No abstract

Benznidazole (BNZ) is the drug of choice for Chagas disease treatment, which affects about 9.8 million people worldwide. It has low solubility and high toxicity. The present study aimed to develop and characterize inclusion complexes (IC) in binary systems (BS) with BNZ and randomly methylated-β-cyclodextrin (RMβCD) and in ternary systems (TS) with BNZ, RMβCD and hydrophilic polymers. The results showed that the solid BS had a large increase in dissolution rate (Q>80%). For the solid IC obtained, the kneading method, in ratio of 1:0.17 (77.8% in 60 min), appeared to be the most suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and low concentration of CD. The solid TS containing 0.1% of hydroxypropylmethylcellulose (HPMC) showed no significant advantages compared to the binary IC in solid state. The use of cyclodextrins proved to be a viable tool for effective, standardized and safe drug delivery.

The results show that BNZ only undergoes direct photodegradation, since no new PPs were found for a combination of the drug and excipients.

The current chemotherapy for Chagas disease is still based on benznidazole, which has low solubility, but complexation with cyclodextrins provides a way of increasing the solubility. The objective of this work was to characterize the inclusion complexes formed between benznidazole (BNZ) and randomly 2-methyled-b-cyclodextrin (RM-b-CD) in aqueous solution and study cytotoxicity and trypanocidal. BNZ:RM-b-CD solution complex systems were prepared and characterized using the phase solubility diagram, nuclear magnetic resonance and a photostability assays, also to investigate the in vitro trypanocidal activity with epimastigote forms of Trypanossoma cruzi and the study of cytotoxicity against mammal cells. The phase-solubility diagram displayed an A L -type feature, providing evidence of the formation of soluble inclusion complexes. The continuous variation method showed the existence of a complex with 1:1 stoichiometry. Toxicity assays demonstrated that inclusion complexes were able to reduce the toxic effects caused by benznidazole alone and that this did not interfere with the trypanocidal activity of the benznidazole. The use of inclusion complexes benznidazole:cyclodextrin is thus a promising alternative for the development of a safe and stable liquid formulation and a new option for the treatment of Chagas disease.

Developed originally as an antimalarial agent, hydroxychloroquine sulfate (HCQS) is often used as a slow-acting drug in treating disorders of connective tissue. Over the past two decades, several data have been accumulated on the systemic effects of HCQS, expanding the potential uses of this drug in different therapeutic classes. The purpose of this article was to conduct a narrative review with qualitative approach on clinical, pharmacokinetic and technological aspects of HCQS, aiming to gather relevant pieces of information for the development of new therapeutic approaches to this drug. A search of the literature of scientific experimental and theoretical studies in the period 1980-2013 was performed. According to the data collected, among the activities HCQS, there are the indications for the treatment of autoimmune diseases such as lupus erythematosus and rheumatoid arthritis. Reports also indicate that HCQS improves insulin sensitivity, ability to reduce thromboembolic events, reduction of lipid levels and treatment for infection by human immunodeficiency virus. The evidence found out ocular and cutaneous adverse effects and the formation of three chiral active metabolites, what encourages studies to evaluate the kinetic behavior of HCQS and the intrinsic physicochemical characteristics of the drug, which is yet poorly described in the literature.