Study of the Influence of Formulation Variables in Bioadhesive Emulgels Using Response Surface Methodology

Abstract

The aim of the present work was to study the main formulation variables that influence attributes of bioadhesive emulgels based on a combination of polymers, using response surface methodology (RSM). Bioadhesive products continue to gain attention in topical cutaneous administration as they allow long residence times on the application site, which is important when a long dermal action and a reduced product administration frequency are desired. A Box-Behnken design of experiments (DoE) was introduced to study the effect of formulation variables on quality attributes of the emulgels. The effects of concentration of carbomer interpolymer type A (Polym1), xanthan gum (Polym2) and mineral oil (Oil) on detachment force (Fdetch), spreadability (Spread), and phase separation by mechanical stress (PhSep) were investigated. RSM and desirability functions were applied for data analysis. Emulgels were further characterized by viscosity and extrudability measurements. Polym1 showed a positive effect on Fdetch, while the increase in concentrations of Polym2 and Oil decreased this property. Polym1 and Polym2 favored emulgel PhSep. However, their interaction effect decreased it. The combination of 0.4-0.6% of carbomer and 0.2-0.3% of gum was able to produce easy-to-spread bioadhesive emulgels with mineral oil as discontinuous phase in the presence of a low surfactant concentration. Based on the DoE results, value ranges for the variables, which could achieve for the experimental domain to get the critical quality attributes of emulgels jointly within the specification limits, were able to be identified using RSM supported by desirability functions.

Preparation and evaluation of caffeine bioadhesive emulgels for cosmetic applications based on formulation design using QbD tools

“… † Phase separation observed after centrifugation stress of formulation. Predicted value obtained from checkpoint analysis for PhSep = 0 [7]. …”

“… * Detachment forces obtained by texturometer measurements using 50 mm diameter stainless cylindrical probe, nude and covered with full thickness human skin. Predicted value obtained from checkpoint analysis for Fdetach = 0.540 N [7]. …”

“…The rational characterization of the emulgels based on our DoE results allowed the selection of three parameters, Spread, PhSep and Fdetach, as critical quality attributes of the product [7]. In addition, viscosity and viscoelastic characterizations were performed using a rotational viscometer and an oscillatory rheometer, respectively.…”

“…Three critical quality attributes of emulgels were identified: detachment force (Fdetach), spreadability (Spread) and phase separation (PhSep) as function of polymers and mineral oil composition. In addition, the validity of the mathematical model was confirmed by checkpoint of formulation variables and an optimized bioadhesive emulgel formulation without active compounds was developed [7].…”

“…In our previous work, bioadhesive emulgel formulations based on binary combinations of two bioadhesive gelling agents, carbomer interpolymer type A (Carbopolâ Ultrez 10) and xanthan gum, were developed using Quality by Design (QbD) tools [7]. QbD refers to the achievement of certain predictable quality with desired and pre-determined specifications.…”