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

• Published in: AAPS PharmSciTech 2008, Vol.9 (3), p.1038-1045
• Main Authors: Nishikawa, Masato, Onuki, Yoshinori, Isowa, Koichi, Takayama, Kozo
• Format: Article
• Language: English
• Subjects: Acrylic Resins - administration & dosage; Acrylic Resins - chemistry; Acrylic Resins - radiation effects; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - radiation effects; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chemistry, Pharmaceutical; Cross-Linking Reagents - administration & dosage; Cross-Linking Reagents - chemistry; Cross-Linking Reagents - radiation effects; Hydrogels - administration & dosage; Hydrogels - chemistry; Hydrogels - radiation effects; Indomethacin - administration & dosage; Indomethacin - chemistry; Indomethacin - radiation effects; Male; Pharmacology/Toxicology; Pharmacy; Photochemistry; Rats; Research Article; Skin - drug effects; Skin - metabolism; Ultraviolet Rays
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-008-9141-x

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 anti-inflammatory 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.