Evaluations of Quality by Design (QbD) Elements Impact for Developing Niosomes as a Promising Topical Drug Delivery Platform

Abstract

Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery system that may be used to deliver desoximetasone via topical product application in order to mitigate common side effects associated with traditional oral delivery routes. The aim of this research was to identify the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of drug-loaded niosomes using a systematic quality by design (QbD) approach. An organic phase injection method was developed and used to manufacture the niosomes. The CMAs were identified to be drug amount, concentrations of surfactant and cholesterol, and types of lipids. The CPPs were phase volumes, temperature, mixing parameters, and addition rate based on previous research. The quality attributes measured were entrapment efficiency, particle size distribution, PDI, and zeta potential. These were used to determine the quality target product profile (QTPP) of niosomes. The experimental data indicate that the critical impacting variables for niosomes are: surfactant and cholesterol concentrations, mixing parameters, and organic-phase addition rate. Based on the experimental results of this study methanol:diethyl ether (75:25) as the organic system, drug:surfactant:cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate is the ideal combination to achieve desirable desoximetasone niosomes with optimum entrapment efficiency and particle size for topical application.

Nanostructured Non-Ionic Surfactant Carrier-Based Gel for Topical Delivery of Desoximetasone

“…Niosomes were developed using an ether injection method by completely dissolving the drug into the organic phase, which was dropwise added to an aqueous phase using magnetic stirring and finally stored separately in glass storage sample containers. Identified during previous studies, Critical material attributes (CMAs) organic phase, drug concentration, surfactant concentration, cholesterol concentration, and lipid types, and critical processing parameters (CPPs) external phase temperature, external phase volume, internal phase volume, mixing speed, mixing time, and rate of addition utilizing a systematic 2 5 full factorial design using advanced statistical device JMP ® -enabled DoE approach [6,38]. Formulation composition: containing drug/surfactant/cholesterol (1:2:1), diethyl ether/methanol (75:25), external phase temperature (65 • C), external phase volume/internal phase volume (2:1), mixing speed (650 rpm), mixing time (50 min), and addition rate (0.5 mL/min) successfully developed a final niosome formulation with 90.12 ± 0.02% entrapment efficiency, 449.40 ± 29.2 nm particle size, 0.272 ± 0.03 PDI and −73.50 ± 0.87 mV zeta potential.…”

Nano intervention in topical delivery of corticosteroid for psoriasis and atopic dermatitis—a systematic review

“…The desired desoximetasone niosomes had methanol:diethyl ether (75:25) as the organic system, drug:surfactant: cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate with optimum entrapment efficiency ranging from 63.90 to 95.58%, particle size, and PDI ranging from 154.40 to 919.87 nm and 0.144 to 0.441, respectively. Thus, comprehensive research on the understanding of drug product design for the formulation of dexamethasone noisome could be further incorporated into a suitable vehicle for topical application against skin conditions such as allergic reactions, AD, and psoriasis [ 48 ].…”

Surfactants, Nanomedicines and Nanocarriers: A Critical Evaluation on Clinical Trials

“…The general conclusion is that translation of scientific research into a clinical application represents a major challenge, where the main and critical issue is the toxicity and safety evaluation. Other manuscripts highlight, in fact, how the quality by design approach would be envisaged for the development of nanopharmaceutical products in order to limit risks due to high variability in quality [ 6 , 7 ]. A modern formulation approach to the design of experiments has also been reported, but again, in this case, it is, at the same time, highlighted that translation of certain nanomedicines from the laboratory to market has been very limited [ 8 ].…”