Supramolecular Arrangement of Doxycycline with Sulfobutylether-ß-Cyclodextrin: Impact on Nanostructuration with Chitosan, Drug Degradation and Antimicrobial Potency.

Doxycycline (DX) is a well-established and broad-spectrum antimicrobial drug. However, DX has drawbacks, such as physicochemical instability in aqueous media and bacterial resistance. The inclusion of drugs in cyclodextrin complexes and their loading into nanocarriers can overcome these limitations. Thus, we studied the DX/sulfobutylether-ß-CD (SBE-ß-CD) inclusion complex for the first time and used it to reticulate chitosan. The resulting particles were evaluated by their physicochemical characteristics and antibacterial activity. DX/SBE-ß-CD complexes were characterized by nuclear magnetic resonance, infrared spectroscopy, thermal analysis, X-ray diffraction, and scanning electron microscopy (SEM), whereas DX-loaded nanoparticles were characterized by dynamic light scattering, SEM, and drug content. The partial inclusion of the DX molecule in CD happened in a 1:1 proportion and brought increased stability to solid DX upon thermal degradation. Chitosan-complex nanoparticles measured approximately 200 nm, with a narrow polydispersity and particles with sufficient drug encapsulation for microbiological studies. Both formulations preserved the antimicrobial activity of DX against Staphylococcus aureus, whereas DX/SBE-ß-CD inclusion complexes were also active against Klebsiella pneumoniae, indicating the potential use of these formulations as drug delivery systems to treat local infections.

Amino acids and its pharmaceutical applications: A mini review.

Amino acids are natural compounds that can be safely used in pharmaceutical applications. Considering the great interest in the amino acids used in the pharmaceutical industry, this article presents an overview of investigations reported in recent years. In this regard, the first sections begin with an introductory description of the properties, classification and safety of amino acids, while in the other sections the most common methods for the preparation of amino acids formulations and their application on solubilization, permeation and stabilization of several active pharmaceutical ingredients are described. Furthermore, available data about the multicomponent systems approach is included. Lastly, the impact of amino acids formulations on therapeutic efficacy is explored. The advantages illustrated suggest that amino acids are capable of improving the biopharmaceutical properties of drugs.

ß-cyclodextrin complexation as an approach to enhance the biopharmaceutical properties of Norfloxacin B Hydrate.

Binary systems of Norfloxacin B Hydrate with ß-CD were explored by reliable biopharmaceutical studies as potential candidates for the preparation of drug delivery systems. Initially, studies of antimicrobial activity and solubility of the different polymorphic forms of Norfloxacin provided evidence to select Norfloxacin B Hydrate as the optimal solid form of Norfloxacin. Solid binary systems were preparing by kneading, freeze-drying, and physical mixture methods. The influence on the solubility, dissolution rate and chemical stability of Norfloxacin B Hydrate was investigated. These studies showed an increment of solubility and dissolution rate in physiological simulated fluids. However, the solid systems were moderated hygroscopically under accelerated storage conditions, which produces a destabilizing effect that accelerated the chemical reactivity of the drug in such conditions. Therefore, special cares must be considered in the manufacturing process and the packaging selection. Moreover, the experimental results proved that freeze-drying was not an appropriate method for the preparation. In conclusion, the Norfloxacin oral bioavailability can be improved with this binary systems, that could be applied in the production of an alternative pharmaceutical formulation of the drug.

Synthesis and characterization of supramolecular systems containing nifedipine, ß-cyclodextrin and aspartic acid.

The purpose of this work was to characterize complexes of nifedipine with ß-cyclodextrin (ß-CD), with and without auxiliary agents, to improve aqueous solubility and the dissolution profile of nifedipine. Complexes were characterized using infrared spectroscopy, thermoanalytical methods, powder X-Ray diffraction, scanning electron microscopy, phase solubility analysis and dissolution studies. Spatial configurations were determined by NMR and further examined using computational techniques. This investigation showed that the amino acid Asp was the most efficient auxiliary agent for multicomponent complexes. The spatial configurations were consistent with those obtained by molecular modelling; evidencing that nifedipine inserted its aromatic ring into ß-CD, in all complexes, with Asp interacting with the wide hydrophilic rim of ß-CD. The dissolution rates of nifedipine:ß-CD:Asp complexes were significantly increased compared to those of the pure drug or nifedipine:ß-CD. These results indicate that the nifedipine:ß-CD:Asp system is a promising approach for the preparation of optimized formulations of nifedipine.

Cross-linked hyaluronan films loaded with acetazolamide-cyclodextrin-triethanolamine complexes for glaucoma treatment.

AIM: This work aimed to design and characterize cross-linked hyaluronic acid-itaconic acid films loaded with acetazolamide-hydroxypropyl ß cyclodextrin-triethanolamine complexes. MATERIALS & METHODS: Films were cross-linked with itaconic acid and poly(ethyleneglycol)-diglycidylether. Biopharmaceutical properties were assessed by evaluating in vitro drug release rate, biocompatibility in a human corneal epithelial cell line, bioadhesiveness with pig gastric mucin, in vivo bioadhesion and efficacy. RESULTS: Showed good mechanical properties and oxygen permeability. Proliferation rate of corneal cells was affected by highest acetazolamide concentration. Bioadhesive interaction exhibited a water movement from pig mucin to the film; in vivo experiments showed strong bioadhesion for 8 h and hypotensive effect for almost 20 h. CONCLUSION: Experimental set showed promising performance and encouraged future studies to optimize formulation. [Formula: see text].

Influence of ß-cyclodextrin on the Properties of Norfloxacin Form A.

Cyclodextrins are able to form host-guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and ß-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and ß-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with ß-cyclodextrin as demonstrated by a solubility isotherm of the AL type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of ß-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.

Increasing doxycycline hyclate photostability by complexation with ß-cyclodextrin.

Doxycycline hyclate (DOX) is a highly photosensitive drug, a feature that limits the stability of the corresponding dosage forms. The main objectives of this work were the preparation and characterization of an inclusion complex of DOX with ß-cyclodextrin (ßCD) and to investigate if this approach could improve the photostability of the drug. Guest-host interactions were investigated using nuclear magnetic resonance, which were afterwards combined with molecular modeling methods to study the complex formation and its three-dimensional structure was proposed. A freeze-drying method was applied to obtain the complex in the solid state, which was further confirmed by thermal and spectroscopic techniques. To evaluate the complexation effect on DOX integrity, the photostability of the inclusion complex was studied, with a significant decrease in the photodegradation of DOX being found in aqueous solution upon complexation. Finally, the photoprotection produced by the complexation was evaluated by means of an antimicrobial assay. Overall, the presented results suggest that the formulation of DOX complexed with ßCD constitutes an interesting approach for the preparation of pharmaceutical dosage forms of DOX with enhanced stability properties.

Binding of sulfamethazine to ß-cyclodextrin and methyl-ß-cyclodextrin.

ß-cyclodextrin (ßCD) and methyl-ß-cyclodextrin (MßCD) complexes with sulfamethazine (SMT) were prepared and characterized by different experimental techniques, and the effects of ßCD and MßCD on drug solubility were assessed via phase-solubility analysis. The phase-solubility diagram for the drug showed an increase in water solubility, with the following affinity constants calculated: 40.4±0.4 (pH 2.0) and 29.4±0.4 (pH 8.0) M(-1) with ßCD and 56±1 (water), 39±3 (pH 2.0) and 39±5 (pH 8.0) M(-1) with MßCD. According to (1)H NMR and 2D NMR spectroscopy, the complexation mode involved the aromatic ring of SMT included in the MßCD cavity. The complexes obtained in solid state by freeze drying were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and thermal analysis. The amorphous complexes obtained in this study may be useful in the preparation of pharmaceutical dosage forms of SMT.