Recebido em 15/3/05; aceito em 3/8/05; publicado na web em 14/3/06 CHITOSAN: HYDROSSOLUBLE DERIVATIVES, PHARMACEUTICAL APPLICATIONS AND RECENT ADVANCES. Chitin and chitosan are copolymers build from N-acetyl-D-glucosamine and D-glucosamine. The former is widely found in nature and yields the latter on deacetylation. The copolymers are being used for several purposes. Since 1977, when the First International Conference on Chitin and Chitosan was held in Boston, USA, the interest on chitin and chitosan has remarkably increased. This review emphasizes pharmaceutical applications of chitosan and its derivatives, and presents recent advances. Some therapeutical applications of these polymers are also discussed.Keywords: chitosan; hydrossoluble derivatives; pharmaceutical applications. INTRODUÇÃOQuitina e quitosana são copolímeros constituídos por unidades Nacetil-D-glicosamina e D-glicosamina em proporções variáveis, sendo que o primeiro tipo dessas unidades predomina no caso de quitina, enquanto quitosana é composta predominantemente, por unidades Dglicosamina 1 . A quitina é o segundo polissacarídeo mais abundante na natureza depois da celulose, sendo o principal componente do exoesqueleto de crustáceos e insetos; sua presença ocorre também em nematóides e parede celular de fungos e leveduras 1 . A quitosana pode ser obtida a partir da quitina por meio da desacetilação com álcalis, podendo também estar naturalmente presente em alguns fungos, como aqueles pertecentes aos gêneros Mucor e Zygomicetes 2 . De acordo com o grau médio de acetilação (GA), parâmetro empregado para caracterizar o conteudo médio de unidades N-acetil-D-glicosamina de quitina e quitosana, podem-se obter diversas quitosanas variando-se, assim, suas propriedades físico-químicas, como solubilidade, pKa e viscosidade 3 . Geralmente, é difícil de se obter quitosana com elevado grau de desacetilação, pois, à medida que este aumenta, a possibilidade de degradação do polímero também aumenta 4 . A Figura 1 representa as estruturas químicas parciais da quitina e quitosana.O emprego de quitina e quitosana e a pesquisa por novas aplicações têm aumentado exponencialmente em diversas áreas, como na agricultura e indústria de alimentos, mas, especialmente, na indústria farmacêutica, no desenvolvimento de cosméticos 5-12 e biomateriais, tais como géis, filmes e membranas poliméricas [13][14][15][16][17] . De acordo com Khor 18 , um aspecto importante na utilização de quitosana diz respeito à sua produção a partir da quitina. Esta deve ser realizada de forma adequada, de maneira que garanta, ao final do processo, a obtenção de quitosana com alto grau de pureza, sobretudo isenta de contaminantes, como proteínas, endotoxinas e metais tóxicos. Neste âmbito, é válido ressaltar que o polímero obtido deve ser caracterizado adequadamente quanto à massa molar, grau de acetilação e distribuição deste grupo ao longo da cadeia polimérica. Estas características podem influenciar na biodegradabilidade do mesmo, principalmente na acessibilidade enzimática, influenciando a hi...

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 CO 2 and CO 2 + 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 CO 2 , 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, CO 2 and ethanol), results showed that, for N-carboxymethyl chitosan, the predominant effects in the impregnation process seemed to be the solubility of drugs in CO 2 and in CO 2 + EtOH mixtures, as well as the swelling and plasticizing effect of CO 2 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.

The measurement and correlation of the experimental solubility of the antimalarial artemisinin (Artemisia annua L.) in supercritical carbon dioxide is reported. Results were obtained using a static analytical method at 308.2, 318.2, and 328.2 K, and in a pressure range from 10.0 up to 25.0 MPa. Solubility experimental data were correlated with three density-based models (Chrastil, Bartle, and Méndez-Santiago-Teja models) and with two cubic equation of state (EOS) models, namely, the Peng-Robinson EOS and the Soave-Redlich-Kwong EOS, together with the conventional van der Waals mixing and combining rules. Good correlation results were obtained between the calculated and the experimental solubility to all fitted models. Results clearly show the feasibility of processing this antimalarial drug using supercritical fluid technologies and processes.