INTRODUCTION:

Transdermal Patch:

The transdermal delivery system is considered one of the most effective approaches in modern drug delivery. Compared with conventional routes such as oral and injectable administration, transdermal drug delivery offers several advantages. In this system, the drug is incorporated into a patch and absorbed through the skin, providing a convenient and painless method of administration. It also helps to prevent gastrointestinal side effects, such as peptic ulcer disease, and bypasses hepatic first-pass metabolism. Although transdermal drug delivery has existed since the 1800s, it has evolved significantly beyond simple adhesive patches. With recent technological advancements and improved formulations that minimize skin irritation while targeting the site of action, the transdermal route has become an increasingly accepted and widely used method of drug administration. [Jamaandi et.al]¹

The oral route is generally considered the most convenient and preferred method of drug administration; however, it has several limitations, including hepatic first-pass metabolism, low bioavailability, and the tendency to cause rapid fluctuations in blood drug levels, which often necessitate frequent dosing. To address these challenges, the development of novel drug delivery systems is essential. Transdermal drug delivery systems offer a controlled and predictable release of drugs, providing prolonged therapeutic activity over an extended period. [Bagyalakshmi and Vmshikrishna et.al] ²

Transdermal drug delivery systems (TDDS) containing trazodone hydrochloride were formulated and evaluated using ex-vivo experiments. Information in the literature regarding the transdermal administration of trazodone is limited, with only one reported formulation consisting of a topical film made from a blend of Eudragit RL 100 and RS 100 combined with various penetration enhancers. Drug-in-adhesive (DIA) patches represent the simplest type of transdermal system, where the drug is either dissolved or dispersed directly within the pressure-sensitive adhesive (PSA). The PSA plays a crucial role in maintaining intimate contact between the patch and the skin for the intended duration of use, as well as regulating the drug release rate. Consequently, selecting an appropriate PSA is a critical step in TDDS development.

which significantly restricts trazodone solubility. Therefore, the study focused on acrylic adhesives. The first acrylic adhesive evaluated was Plastoid, an aqueous-based system composed of Eudragit E 100, lauric acid, and adipic acid, which was expected to facilitate the solubilization of trazodone hydrochloride. Two transdermal patches containing different drug loadings (Plastoid T7 and Plastoid T14) were formulated, characterized, and subjected to ex-vivo permeation studies.

Figure.1: Transdermal drug delivery.

Advantages and Disadvantages of Transdermal Patch.

Advantages:

1. Prevent liver and GI first pass Metabolism

2. Offer reliable control absorption.

3. Lessens adverse effects

4. Minimize contact with harmful Metabolites.

5. Increased patient compliance as a result of the removal of multiple dosage.

6. Boost treatment effectiveness.

7. Simple to apply and take off.

8. Painless and non-intrusive.

9. Self-management. [Prausnitz M et.al]³

Disadvantages:

1. Prices are high.

2. Ionic medicines cannot be delivered by TDDS.

3. High drug levels in the blood or plasma Cannot be achieved with TDDS.

4. Drugs with large molecular sizes cannot Be developed using TDDS.

5. Pulsatile medication delivery is not Possible with TDDS

6. If a medicine or formulation irritates the Skin, TDDS cannot occur. [Patel D, Chaudhary SA et.al]⁴

Types of Transdermal Patch:

A. Single Layer Drug in Adhesive:

In this system, the drug is incorporated within the adhesive layer. This adhesive layer performs a dual function: it secures the different components of the patch and ensures adhesion of the entire system to the skin, while simultaneously controlling the release of the drug. The adhesive layer is enclosed between a temporary protective liner and an external backing layer.

B. Multi-Layer Drug in Adhesive:

The multilayer drug-in-adhesive patch is comparable to the single-layer system in that the adhesive components function not only to secure the patch but also to mediate drug release. In this design, one adhesive layer provides immediate drug release, while the second layer enables controlled release from the drug reservoir. Unlike the single-layer configuration, the multilayer system incorporates an additional drug-in-adhesive layer, which is typically, though not invariably, separated by a membrane. Similar to other transdermal systems, this patch consists of a removable protective liner and a permanent backing layer.

C. Reservoir:

In contrast to single-layer and multilayer drug-in-adhesive systems, reservoir-type transdermal systems incorporate a distinct drug-containing layer. This layer consists of a liquid reservoir that holds the drug in the form of a solution or suspension and is separated from the skin by an adhesive layer. The entire system is supported by an impermeable backing layer. A defining characteristic of reservoir transdermal systems is that they deliver the drug at a controlled, zero-order release rate.

D. Matrix:

The matrix transdermal system consists of a drug-containing layer in which the active pharmaceutical ingredient is uniformly dispersed within a semisolid polymeric matrix, either as a solution or suspension. In this design, the adhesive layer partially surrounds and overlaps the drug matrix. This type of transdermal patch is also commonly referred to as a monolithic system.

Method of Preparation of Transdermal Patch:

Common materials include ethanol, lauric acid, Adipic acid Eudragit, glycerine and water.

Preparation for Transdermal Patch: Transdermal Patch are prepared form aqueous material, polymer and water solvent by using different method and are,

1. Solvent Evaporation method.

2. Solvent casting method.

3. Other methods.

· Mercury substrate method

· Asymmetric TPX membrane method

· Free film method

· Proliposome based method

1.Solvent Evaporation Method: Eudragit L100 and Eudragit S100 were weighed in the required amounts as specified in Table 1. Approximately 20mL of a dichloromethane–methanol solvent mixture (1:1) was added, and the mixture was shaken to prevent lump formation before being allowed to stand for polymer swelling. After the polymers were completely dissolved in the solvent system, the specified quantity of dibutyl phthalate was incorporated, followed by the addition of glycerin, and the mixture was vortexes thoroughly. A weighed amount of Trazodone hydrochloride was then added to the polymer solution and mixed uniformly.

The solution was allowed to stand for a short period to remove any entrapped air and was subsequently poured into a previously cleaned Petri dish containing aluminum foil–wrapped rings. The dish was left undisturbed to allow solvent evaporation, with the evaporation rate controlled by placing an inverted glass funnel over the Petri dish. Transdermal patches corresponding to the compositions were successfully prepared. The finalized patches were stored in aluminum pouches and kept in a desiccator for further evaluation. [SirishaV.N. L, Sheth Nirav S et.al]^5,6

2. Solvent Casting method: Transdermal patches were formulated using the solvent casting technique. Precisely weighed quantities of polymers in various ratios were dissolved in an ethanol–water mixture (1:1) and set aside until a clear solution was

obtained. The drug was then dissolved separately and incorporated into the polymer solution with continuous mixing to achieve uniformity.

Glycerine, at 20% v/v of the total polymer composition, along with varying concentrations of the permeation enhancer DMSO, was added to the mixture and stirred thoroughly. Subsequently, 10mL of the prepared solution was poured onto a Petri dish, and a suitably sized inverted funnel was placed over it. The solvent was allowed to evaporate at room temperature for 24hours to form dry patches. After drying, the patches were carefully removed, wrapped in aluminum foil, sealed in self-locking covers, and stored in a desiccator until further evaluation. [Yong Wang et.al]⁷

3. Other Methods:

· Mercury substrate method: In this approach, the drug and plasticizer are first dissolved in a polymer solution. The resulting mixture is shaken for about 10–15 minutes to obtain a homogeneous dispersion, which is then poured onto a leveled mercury surface. An inverted funnel is placed over the solution afterward to minimize solvent evaporation.

· Asymmetric TPX membrane method: They are prepared using the dry/wet phase inversion technique. In this method, TPX is dissolved in cyclohexane along with non-solvent additives to form a polymer solution. After maintaining the solution at 40°C for 24hours, it is cast onto a glass plate at a predetermined thickness using a casting blade. Once the solvent is allowed to evaporate at 50 °C for 30 seconds, the glass plate is immediately immersed in a coagulation bath maintained at 25°C. After 10 minutes of immersion, the formed film is removed and then air-dried in a convection oven at 50°C for 12hours

· Free Film Method: Casting the polymer solution onto a mercury surface produces a free-standing cellulose acetate film. A 2% w/w polymer solution is prepared using chloroform as the solvent, with plasticizers incorporated at 40% w/w relative to the polymer. Five milliliters of this solution are poured into a glass ring placed on a shallow layer of mercury in a glass Petri dish. An inverted funnel is positioned over the dish to control the rate of solvent evaporation. Once the solvent has completely evaporated, the formed film becomes visible on the mercury surface. The dried film is then carefully removed and stored in a desiccator between sheets of wax paper until further use. Films of varying thickness can be obtained by adjusting the volume of the polymer solution.

· Proliposome Based Method: Proliposome are prepared using the film deposition method combined with a carrier-based technique. Lecithin at a ratio of 0.1:2.0 with respect to the reference drug may be used as an optimized formulation. To prepare the proliposomes, 5 mg of mannitol powder is placed in a 100mL round-bottom flask preheated to 60–70°C. The flask is rotated at 80–90rpm while the mannitol is vacuum-dried for 30 minutes. After drying, the temperature of the water bath is adjusted to 20–3°C.

The drug and lecithin are dissolved in an appropriate organic solvent mixture. A 0.5mL portion of this solution is added to the round-bottom flask maintained at 37°C. Once the solvent has completely evaporated, an additional 0.5mL of the solution is introduced. After loading the proliposomes with the drug, they are placed in a desiccator for short-term storage and then passed through a 100-mesh sieve. Upon completion of the loading process, the flask containing the proliposomes is connected to a lyophilizer. The resulting powder is collected and stored in a glass container under frozen conditions until characterization.

Evaluation of Transdermal Patch:

1. Folding endurance: A specific section of the strip measuring 2 × 2cm was cut evenly and repeatedly folded at the same point until it failed. Folding endurance was calculated as the number of folds required to cause either breakage of the film or the appearance of visible cracks. [Keleb E, Sharma RK, Bangale GS et.al]^8,9

2. Tensile Strength: The tensile strength of the patch was evaluated using a tensiometer (Erection and Instrumentation, Ahmedabad) equipped with two load cell grips. The lower grip was kept stationary, while the upper grip was movable. Film strips of 2 × 2cm were positioned between the grips, and a gradually increasing force was applied until the film ruptured. The tensile strength was then calculated based on the dial reading expressed in kilograms. [Shivaraj A et.al]¹⁰

3. Thickness: The thickness of the transdermal patches was measured at three different points using a digital micrometer screw gauge, and the mean thickness along with the standard deviation was determined. [Pandit V, et.al]¹¹

4. Percentage moisture content: The prepared transdermal films were weighed individually and placed in a desiccator containing fused calcium chloride at room temperature for 24 hours. After this period, the films were weighed again, and the percentage moisture content was calculated using the following equation.

Final weight − Inital weight x100

Percentage = --------------------------------------------------

Moisture Uptake Inital weight

5. Swelling Study: The prepared transdermal patches were individually weighed (W1) and then incubated in 2% agar gel plates at 37± 0.5°C. At predetermined intervals of 15 minutes for a total duration of 1 hour, the patches were removed from the Petri dishes. Surface moisture was gently blotted off using filter paper, after which the swollen patches following formula. [Nishad KM, Pandey S et.al]¹²

W2 – W1

Swelling index = ------------------------ x 100

6. Drug Content: A 2 × 2cm transdermal patch was dissolved in 100mL of methanol and continuously shaken for 24hours. The resulting solution was then ultrasonicated for 15 minutes. After filtration, the drug content was determined by spectrophotometric analysis at 292nm. [Garala KC et.al]¹³

Application of Transdermal Patch:

· Patches can deliver the drug at a constant, steady rate over a prolonged period (e.g., 24 hours), which helps to avoid the fluctuating plasma levels associated with oral doses.

· Maintaining stable drug levels and avoiding high peaks in concentration could potentially reduce common side effects like lightheadedness and postural hypotension.

· A simple, once daily or less frequent patch application is more convenient than multiple daily pills, which can improve patient adherence to treatment.

· This method is beneficial for patients who have difficulty swallowing pills, are unconscious, or are experiencing vomiting. This has been particularly explored and applied in veterinary settings for cats with anxiety during transport and vet visits, where oral pilling is difficult for owners.

· The first-pass metabolism in the liver, which affects orally administered drugs.

CONCLUSION:

Transdermal permeation of trazodone has received limited investigation to date. The findings from the initial phase of this study help to address this knowledge gap and provide valuable insights into the development and optimization of transdermal delivery systems. demonstrated that the influence of vehicle PH on trazodone skin permeation is complex, as pH affects both drug solubility and its partitioning behavior. Additionally, the inclusion of fatty acids in the formulation significantly enhanced trazodone permeation, yielding an enhancement factor of approximately 100.

Transdermal delivery of trazodone is a promising strategy to improve bioavailability, maintain steady therapeutic levels, and enhance patient compliance. Advances in polymer matrices, nan carriers, and microneedle technology make it feasible, though challenges like skin permeability and irritation require careful formulation optimization.

Transdermal drug delivery of trazodone presents a promising alternative to oral administration, potentially improving patient compliance and minimizing first-pass metabolism. Formulation studies indicate that suitable transdermal systems can achieve sustained drug release, maintain therapeutic plasma levels, and reduce gastrointestinal side effects commonly associated with oral trazodone. However, challenges such as drug permeability through the skin, stability, and optimizing the formulation for consistent absorption remain. Overall, transdermal delivery could enhance the safety and efficacy profile of trazodone, but further in vivo studies and clinical trials are necessary to fully establish its therapeutic viability.

REFRENCES:

1. Jamaandi VG, Mulla JS, Vinay BL. Formulation and Evaluation of matrix- type transdermal patches of a Model antihypertensive drug. Asian Journal of Pharmaceutics. 2009; 8(1): 59-65.

2. Bagyalakshmi J, Vmshikrishna RP. Preparation, Optimization and in vitro & vivo evaluation of Membrane-moderated transdermal delivery of Ampicillin sodium. AAPS Pharm. Sci. Tech. 2008; 8(1): 50-55.

3. Prausnitz, M. R., Mitragotri, S., and Langer, R. Status and Future potential of transdermal drug Delivery. Nat. Rev. Drug Discov. 2004; 3: 115–124. Doi:10.1038/nrd1304.

4. Patel D, Chaudhary SA, Parmar B, Bhura N. Transdermal drug delivery System: a review. The Pharm Innovation. 2012; 1(4): 66-75.

5. SirishaV.N. L, Kirankumar P: Formulation and Evaluation of transdermal patches of propra-Nolol Hydrochloride, IOSR Journal of Pharmacy: 2012; 2(5): 31-37.

6. Sheth Nirav S. mistryRajan: Journal of Applied Pharmaceutical Science. 2011; 1(3): 96-101.

7. Yong Wang, Xiao-Ping Zhao and Jian-Wei Ruan. Transdermal Drug Delivery System of Aceclofenac for Rheumatoid Arthritis and the Effect of Permeation Enhancers: In vitro and in vivo Characterization. International Journal of Pharmacology. 2015; 11(5): 456-462

8. Keleb E, Sharma RK, Mosa EB, Aljahwi A AZ. Transdermal drug delivery system design and evaluation. Int J Adv Pharm Sci. 2010; 1: 201–11.

9. Bangale GS, Rathin Raj BS, Rajesh KS, Shinde GV, Umalkar DG, Rajveer CH, et al. Design and evaluation of transdermal films of Atenolol. J Chem Pharm Res. 2010; 2: 59604.

10. Shivaraj A, Selvam RP, Mani TT, Sivakumar T. Design and Evaluation of transdermal drug delivery of ketotifen fumarate. Int J Pharm Biomed Res. 2010; 1: 42–7.

11. Pandit V, Khanum A, Bhaskaran S, Banu V. Formulation and Evaluation of transdermal films for the treatment of overactive Bladder. Int J Pharm Tech Res. 2009; 1:799–804.

12. Nishad KM, Arul B, Rajasekaran S. Design and comparative Evaluation of clarithromycin gastric bioadhesive tablets by ex vivo and vivo methods. Asian J Pharm Clin Res. 2018; 11: 248–56.

13. Pandey S, Shah RR, Gupta A, Arul B. Design and evaluation of Buccoadhesive controlled release formulations of prochlorperazine Maleate. Int J Pharm Sci. 2016; 8: 3759.

14. Garala KC, Shinde AJ, Shah PH. Formulation and in vitro Characterization of monolithic matrix transdermal systems Using HPMC/Eudragit S 100 polymer blends. Int J Pharm Sci. 2009; 1: 108–20.

Received on 14.05.2026 Revised on 05.06.2026

Accepted on 24.06.2026 Published on 07.07.2026

Available online from July 10, 2026

Res. J. Pharma. Dosage Forms and Tech.2026; 18(3):247-251.

DOI: 10.52711/0975-4377.2026.00035

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 International License. Creative Commons License.