Formulation Optimization of an Indomethacin-Containing Photocrosslinked Polyacrylic Acid Hydrogel as an Anti-inflammatory Patch

Abstract

Abstract. Photocrosslinked polyacrylic acid hydrogel, made from polyacrylic acid (PAA) modified with 2-hydroxyethyl methacrylate (HEMA), is a promising candidate adhesive for dermatological patches. In this study, we investigated the further availability of hydrogel as an adhesive for dermatological patches using a hydrogel containing indomethacin (IDM) as a model anti-inflammatory patch. From an orthogonal experimental study, we clarified the relationships between formulation factors and characteristics of model formulation. Formulations with a lower degree of swelling were prepared by increasing the degree of HEMA modification and the addition of Tween 80. Apparent permeation rate was increased by addition of L-menthol and Tween 80. A tendency for higher HEMA modification to be accompanied by the prolongation of the lag time of IDM was observed. To obtain an applicable antiinflammatory patch, we conducted a formulation optimization study using a novel optimization method, a response-surface method incorporating multivariate spline interpolation (RSM-S). Consequently, a highly functional anti-inflammatory patch in terms of its adhesive properties and bioavailability was successfully obtained. Since a wide range of functions can be fully controlled by manipulating the formulation factors, photocrosslinked polyacrylic acid hydrogel is an attractive candidate adhesive for dermatological patches.

Adhesive properties: a critical issue in transdermal patch development

“…The application as wound dressing and electrically conductive pads was also reported [50]. These types of hydrophilic PSAs consisting of swollen polymers require a chemical or photo cross-linking to increase their very low creep resistance [51,52]. Very few investigations deal with alternative strategies in order to avoid a final curing, which could determine a physical or chemical instability of the loaded drugs.…”

A Novel Approach to Establishing the Design Space for the Oral Formulation Manufacturing Process

“…In fact, this method has already been applied to practical cases for both formulation development and manufacturing process development and has already demonstrated its effectiveness. [9][10][11][12][13] In addition, it is important to evaluate the reliability of the design space, and to determine its conservative border to clarify the credibility inside the border of the design space. Although the reliability of the design space derived from a linear response surface model using polynomial equations can be evaluated by statistical analysis, the reliability of the design space derived from a nonlinear response surface model estimated by RSM-S cannot be directly evaluated by statistical analysis.…”

Reliability Evaluation of Nonlinear Design Space in Pharmaceutical Product Development

“…The dissolution test apparatus was used for the dissolution test with paddles method (JP XV) at 50 rpm using 900 mL of JP XV second fluid (pH 6.8; 0.05 M H 2 KPO 4 and 0.0236 M NaOH) at 37 • C with stirring at 50 rpm. The samples were withdrawn and filtered after 3, 6,9,12,15,20,30, and 40 min. The indomethacin concentration was measured spectrophotometrically at 320 nm with a Jasco Ubest-30 spectrophotometer (Japan Spectroscopic Company, Ltd., Tokyo, Japan).…”

“…In addition, this method does not require any complicated methodology such as an artificial neural network, and it has been applied to practical cases to optimize pharmaceutical formulations. [12][13][14][15] It is not always easy to ensure quality with a high probability when a tablet formulation or process parameter is located at the border of the design space, and it becomes necessary to clarify the credibility inside the border of the design space. However, the reliability of the nonlinear response surface estimated by RSM-S cannot be evaluated directly using conventional statistical quantities.…”