from inflammation and severe pain, thereby helping reduce the risk and progression of various associated diseases.

2. To reduce dosing frequency and enhance patient adherence to therapy.
3. To facilitate the management of diabetes through the regulation and maintenance of blood glucose levels.
4. To enable the delivery of drugs that are poorly absorbed or unstable in the gastrointestinal environment.

FACTORS AFFECTING TRANSDERMAL PATCHES:

• pH
• Temperature
• Molecular weight
• Partition coefficient
• Biotransformation of a drug in the skin
• Cutaneous microcirculation
• Hydration
• Age
• Gender
• Body site
• Sun exposure
• Skin condition

MECHANISM OF ACTION:

Transdermal permeation of a drug moiety involves the following steps:

1. Sorption by stratum corneum

2. Permeation of the drug through viable epidermis

3. Uptake of the drug moiety by the capillary network in the dermal papillary layer.

4. The drug must possess some physicochemical properties to reach the target site systemically through the stratum corneum.

The rate of permeation of a drug through the skin is governed by the following equation:

dQ/dT = ps(Cd -Cr)

Where, Cd concentration of penetrant in the donor phase (on the surface of skin);       

 Cr- concentration of penetrant in the receptor phase (body)

 Psis the overall

permeability coefficient of the skin which is defined as  

Ps=ks Dss/hs

Where, K = Partition coefficient of the penetrant

Dss Apparent diffusivity of penetrant

 hs Thickness of skin

ROUTES OF DRUG PENETRATION THROUGH SKIN :

Drugs penetrate through the skin through various pathways, depending on the formulation and chemical properties of the drug

Fig. 5: Route for penetration of the drug by transdermal drug delivery system

MATERIALS USED IN FORMULATION OF TRANSDERMAL PATCHES:

1.POLYMERS:

Mainly Regulates or Controls the DRUG from Medicated Patch.

A.NATURAL:

Starch, Gelatin,  Waxes, Gums, Natural Rubber.

B.SYNTHETIC:

Polyvinyl Alcohol ,Polymethyl Actylate ,Poly Urea,  Chloride, Polyethylene, Polyvinyl Pyrrolidone, Polypropylene.

2.API/DRUG:

For the incorporation of Drug into the Transdermal Drug the Necessary Physicochemical Properties are:

• Should have Molecular Weight less than 1000 Daltons.
• Low Melting Point.
• Should be Potent [Effective at Mininmum Concentration],Shorter Half Life, Non-Irritative.
• Have both Affinity for both Hydrophilic and Lipophilic Phases.

3.PERMEATION ENHANCERS:

Agents or Chemical Substances that facilitate the permeability of skin by modifying the skin as a barrier to the flux of a desired penetrant that includes:

A. SOLVENTS:

Increases the penetration by Fluidizing the lipid or oily substances present at the surface of the Skin.

B.Miscellaneous chemicals:

These include urea, a hydrating and keratolytic agent; N, N-dimethyl-m-toluamide; calcium thioglycolate; anticholinergic Agents.some potential permeation enhancers have recently been described but the available data on their effectiveness sparse. These include Eucalyptol, di-o-methyl-ß-cyclodextrin and soyabean casein ^[24]

GENERAL METHOD OF FORMULATION OF TRANSDERMAL PATCHES:

1.SOLVENT CASTING METHOD:

It is a common method to formulate patches. The drug is mixed into a solution containing  a Polymer, a plasticizer, and other ingredients ^[25].This liquid is then poured onto a flat surface, like a piece of glass or a Teflon sheet. After pouring, the liquid evaporates under controlled conditions, leaving behind a thin, flexible film. Once it’s dry, the film is cut to the required size. A Backing layer and liner were considered to help for an  application ^[26]

2.HOT MELT-EXTRUSION METHOD:

This method doesn’t use any liquid solvents and is good for drugs and polymers that can resists a higher temperature. The drug is mixed with polymers and melted together in a Hot-Melt Extruder. The hot mix is then made into a thin film, cooled down, and cut into patches ^[27].

3.DIRECT COMPRESSION METHOD:

This method involves mixing the drug with dry ingredients like polymers, fillers, and Binders. This dry mix is then pressed by a machine into a thin sheet or film. The sheet is then given a backing and sticky layers to make a complete patch. This method is fast, cost effective, and doesn’t require heat or liquids, which is useful for drugs that are susceptible to  heat or moisture.

4. MEMBRANE CONTROLLED RESERVOIR SYSTEM:

The drug is turned  into a gel or liquid and stored in a reservoir. The reservoir is placed between a backing layer and a membrane that controls the release of the drug. The reservoir is sealed to prevent leaks. This system ensures a steady release of the drug over time, making it suitable for long-term treatments that need stable blood levels, like hormone or pain relief .

5.MATRIX DISPERSION METHOD:

In this method, the drug is directly mixed with a polymer to form a solid or semi-solid structure called a matrix. This matrix is spread onto a Backing layer and allowed to dry. Once the film forms, it’s covered with an adhesive and liner. the drug is evenly spread in the matrix, and when the patch is used, it  causes the prolong release of drug and slowly passes through the skin. This method doesn’t require any special reservoir or membrane.

6.ADHESIVE DISPERSION METHOD:

In this approach, the drug is mixed into a Pressure-sensitive adhesive that serves as both the drug holder and the sticky part that attaches to the skin. This mixture is spread on a backing layer and dried to form a patch. It is a popular method due to its simplicity and effectiveness in ensuring close contact with the skin for better Absorption. It tends to be used for drugs that are needed in low doses.

7.MICRO RESERVOIR SYSTEM:

This hybrid system combines the benefits of Reservoir and Matrix patches. It creates tiny doplets of the drug within a gel, embedded into a polymer matrix. This allows for precise control of drug release over a longer period. The droplets are stable and evenly spread across the Patch, offering both flexibility and controlled release. This system is suitable for drugs that need extended release and steady blood levels.

8.MULTILAMINATE FILM METHOD:

In this technique, multiple film layers are made separately, with each layer doing a different job, like a drug layer, a sticky layer, or a barrier layer. These layers are then joined together to form One patch with controlled drug release. The Multilayer design allows for adjusting drug release, protecting the drug from outside exposure, and improving the patch’s strength and flexibility.

9.ELECTRO-SPRAYING METHOD:

This method is used to create super-thin films or particles. The drug-polymer mixture is charged and sprayed in a high-voltage electric field onto a surface to form a thin film. Electro-spraying forms small structures and increases the surface, helping the drug release better. Although it’s more complex, it’s helpful for Modern Patches that need to act quickly or enhance absorption ^[28].

10. SUPERCRITICAL FLUID METHOD:

This innovative approach uses supercritical fluids like supercritical CO? to create films that go on the skin. These fluids work as solvents under High pressure and temperature, dissolving the Drug and polymers. Then, when the pressure lowers, the fluid disappears, filled with the drug. This method is environmentally friendly, doesn’t leave residues  behind, and achieves uniform, stable drug films, making it suitable for sensitive drugs and advanced skin patch systems ^[29]

Table 1: Ingredients for Formulation