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Research Article

Quality by Design Approach for Preparation, Characterization, and Statistical Optimization of Naproxen Sodium-loaded Ethosomes via Transdermal Route

Author(s): Ananda Kumar Chettupalli*, Srivani Ajmera, Padmanabha Rao Amarachinta, Ram Mohan Manda and Rajendra Kumar Jadi

Volume 19, Issue 10, 2023

Published on: 07 July, 2023

Article ID: e060623217712 Pages: 20

DOI: 10.2174/1573407219666230606142116

Price: $65

Abstract

Aim: The primary goal of this study is to create a novel naproxen sodium-loaded ethosome drug delivery system for improving bioavailability, solubility and optimize using a statistical approach.

Background: Naproxen sodium (i.e., a non-steroidal anti-inflammatory drug) is chosen as the first line of treatment for rheumatoid arthritis and ankylosing spondylitis. However, naproxen has side effects, such as bronchospasm, an irregular heart rhythm, etc. Therefore, adopting new drug delivery strategies when developing the dosage form is necessary and the need of the hour to prevent its side effects. The available commercial products are administered through the oral and parenteral routes, which lack bioavailability and permeability respectively.

Objective: Novel ethosomal carriers were designed using Box Behnken Design (BBD) and formulation was prepared for enhanced topical delivery of naproxen sodium ethosomal gel.

Methods: In order to analyze the data statistically and graphically with response surface plots, the Box-Behnken design was used to optimize the formulation variables. The independent factors were phosphatidylcholine (X1), cholesterol (X2), and ethanol (X3), while the dependent variables were entrapment efficiency (Y2), vesicle size (Y1), and PDI (Y3). The Carbopol® 940 gel was then made using the improved ethosomes. Its rheological properties, in-vitro release, ex-vivo skin penetration, and deposition were studied.

Results: The best ethosomes were made by mixing phosphatidylcholine and cholesterol in a phosphate buffer at pH 7.4 with 2–5% v/v ethanol. The optimized ethosomes showed a zeta potential of -32.06 ± 0.16 mV, EE of 84.59 ± 2.38%, and a vesicular size of 105 ± 6.97 nm. Compared to the commercial products and the ethanolic solution of naproxen, these ethosomes considerably increased the amount of naproxen permeated through the skin over 24 hours. The stability of the optimized formulation was assessed for three months at room temperature, and it was found that the efficiency of the prepared novel ethosomal formulation remained intact.

Conclusion: In summary, it was discovered that the ethosomal vesicles were potential carriers, showing the improved topical distribution of naproxen sodium. These findings demonstrated that using ethosomes as a transdermal medication carrier for naproxen was feasible. Compared to drug solutions, the ex-vivo permeation and skin deposition experiments produced better results.

Graphical Abstract

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