We use cookies to make sure that our website works properly, as well as some ‘optional’ cookies to personalise content and advertising, provide social media features and analyse how people use our site. Further information can be found in our Cookies policy
Ondansetron hydrochloride (HCl), a 5-HT3 receptor antagonist, is widely utilized to prevent nausea and vomiting, particularly in chemotherapy patients. Despite its therapeutic efficacy, its brief biological half-life and first-pass metabolism limit its bioavailability through conventional routes. Transdermal drug delivery offers a controlled and sustained release profile, thereby improving adherence to therapy. This review explores diverse strategies for the development and analysis of Ondansetron HCl transdermal patches, with a focus on polymer selection, film-forming techniques, and physicochemical property evaluation.
Keywords
Transdermal patch, TDDS
Introduction
Oral and injectable forms of Ondansetron HCl, though effective, often necessitate multiple dosing and are associated with gastrointestinal or parenteral drawbacks. Transdermal systems can bypass hepatic first-pass metabolism and offer steady plasma drug levels. The development of patches involves multiple formulation variables, including drug-polymer interactions, release enhancers, and matrix design.
Transdermal Patch
Transdermal patches represent a sophisticated drug delivery system that administers drug through the skin, ensuring controlled and sustained release into systemic circulation. They are part of the broader category known as Transdermal Drug Delivery Systems (TDDS).
Key features include:
Non-invasive: Avoids the gastrointestinal tract and first-pass hepatic metabolism.
Controlled Release: Provides sustained or controlled drug delivery over hours or days.
Improved patient compliance: especially advantageous for chronic conditions.
Basic components of a transdermal patch are:
Backing Layer – Protects the patch from external environment.
Drug Reservoir or Matrix – Contains an active ingredient and excipients.
Rate-Controlling Membrane (in some designs) – Controls the rate of drug diffusion.
Adhesive Layer – Ensures attachment to skin.
Release Liner – Removed before application.
Advantages:
Maintains constant plasma drug levels
Bypasses gastrointestinal degradation
Reduces dosing frequency
Minimizes side effects
Preparation methods:
Solvent Casting Method
Drug and polymer are together dissolved in a volatile solvent, cast onto a flat surface, and air-dried to form a thin film used as the transdermal patch.
Hot Melt Extrusion
Drug and polymers are mixed and melted at high temperatures, then extruded through a die to form thin films without using solvents, reducing residual solvent concerns.
Microneedle-Assisted Coating
Microneedles are coated with a drug-loaded polymer solution or hydrogel that dissolves upon skin insertion, enhancing permeation through the stratum corneum.
Electrospinning
Applying a high-voltage electric field to a polymer-drug solution produces nanofibers, which are deposited as a film resembling a patch, offering improved drug release characteristics
Membrane Permeation Method
The drug reservoir is sandwiched between an impermeable backing layer and a rate-controlling membrane, forming a patch that facilitates drug delivery through passive diffusion mechanisms
Drug Diffusion Through Skin Membrane: Step-by-Step
Drug Release from Transdermal Patch
When the patch comes in contact with the dermal layer:
The drug gets released from the matrix or reservoir in a controlled manner.
This release can be governed by diffusion, osmosis, or controlled membranes.
Penetration Through the Stratum Corneum (SC)
This is the outermost layer of skin, made of dead, keratinized cells embedded in lipids.
It's the main barrier to drug permeation.
Drug molecules pass through via:
Intercellular pathway (between cells through lipid matrix)
Transcellular pathway (through cells – less common)
Appendageal route (through sweat glands or hair follicles – limited but faster)
Diffusion into Viable Epidermis
Below the SC lies the viable epidermis, a more hydrated environment.
Drug molecules diffuse passively due to a concentration gradient.
No blood vessels here, so drug continues moving deeper.
Passage Through Dermis
The drug reaches the dermis, which contains:
Capillaries
Lymphatic vessels
Nerve endings
Here, the drug is taken up into systemic circulation via capillaries.
Key Influencing Factors in Drug movement across membrane
Drug characteristics: Lipophilicity, molecular weight, and ionization
Skin condition: Hydration, integrity, and temperature
Enhancers: Use of ethanol, surfactants, microneedles, or electric fields (iontophoresis)
Figure 1: Mechanism of drug absorption through different strata of Skin
Table 1: Comparison of Oral vs. Transdermal Ondansetron
Route
Bioavailability
Duration
Patient Compliance
First-pass Effect
Oral
~60%
Short
Moderate
Present
Transdermal
~85–90%
Long
High
Avoided
Caption: Relative Benefits of Transdermal Administration of Ondansetron HCl.
Formulation Techniques
The majority of transdermal patches are formulated using the solvent casting technique, wherein the drug is incorporated into a volatile solvent containing a polymeric film-forming agent. Polymers such as hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), and Eudragit are commonly used. Plasticizers like polyethylene glycol (PEG 400) and propylene glycol are included to enhance flexibility and modulate drug release kinetics (Vemula et al.)
Table 2: Common Polymers Used in Transdermal Patches
Polymer
Function
Properties
HPMC
Film former
Hydrophilic, biocompatible
PVP
Enhancer & stabilizer
Good solubility
Eudragit RL100
Matrix former
Sustained release
Ethyl cellulose
Barrier modifier
Water-insoluble, durable
Figure 2: Solvent Casting Method of Patch Preparation
Certain studies have investigated combination therapy by integrating dexamethasone with Ondansetron to enhance antiemetic efficacy through synergistic action. (Sahu et al.).
Evaluation Parameters
Physicochemical Properties:
Evaluations such as uniformity in weight, thickness, drug content, and surface pH confirm uniformity between batches and assess the formulation’s appropriateness for skin application.
Table 3: Evaluation Parameters and Typical Ranges
Test Parameter
Method Used
Typical Result (Range)
Thickness
Vernier caliper
0.20 – 0.30 mm
Weight variation
Digital balance
±5% variation
Folding endurance
Manual folding
>200 folds
Drug content
UV-spectroscopy
95% – 105%
Mechanical Properties:
Tests like folding endurance, tensile strength, and moisture absorption assess the physical integrity and stability of the patches.
In Vitro Permeation Studies:
Drug release and permeation profiles are studied using Franz diffusion cells and synthetic or biological membranes, most studies report sustained release throughout a 24-hour period, with formulations showing zero-order or Higuchi kinetics (Patch et al.).
Figure 3: Franz Diffusion Cell Setup
Table 4: Parameters and Thresholds for In Vitro Testing
Test Parameter
Method Used
Typical Result (Range)
In vitro release (24 hr)
Franz cell + buffer
~85% (Sustained Release)
Skin Irritation and Ex Vivo Studies:
Patches undergo dermatological testing, often on albino rats or human cadaver skin, to assess irritation and permeability. Results confirm minimal dermal irritation potential and satisfactory flux rates (Swain et al.).
Challenges and Innovations
While transdermal delivery of Ondansetron HCl is promising, challenges remain—especially in achieving the desired drug flux without irritancy. Recent innovations, such as graphene oxide-based patches for photothermal-triggered delivery, present futuristic directions (Teodorescu et al.).
CONCLUSION
Transdermal patches of Ondansetron HCl represent a viable alternative to oral and injectable forms, especially for chronic and outpatient settings. Advances in polymer science and permeation enhancers have greatly improved the feasibility and safety of these systems. However, further clinical studies are needed to establish efficacy in larger patient populations.
REFERENCE
Vyas S.P., Khar R.K., Controlled Drug Delivery-Concepts and Advances, 1 st Edition, Vallabh Prakashan, 2002, 411- 445
Jain NK (2001) Controlled and novel drug delivery. (1st Edn.) CBS Publisher and Distributors, New Delhi, India 2001: 100-129.
Dhiman S, Thakur G, and Rehni A: Transdermal patches: A recent approach to new drug delivery system. International Journal of Pharmacy and Pharmaceutical Sciences., 2011; 3: 26-34.
Morrow DIJ, McCarron PA, Woolfson AD, and Donnelly RF: Innovative strategies for enhancing topical and transdermal drug delivery. The Open Drug Delivery Journal., 2007; 1: 36-59.
Tortara GJ, Bryan H. Derrickson (2011) Principles of Anatomy and Physiology, (9th Edn.) 140-94.
David SRN, Rajabalaya R, Zhia ES. Development and in vitro evaluation of selfadhesive matrix-type transdermal delivery system of ondansetron hydrochloride. Trop J Pharm Res. 2015;14(2):211–8.
Bhardwaj S, Bhatia S, Singh S. Transdermal Delivery of Ondansetron Hydrochloride in the management of Hyperemesis Gravidarum. Int J Pharma Sci Res. 2020;11(8):206–14.
Misra, A.N. 1997. Controlled and Novel Drug Delivery. In: Jain NK, editors. Transdermal Drug Delivery. New Delhi, India: CBS Publisher and Distributor, pp. 100-101.
Rajabalaya, R., Chen, D.S., David, S.R.N. 2013. Development of transdermal ondansetron hydrochloride for the treatment of chemotherapy-Induced nausea and vomiting. Trop. J. Pharm. Res. 12, 279-285.
Mohd, F. Bontha, L.S., Bontha, V.K., Vemula S.K. 2017. Formulation and evaluation of transdermal films of ondansetron hydrochloride. MOJ Bioequiv Availab. 3, 86-92.
Makoto, S.; Sierra, C.; Naoko, N.; Marina, E.; Alan, Y.; Ruxandra-Ioana, A.; Evelina, P.; Paolo, C.; Ken, Y.; Jason, H.; & Kazuyoshi, A. (2025). Effect of Ondansetron and Metoclopramide on postoperative nausea and vomiting in children undergoing tonsillectomy with or without adenoidectomy: a systematic review with meta- analysis. Journal of Anaesthesia, Vol. 39, pages 345-354, print ISSN 0913-8668 (e-ISSN) is 1438-8359
Chilkoti, Geetanjali T; Nandanan, Janaki; Saxena, Ashok Kumar; Seth, Varun; Kaur, Navneet1; Maurya, Prakriti. Low dose ondansteron with dexamethasone for prophylaxis of postoperative nausea and vomiting following laparoscopic cholecystectomy- A randomized double-blind study. Journal of Anaesthesiology Clinical Pharmacology, Vol. 41, No.1, (Jan-Mar 2025), pp. 84-89, Print ISSN: 0970-9185 Online ISSN: 2231-2730
Sunita N. Vaidya, “Innovations in Topical Drug Delivery: Recent Developments in Transdermal Formulations, Gels, and Patches as Topical Medication Delivery Methods”, AJP, vol. 18, no. 04, Dec. 2024. Print ISSN: 0973-8398, Electronic ISSN: 1998-409X
Patel M, Patel A, Desai J, Patel S. Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations. AAPS Pharm SciTech. 2024 Feb 27;25(3):46. doi: 10.1208/s12249-024-02763-4. PMID: 38413430. ISSN (Print): 1530-9932, ISSN (Online): 1530-9932
Suksaeree, J., Maneewattanapinyo, P., Panrat, K. et al. Solvent?Cast Polymeric Films from Pectin and Eudragit® NE 30D for Transdermal Drug Delivery Systems. J Polym Environ 29, 3174–3184 (2021). https://doi.org/10.1007/s10924-021-02108-3, ISSN (Print): 1566-2543, ISSN (Online): 1572-8919
Kailash Sahu, Saman Pathan, Kapil Khatri, Neeraj Upmanyu and Satish Shilpi Development, Characterization, In Vitro and Ex Vivo Evaluation of Antiemetic Transdermal Patches of Ondansetron Hydrochloride and Dexamethasone GSC Biological and Pharmaceutical Sciences, 2021, 14(03), 067-078.
Bharathi, D., Reddy, C. S., Babu, G., & Shirisha, Y. (2017). Formulation and Evaluation of Ondansetron HCl Transdermal Patch. World Journal of Pharmaceutical Research, 6(16), 417–426.
Mohd, F., Bontha, L. S., Bontha, V. K., & Vemula, S. K. (2017). Formulation and evaluation of transdermal films of ondansetron hydrochloride. MOJ Bioequivalence & Bioavailability, 3(4), 00039.
Teodorescu, F., Queniat, G., Foulon, C., & Szunerits, S. (2017). Transdermal skin patch based on reduced graphene oxide: A new approach for photothermal triggered permeation of ondansetron across porcine skin. Journal of Controlled Release, 245, 137–146.
David, S. R. N., Rajabalaya, R., & Zhia, E. S. (2015). Development and in vitro evaluation of self-adhesive matrix-type transdermal delivery system of ondansetron hydrochloride. Tropical Journal of Pharmaceutical Research, 14(2), 211–218
Swain, K., Pattnaik, S., Sahu, S. C., & Mallick, S. (2009). Feasibility assessment of ondansetron hydrochloride transdermal systems: Physicochemical characterization and in vitro permeation studies. Latin American Journal of Pharmacy, 28(5), 706–714.
Formulation and Evaluation of Transdermal Ondansetron Hydrochloride Matrix Patch: In Vitro Skin Permeation and Irritation Study." International Journal of Pharmaceutical Research and Allied Sciences, vol. 13, no. 4, 2024
Pattnaik, S., Swain, K., Mallick, S., & Lin, Z. (2011). Effect of casting solvent on crystallinity of ondansetron in transdermal films. International Journal of Pharmaceutics, 406(1–2), 106–110.
Fathima, F., Kumar, V. B., Rudrangi, S. R. S., Vemula, S. K., Garrepally, P., & Chilukula, S. (2011). Formulation and evaluation of matrix-type transdermal delivery system of ondansetron hydrochloride using solvent casting technique. Research Journal of Pharmacy and Technology, 4(5), 806–814
Alok Ranjan, Aishwarya Sahu, Akansha Yadav, Alka Payasi, Akash Jaiswal, Akshay Kumar, Akash Sahu, Ashwani Jangde, Chandrashekhar Nayak, Dev Kumar, Harshita Yarda, Mitali Sahu, Nokesh Sahu, Rajesh Patel, Nisha Nair, Mukta Agrawal, Ajazuddin, D. K. Tripathi, Amit Alexander. A Short Review on the Formulation of Transdermal Dermal Drug Delivery System (TDDS). Res. J. Pharma. Dosage Forms and Tech. 2018; 10(2): 90-94.
Reference
Vyas S.P., Khar R.K., Controlled Drug Delivery-Concepts and Advances, 1 st Edition, Vallabh Prakashan, 2002, 411- 445
Jain NK (2001) Controlled and novel drug delivery. (1st Edn.) CBS Publisher and Distributors, New Delhi, India 2001: 100-129.
Dhiman S, Thakur G, and Rehni A: Transdermal patches: A recent approach to new drug delivery system. International Journal of Pharmacy and Pharmaceutical Sciences., 2011; 3: 26-34.
Morrow DIJ, McCarron PA, Woolfson AD, and Donnelly RF: Innovative strategies for enhancing topical and transdermal drug delivery. The Open Drug Delivery Journal., 2007; 1: 36-59.
Tortara GJ, Bryan H. Derrickson (2011) Principles of Anatomy and Physiology, (9th Edn.) 140-94.
David SRN, Rajabalaya R, Zhia ES. Development and in vitro evaluation of selfadhesive matrix-type transdermal delivery system of ondansetron hydrochloride. Trop J Pharm Res. 2015;14(2):211–8.
Bhardwaj S, Bhatia S, Singh S. Transdermal Delivery of Ondansetron Hydrochloride in the management of Hyperemesis Gravidarum. Int J Pharma Sci Res. 2020;11(8):206–14.
Misra, A.N. 1997. Controlled and Novel Drug Delivery. In: Jain NK, editors. Transdermal Drug Delivery. New Delhi, India: CBS Publisher and Distributor, pp. 100-101.
Rajabalaya, R., Chen, D.S., David, S.R.N. 2013. Development of transdermal ondansetron hydrochloride for the treatment of chemotherapy-Induced nausea and vomiting. Trop. J. Pharm. Res. 12, 279-285.
Mohd, F. Bontha, L.S., Bontha, V.K., Vemula S.K. 2017. Formulation and evaluation of transdermal films of ondansetron hydrochloride. MOJ Bioequiv Availab. 3, 86-92.
Makoto, S.; Sierra, C.; Naoko, N.; Marina, E.; Alan, Y.; Ruxandra-Ioana, A.; Evelina, P.; Paolo, C.; Ken, Y.; Jason, H.; & Kazuyoshi, A. (2025). Effect of Ondansetron and Metoclopramide on postoperative nausea and vomiting in children undergoing tonsillectomy with or without adenoidectomy: a systematic review with meta- analysis. Journal of Anaesthesia, Vol. 39, pages 345-354, print ISSN 0913-8668 (e-ISSN) is 1438-8359
Chilkoti, Geetanjali T; Nandanan, Janaki; Saxena, Ashok Kumar; Seth, Varun; Kaur, Navneet1; Maurya, Prakriti. Low dose ondansteron with dexamethasone for prophylaxis of postoperative nausea and vomiting following laparoscopic cholecystectomy- A randomized double-blind study. Journal of Anaesthesiology Clinical Pharmacology, Vol. 41, No.1, (Jan-Mar 2025), pp. 84-89, Print ISSN: 0970-9185 Online ISSN: 2231-2730
Sunita N. Vaidya, “Innovations in Topical Drug Delivery: Recent Developments in Transdermal Formulations, Gels, and Patches as Topical Medication Delivery Methods”, AJP, vol. 18, no. 04, Dec. 2024. Print ISSN: 0973-8398, Electronic ISSN: 1998-409X
Patel M, Patel A, Desai J, Patel S. Cutaneous Pharmacokinetics of Topically Applied Novel Dermatological Formulations. AAPS Pharm SciTech. 2024 Feb 27;25(3):46. doi: 10.1208/s12249-024-02763-4. PMID: 38413430. ISSN (Print): 1530-9932, ISSN (Online): 1530-9932
Suksaeree, J., Maneewattanapinyo, P., Panrat, K. et al. Solvent?Cast Polymeric Films from Pectin and Eudragit® NE 30D for Transdermal Drug Delivery Systems. J Polym Environ 29, 3174–3184 (2021). https://doi.org/10.1007/s10924-021-02108-3, ISSN (Print): 1566-2543, ISSN (Online): 1572-8919
Kailash Sahu, Saman Pathan, Kapil Khatri, Neeraj Upmanyu and Satish Shilpi Development, Characterization, In Vitro and Ex Vivo Evaluation of Antiemetic Transdermal Patches of Ondansetron Hydrochloride and Dexamethasone GSC Biological and Pharmaceutical Sciences, 2021, 14(03), 067-078.
Bharathi, D., Reddy, C. S., Babu, G., & Shirisha, Y. (2017). Formulation and Evaluation of Ondansetron HCl Transdermal Patch. World Journal of Pharmaceutical Research, 6(16), 417–426.
Mohd, F., Bontha, L. S., Bontha, V. K., & Vemula, S. K. (2017). Formulation and evaluation of transdermal films of ondansetron hydrochloride. MOJ Bioequivalence & Bioavailability, 3(4), 00039.
Teodorescu, F., Queniat, G., Foulon, C., & Szunerits, S. (2017). Transdermal skin patch based on reduced graphene oxide: A new approach for photothermal triggered permeation of ondansetron across porcine skin. Journal of Controlled Release, 245, 137–146.
David, S. R. N., Rajabalaya, R., & Zhia, E. S. (2015). Development and in vitro evaluation of self-adhesive matrix-type transdermal delivery system of ondansetron hydrochloride. Tropical Journal of Pharmaceutical Research, 14(2), 211–218
Swain, K., Pattnaik, S., Sahu, S. C., & Mallick, S. (2009). Feasibility assessment of ondansetron hydrochloride transdermal systems: Physicochemical characterization and in vitro permeation studies. Latin American Journal of Pharmacy, 28(5), 706–714.
Formulation and Evaluation of Transdermal Ondansetron Hydrochloride Matrix Patch: In Vitro Skin Permeation and Irritation Study." International Journal of Pharmaceutical Research and Allied Sciences, vol. 13, no. 4, 2024
Pattnaik, S., Swain, K., Mallick, S., & Lin, Z. (2011). Effect of casting solvent on crystallinity of ondansetron in transdermal films. International Journal of Pharmaceutics, 406(1–2), 106–110.
Fathima, F., Kumar, V. B., Rudrangi, S. R. S., Vemula, S. K., Garrepally, P., & Chilukula, S. (2011). Formulation and evaluation of matrix-type transdermal delivery system of ondansetron hydrochloride using solvent casting technique. Research Journal of Pharmacy and Technology, 4(5), 806–814
Alok Ranjan, Aishwarya Sahu, Akansha Yadav, Alka Payasi, Akash Jaiswal, Akshay Kumar, Akash Sahu, Ashwani Jangde, Chandrashekhar Nayak, Dev Kumar, Harshita Yarda, Mitali Sahu, Nokesh Sahu, Rajesh Patel, Nisha Nair, Mukta Agrawal, Ajazuddin, D. K. Tripathi, Amit Alexander. A Short Review on the Formulation of Transdermal Dermal Drug Delivery System (TDDS). Res. J. Pharma. Dosage Forms and Tech. 2018; 10(2): 90-94.
Bhawna Sirohi
Corresponding author
HIMT College of Pharmacy, 08, Knowledge Park-1, Greater Noida, Distt. Gautam Buddh Nagar (U.P.)-201310
Bhawna Sirohi*, Hema Negi, A concise review on Development and Assessment of Ondansetron Hydrochloride-Loaded Transdermal Patches, Int. J. Sci. R. Tech., 2025, 2 (6), 631-637. https://doi.org/10.5281/zenodo.15722037
10.5281/zenodo.15722037
