Investigation of Silicone-Containing Semisolid in Situ Film-Forming Systems Using QbD Tools

Abstract

The aim of our research work was to develop dermally applicable, semisolid film-forming systems (FFSs) containing silicones, which form a film on the skin in situ, with suitable mechanical properties for skin application. FFSs were developed and investigated by means of the Quality by Design (QbD) methodology. With this QbD approach, the initial risk assessment defines the critical quality attributes (CQAs), the critical material attributes (CMAs) and the critical process parameters (CPPs) to ensure the required quality. Different semisolid systems were formed with or without silicones. During the initial risk assessment, three CQAs, namely skin adhesion, film flexibility and burst strength, were found to be critical attributes, while film appearance, film integrity and the drying time of the semisolid system, were found to be medium attributes. These parameters were investigated. The initial risk assessment also showed that there are three high CMAs: the type of silicones, film-forming excipients, drying excipients, and that there was one medium CMA: viscosity-enhancing excipients. Based on our results, the silicone content had a great effect on the film-forming systems. Different silicones affected the mechanical properties of the films in varying ways, decreased the drying time and showed promising results regarding the drying mechanism.

<p>QbD-Based Investigation of Dermal Semisolid in situ Film-Forming Systems for Local Anaesthesia</p>

“…These are the critical material attributes (CMAs) and the critical process parameters (CPPs), which include properties of the API and excipients (eg, emollient, polymer), and properties of the applied process (eg, type of technology, homogenization time and rate). 18,27 Risk Assessment: Quality Tools Risk assessment is in the focus of the QbD approach. During risk management, the risks of the product quality are assessed, controlled, communicated, and reviewed.…”

“…Volatile silicones improve the film-forming ability, and more favorable drying time can be achieved. 18 The optimal mechanical properties ensure that the films are retained on the skin surface for a longer time, thereby increasing exposure time. To improve patient adherence, films need to be removable painlessly, and the drying time needs to stay in a convenient range.…”

“…25 Based on our previous research, in situ FFSs could be a good choice to ensure painless local anaesthesia. 18 The aim of this work was to develop LID-HCl-containing semisolid in situ FFSs using the QbD approach. The purpose of using QbD approach is to select the influencing attributes of the investigated system, which is essential for future development steps, such as defining product and process design space, and defining control strategy.…”

“…ST -Cyclomethicone 5 -NF was the volatile silicone component to ensure the drying properties and to increase the permeation through the skin. 18,29,30 Additional nonvolatile silicones, Dimethiconol Blend 20, ST -Elastomer 10, and 7-3101 Elastomer Blend HIP Emulsion were added to F2, LF2 and F3, LF3, to modify film formation and rigidity of films. 12 Furthermore, they modify the appearance of the film, provide a "silky touch" feeling, protect and soften the skin.…”

“…PVA and Xanthan gum also enhance film formation and have viscosity increasing properties. 12,18 Additionally, ethanol is a drying excipient and a permeation enhancer excipient as well. 30 LID-HCl was dissolved in Ethanol 96% and PVA was dissolved separately in purified water at 80°C under mixing.…”