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Title: Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives
Authors: Braga, Mara E. M. 
Pato, Maria T. Vaz 
Silva, Hélio S. R. Costa 
Ferreira, Elisabeth I. 
Gil, Maria H. 
Duarte, Catarina M. M. 
Sousa, Hermínio C. de 
Keywords: N-chitosan derivatives; Ophthalmic drug delivery systems; Supercritical solvent impregnation (SSI); Flurbiprofen; Timolol maleate
Issue Date: 2008
Citation: The Journal of Supercritical Fluids. 44:2 (2008) 245-257
Abstract: In this work, three chitosan derivatives (N-carboxymethyl chitosan (CMC), N-carboxybutyl chitosan (CBC) and N-succinyl chitosan (SCC)) were impregnated with flurbiprofen (an anti-inflammatory drug) and timolol maleate (an anti-glaucoma drug), using a supercritical solvent impregnation (SSI) technique (and employing high pressure CO2 and CO2 + EtOH mixtures) in order to develop hydrogel-type ophthalmic drug delivery applications. Impregnation experiments were carried out from 9.0 up to 14.0 MPa, and at 303.0, 313.0 and 323.0 K. The resulting polymeric drug delivery systems, as well as other polymeric samples processed in CO2, were characterized by FTIR spectroscopy and scanning electron microscopy (SEM). Drug release kinetics studies were performed for all prepared systems. The effects of impregnation pressure and temperature on the release kinetics results were studied and compared to the traditional soaking impregnation method. For the same operational conditions, results confirmed that the three different (chemically and physically) polymeric structures conditioned the impregnation and the drug release processes. Despite the final released drug mass is always the result of the employed operational impregnation conditions and of the very complex relative specific interactions that may occur between all species present in the system (drugs, polymers, CO2 and ethanol), results showed that, for N-carboxymethyl chitosan, the predominant effects in the impregnation process seemed to be the solubility of drugs in CO2 and in CO2 + EtOH mixtures, as well as the swelling and plasticizing effect of CO2 and ethanol on the polymer. Finally, the SSI method proved to be a more efficient and "tunable" impregnation process than the traditional impregnation of drugs by a soaking method. Therefore, and using this "tunable" SSI method, these N-chitosan derivatives-based ophthalmic drug delivery systems can be easily and efficiently prepared taking in consideration the desired drug levels according to patients needs.
Rights: openAccess
Appears in Collections:FCTUC Eng.Química - Artigos em Revistas Internacionais

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