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The purpose of this study was to investigate the effect on solubility and dissolution rate of binary complexes of β-(βCD), methyl-(MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) with diloxanide furoate (DF). The complexation in solution was evaluated by phase solubility studies and 1H nuclear magnetic resonance (NMR). Enhanced water solubility of DF was obtained with the DF:MβCD system (61-fold). The mode of inclusion was supported by NMR experiments, which indicated that real inclusion complexes were formed between DF and MβCD or HPβCD. Solid state analysis was performed using infrared and thermal methods, which suggested the formation of true inclusion complexes of DF with two derivatized cyclodextrins, MβCD and HPβCD, and an exclusion complex with βCD when the systems were prepared by freeze-dried technique. Dissolution studies conducted in simulated gastric fluid (2 h) and subsequent simulated intestinal fluid (next 4 h) showed increased dissolution rate of DF from the freeze-dried systems with βCD, MβCD, and HPβCD (85; 77 and 75% of dissolved drug at 5 min, respectively) and 100% of the drug dissolved at 150 min for the three systems. The enhancement of the solubility and the dissolution of DF observed make these complexes promising candidates for the preparation of oral pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Poorly soluble drug-loaded liposomes are well known for their ability to solubilize and improve the bioavailability of the carried molecules, and may provide benefits as oral drug delivery systems. In this work, we aim to evaluate the effect of the incorporation of β-cyclodextrin (βCD), methyl-βCD (MβCD), hydroxypropil-βCD (HPβCD) and meglumine (MEG) in liposomes for the oral delivery of the poorly water-soluble drugs, sulfamerazine (SMR) and indomethacin (INM). Liposomes with egg phosphatidylcholine (PC) and cholesterol (CHO), incorporating SMR or INM as plain drug or inclusion complexes, were prepared using the thin film hydration method or dehydration-rehydration method, respectively. The systems were characterized by particle size, polydispersity and zeta potential measurements, and drug-component interaction studies were performed by 1 H NMR. Liposome stability in presence of SMR, INM, CD and MEG was determined by the retention of vesicle encapsulated calcein after incubation in solutions of pH 7.4, at 37 °C for up to 48 h. Drug entrapment, as well as drug release, were estimated for all liposome types prepared. The 1 H NMR studies revealed that the drugs presented interaction with lipids of the liposomes, suggesting the location of the drugs in the lipid bilayer. The liposomes presented high stability in the presence of the drugs, βCD, HPβCD or MEG. The highest entrapment values were achieved for SMR and INM with PC:CHO 3:1 liposomes when MEG and HPβCD were used, respectively (5636.28 and 439.54 mmol/mol), meaning that 18 and 43 times higher incorporation of SMR and INM were achieved in comparison with the ligand-free formulation. The in-vitro release studies showed a strong influence of the ligands on the delivery of the drugs from the liposomes. [ABSTRACT FROM AUTHOR]

Cyclodextrins (CDs) and meglumine (MEG) are pharmaceutical excipients widely used to improve solubility of poorly water-soluble drugs. The purpose of this work was to study the effect of CDs or MEG on the internal microstructure of soya oilebased O/W microemulsions (MEs) and on the modulation of the solubility and release rate of Class II model hydrophobic drugs, sulfamerazine and indomethacin. The pseudoternary phase diagrams revealed that higher proportions of oil phase, as well as the presence of β-cyclodextrin (βCD), methyl-βCD, and MEG, favored the incorporation of the drugs. The conductivity studies, particle size, and zeta potential analysis showed that the O/W ME structure remained unaffected and that the ME presented reduced droplet sizes after the incorporation of the ligands. The drugcomponent interactions were assessed by proton nuclear magnetic resonance studies. The highest incorporations of sulfamerazine (35.6 mg/mL) and indomethacin (73.1 mg/mL) were obtained with the ME with W = 5%, MEG and W = 1.8% βCD in a phosphate buffer solution of pH 8, respectively. In addition, the ligands in ME significantly enhanced the released amount of the drugs, probably due to a solubilizing effect that facilitates the drug to penetrate the unstirred water layer adjacent to membranes. [ABSTRACT FROM AUTHOR]

This study investigated the effect on solubility and release of ternary complexes of sulfamerazine (SMR) with β-(βCD), methyl-(MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) using meglumine (MEG) as the ternary component. The combination of MEG with MβCD resulted the best approach, with an increased effect (29-fold) of the aqueous solubility of SMR. The mode of inclusion was supported by 2D NMR, which indicated that real ternary complexes were formed between SMR, MEG and MβCD or HPβCD. Solid state analysis was performed using Fourier-transform infrared spectroscopy (FT IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD), which demonstrated that different interactions occurred among SMR, MEG and MβCD or HPβCD in the ternary lyophilized systems. The ternary complexes with βCD and MβCD produced an additional retention effect on the release of SMR compared to the corresponding binary complexes, implying that they were clearly superior in terms of solubility and release modulation. [ABSTRACT FROM AUTHOR]

In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with β-cyclodextrin (βCD), methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and a binary system with meglumine (MEG) were developed. The formation of 1:1 inclusion complexes of SMR with the CDs and a SMR:MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a Smax of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of βCD, MβCD, HPβCD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes. [ABSTRACT FROM AUTHOR]