Gamma oryzanol niosomal gel for skin cancer: formulation and optimization using quality by design (QbD) approach

Harsh S Shah,Aditi Bariya,Amarjitsing Rajput,Dolly Jetha,Ankit Gotecha,Shital Butani,Shital Panchal

doi:10.1186/s41120-021-00041-2

Harsh S Shah, Aditi Bariya + Show 5 more

Open Access

https://doi.org/10.1186/s41120-021-00041-2

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Abstract

Skin cancer is fifth most diagnosed disease in human population due to ultraviolet radiation (UV) exposure. Gamma oryzanol (OZ) is a natural antioxidant, and it also has skin anti-aging properties. OZ is naturally found in rice bran oil. The main aim of the present work was to optimize OZ niosomal formulation using quality by design approach including one variable at a time and full factorial design. Niosomes were prepared by solvent injection method and characterized for size, polydispersity index, drug entrapment, and transmission electron microscopy. The optimized batch obtained at X1 [drug to span 60 molar ratio (1:5)], X2 [volume of hydration (75 mL)], and X3 [stirring speed (2500 rpm)] to Y1 [average vesicle size (196.6 nm)] and Y2 [entrapment efficiency (78.31%)] as dependent variables. The optimized OZ noisomes were formulated by niosomal gel to provide improved physicochemical stability upon topical application against UV. The niosomal gel was characterized using pH meter, viscometer, Draize test for skin irritancy, ex vivo permeation studies, and stability studies. Ex vivo permeation studies of OZ niosomal gel not only showed fourfold higher permeation but also exhibited better drug retention in dermal layers of skin as compared to OZ gel. Quality Target Product Profile of OZ niosomal formulation was generated. Risk analysis of optimized OZ gel suggested most critical quality attributes (CQAs) and critical process parameters (CPPs) to be characterized as low risk. Thus, γ-oryzanol niosomal gel for topical use can serve as a promising prophylactic treatment in skin cancer, and the developed prototype formulation can be further extended to future newly discovered drugs with similar characteristics.Graphical abstract

Highlights

Drug administration via transdermal route has been evolving as one of the most preferred alternative routes for drug delivery
The transdermal delivery systems have been widely used ranging from the treatment of cutaneous disorders or cutaneous manifestation to some general disorders due to its systemic effect
The formulation scientists must be cautious about the limitation associated with transdermal delivery systems, wherein the skin barrier properties may lead to inadequate drug permeation transdermally

Summary

Introduction

Drug administration via transdermal route has been evolving as one of the most preferred alternative routes for drug delivery. Transdermal delivery systems have clear advantages over oral drug administration as first pass metabolism is avoided; factors such as gastrointestinal pH, effect of food, and peristaltic movement will not be applicable to reap the therapeutic benefits of a particular active pharmaceutical ingredient. A relatively lipophilic drug in a lipidic drug delivery system can deal with diffusivity problem to a great extent. This concept is being intensively investigated for the skin cancer treatment (Manosroi et al 2012; Rawal et al 2018; Tagne et al 2008; Zeinali et al 2021)

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