Binary and ternary inclusion complexes of dapsone in cyclodextrins and polymers: preparation, characterization and evaluation

Abstract

Dapsone (DAP) is a synthetic sulfone drug with bacteriostatic activity, mainly against Mycobacterium leprae. In this study we have investigated the interactions of DAP with cyclodextrins, 2-hydroxypropyl-b-cyclodextrin (HPbCD) and b-cyclodextrin (bCD), in the presence and absence of water-soluble polymers, in order to improve its solubility and bioavailability. Solid systems DAP/HPbCD and DAP/bCD, in the presence or absence of polyvinylpyrrolidone (PVP K30) or hydroxypropyl methylcellulose (HPMC), were prepared. The binary and ternary systems were evaluated and characterized by SEM, DSC, XRD and NMR analysis as well as phase solubility assays, in order to investigate the interactions between DAP and the excipients in aqueous solution. This study revealed that inclusion complexes of DAP and cyclodextrins (HPbCD and bCD) can be produced in order to improve DAP solubility and bioavailability in the presence or absence of polymers (PVP K30 and HPMC). The more stable inclusion complex was obtained with HPbCD, and consequently HPbCD was more efficient in improving DAP solubility than bCD, and the addition of polymers had no influence on DAP solubility or on the stability of the DAP/CDs complexes.

1 H NMR studies of binary and ternary dapsone supramolecular complexes with different drug carriers: EPC liposome, SBE-β -CD and β -CD

“…The architectural arrangement of Dap / β ‐CD was proposed based on detailed data provided by the 1D ROESY. Such results have already been presented in the preceding texts in different experimental conditions; however, we repeated the experiments paying special attention to the selective 180° pulse used in the 1D ROESY and quantification by integrating the ROE values to obtain a detailed structure of the complex. The signal enhancements revealed dipolar cross relaxations between β ‐CD H3 and Dap Ha and Hb (0.64 and 0.34%, respectively) and between β ‐CD H5 and Dap Ha and Hb (1.79 and 0.90%, respectively).…”

“…The structure of the Dap / β ‐CD complex was sensitive to the NMR experimental parameters. Thus, in our experiments, Dap was fully inserted into β ‐CD, similar to some complexes studied by 1 H NMR but different from others suggested based on emission spectroscopy . However, atomic level interactions are specially observed by NMR spectroscopy, producing more accurate information regarding the architecture of the supramolecular complexes.…”

“…However, our aim to evaluate the change in chemical shift is only qualitative because the strength of the interaction was studied from variation in the diffusion coefficient of substances. The Dap / β ‐CD complex has been previously characterised; however, its characterisation on the same experimental conditions used for all drug carriers addressed in this study was important for better data comparison. Moreover, these data have to be consistent for a better understanding of the ternary complex formation containing Dap, EPCL and β ‐CD.…”

“…Dap and β ‐cyclodextrin ( β ‐CD) interactions have been studied by applying different methodologies, and their apparent association constants in the presence and absence of various linear alcohols were determined by spectrofluorimetry . Dap‐ β ‐CD complex stoichiometry has been reported, and several structural models were proposed based on emission spectroscopy and nuclear magnetic resonance (NMR) experiments. Additionally, ternary systems composed of Dap, polyvinylpyrrolidone K30 or hydroxypropyl methylcellulose, and β ‐CD or 1‐HP‐ β ‐CD were investigated to improve Dap solubility and bioavailability .…”

“…Dap‐ β ‐CD complex stoichiometry has been reported, and several structural models were proposed based on emission spectroscopy and nuclear magnetic resonance (NMR) experiments. Additionally, ternary systems composed of Dap, polyvinylpyrrolidone K30 or hydroxypropyl methylcellulose, and β ‐CD or 1‐HP‐ β ‐CD were investigated to improve Dap solubility and bioavailability . Liposomes have been extensively applied as drug carriers, particularly egg phosphatidylcholine liposome (EPCL), which, together with β ‐CD and the local anaesthetic proparacaine, make stable ternary complexes …”