Characterisation and controlled drug release from novel drug-loaded hydrogels

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 69; no. 3; pp. 1147 - 1159
• Main Authors: Geever, Luke M., Cooney, Ciaran C., Lyons, John G., Kennedy, James E., Nugent, Michael J.D., Devery, Sinead, Higginbotham, Clement L.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.08.2008; Elsevier Science
• Subjects: Acrylamides; Acrylic Resins; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Biological and medical sciences; Calorimetry, Differential Scanning; Cell Survival - drug effects; Cells, Cultured; Cross-Linking Reagents; Delayed-Action Preparations - chemistry; Diclofenac - administration & dosage; Diclofenac - chemistry; Drug delivery; General pharmacology; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - toxicity; Lower critical solution temperature; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photopolymerisation; Polymers; Povidone; Procaine - administration & dosage; Procaine - chemistry; Solubility; Spectroscopy, Fourier Transform Infrared; Temperature; Temperature sensitive; Tetrazolium Salts; Thiazoles; Ultraviolet Rays; Temperature sensitive; Drug delivery; Hydrogels; Photopolymerisation; Lower critical solution temperature; Drug; Pharmaceutical technology; Controlled release form; Toxicity; Drug carrier; Colloidal gel; Dosage form; Hydrogel; Critical temperature; Solution
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2007.12.021

Hydrogel based devices belong to the group of swelling controlled drug delivery systems. Temperature responsive poly( N-isopropylacrylamide)–poly(vinylpyrrolidinone) random copolymers were produced by free radical polymerisation, using 1-hydroxycyclohexylphenyketone as an ultraviolet-light sensitive initiator, and poly(ethylene glycol) dimethacrylate as the crosslinking agent (where appropriate). The hydrogels were synthesised to have lower critical solution temperatures (LCST) near body temperature, which is favourable particularly for ‘smart’ drug delivery applications. Two model drugs (diclofenac sodium and procaine HCl) were entrapped within these xerogels, by incorporating the active agents prior to photopolymerisation. The properties of the placebo samples were contrasted with the drug-loaded copolymers at low levels of drug integration. Modulated differential scanning calorimetry (MDSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and atomic force microscopy (AFM) were used to investigate the influence of the drugs incorporated on the solid-state properties of the xerogels. MDSC and swelling studies were carried out to ascertain their effects on the LCST and swelling behaviour of the hydrated samples. In all cases, drug dissolution analysis showed that the active agent was released at a slower rate at temperatures above the phase transition temperature. Finally, preliminary in vitro cytotoxicity evaluations were performed to establish the toxicological pattern of the gels.