Claudia Garnero

Studies on trimethoprim:hydroxypropyl-β-cyclodextrin: aggregate and complex formation

The present study is focused on the characterization of the interaction between trimethoprim, a dihydropteroate synthesase inhibitor, and hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solution and solid state. The freeze-drying method was used to prepare solid complexes, while simple blending was employed to obtain physical mixtures. The phase solubility was AN type, and demonstrated that trimethoprim solubility was significantly increased upon complexation with HP-β-CD. Conductivity experiments showed the presence of aggregates that explains the type profile for the solubility isotherm. The critical concentration for the aggregate formation was determined to be 69.3mg/ml for pure HP-β-CD and 117.7 mg/ml in the presence of trimethoprim. Nuclear magnetic resonance spectroscopy provided evidence of trimethoprim:HP-β-CD molecular interaction in solution. Moreover, the complex was characterized in solid stated using Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The use of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the thermal stability of the drug is enhanced in the presence of HP-β-CD.

Sulfamethoxazole:hydroxypropyl-β-cyclodextrin complex: preparation and characterization

A complex of sulfamethoxazole (SMX) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was developed and characterized in order to investigate their interactions in aqueous solution and the solid state. The SMX solubility was significantly increased upon complexation with HP-β-CD, with the solubility isotherm being an A(N) type due to the presence of aggregates and the stability constant calculated for a 1:1 complex being 302 ± 3 M⁻¹. Fourier-transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) experiments were used to compare the freeze-dried system with a physical mixture, and demonstrated the complex formation in the solid state. The differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the thermal stability of SMX was enhanced in the presence of HP-β-CD.

Development of HPLC and UV spectrophotometric methods for the determination of ascorbic acid using hydroxypropyl-β-cyclodextrin and triethanolamine as photostabilizing agents

In this study, the effect of complex formation with triethanolamine (TEA) alone and in combination with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the photostability of ascorbic acid was evaluated for exposure to artificial and diffuse daylight. The first-order rate constants for the photodegradation reactions were determined. The data obtained showed that these complexes strongly reduced the photodegradation process with an 11- and 35-fold increase in the photostability of ascorbic acid, depending of the ligand concentration and the irradiation source. The multicomponent complex gave a significantly better stabilization for exposure to light than TEA alone. Due to the fact that the complexation extended the exposure of ascorbic acid to light (without molecular changes), UV spectrophotometric and reversed phase high performance liquid chromatographic (HPLC) methods were developed for the quantitative determination of the vitamin in pure form and in pharmaceutical preparations. These methods were statistically validated, all the validation parameters were found to be within the acceptance range. These results demonstrate that the proposed methods are suitable for the quality control of ascorbic acid, providing simple, rapid, precise, accurate and convenient approaches for routine analysis of bulk drug and pharmaceutical formulations.

Second derivative spectrophotometric determination of trimethoprime and sulfamethoxazole in the presence of hydroxypropyl-β-cyclodextrin (HP-β-CD)

Abstract An easy and rapid second-derivative spectrophotometric method for the simultaneous analysis of trimethoprime (TMP) and sulfamethoxazole (SM) is described. These drugs have been used as antibacterial against a wide spectrum of organisms and combinations of these drugs are commonly used for the treatment of a variety of infections. The most advantageous approach of this method is the use of HP-β-CD, which allows to improve the performance of the second-derivative ultraviolet spectrophotometry. For both compounds, a shift of the absorption bands and variations of their intensity were observed. The calibration graphs were linear in the concentration range of TMP (1.92–19.2 μg ml −1 ) and SM (1.60–16.5 μg ml −1 ), the correlation coefficient for the calibration graphs was better than 0.9994 and the precision was satisfactory (CV%

Investigating Albendazole Desmotropes by Solid-State NMR Spectroscopy

Characterization of the molecular structure and physicochemical solid-state properties of the solid forms of pharmaceutical compounds is a key requirement for successful commercialization as potential active ingredients in drug products. These properties can ultimately have a critical effect on the solubility and bioavailability of the final drug product. Here, the desmotropy of Albendazole forms I and II was investigated at the atomic level. Ultrafast magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy, together with powder X-ray diffraction, thermal analysis, and Fourier transform infrared spectroscopy, were performed on polycrystalline samples of the two solids in order to fully characterize and distinguish the two forms. High-resolution one-dimensional (1)H, (13)C, and (15)N together with two-dimensional (1)H/(1)H single quantum-single quantum, (1)H/(1)H single quantum-double quantum, and (1)H/(13)C chemical shift correlation solid-state NMR experiments under MAS conditions were extensively used to decipher the intramolecular and intermolecular hydrogen bonding interactions present in both solid forms. These experiments enabled the unequivocal identification of the tautomers of each desmotrope. Our results also revealed that both solid forms may be described as dimeric structures, with different intermolecular hydrogen bonds connecting the tautomers in each dimer.

Supramolecular complexes of maltodextrin and furosemide polymorphs: a new approach for delivery systems

We present new supramolecular complexes of two different solid forms of furosemide (I or II) with maltodextrin, in order to explore their application as delivery systems improving the bioavailability of the drug. The complexation in solution was evaluated by (1)H nuclear magnetic resonance experiments and phase solubility studies. The products in solid state were exhaustively characterized by using spectroscopic techniques ((13)C solid state nuclear magnetic resonance, infrared, scanning electron microscopy, X-ray powder diffractometry) and thermal analysis. (1)H relaxation times experiments gave further support in distinguishing the new solid forms. Dissolution studies in simulated gastric fluid showed that both supramolecular complexes presented significant increase in the dissolution, while the corresponding physical mixtures exhibited the most discriminating conditions between the furosemide forms I and II. Our results suggest the enhancement of the solubility and the dissolution of furosemide in the new complexes, making them promising candidates for the preparation of alternative matrices in oral pharmaceutical formulations.

Improving furosemide polymorphs properties through supramolecular complexes of β-cyclodextrin.

In this work, complexes of β-cyclodextrin and the two solid forms of furosemide were prepared and characterized for their potential pharmaceutical applications, with the interactions between the two compounds being studied in the solution and solid states. The solubility studies revealed different behaviors of the polymorphs. In particular, it was observed that the binary complex significantly increased the solubility of furosemide form I in the gastric simulated fluid, which resulted in a rise in the bioavailability of this formulation after oral administration. In addition, results using ssNMR, FT-IR, DSC, TGA, SEM and XRPD provided evidence of the formation of complexes after utilizing kneading and freeze-drying methods. A comparison with previous developed complexes that used maltodextrin as the ligand was performed. Our results suggest that these novel supramolecular complexes showed promise to be used in drug delivery systems with an application in pharmaceutical formulations.

Insights into Novel Supramolecular Complexes of Two Solid Forms of Norfloxacin and β-Cyclodextrin

The solid-state properties of novel complexes of β-cyclodextrin and two different solid forms of norfloxacin were investigated at the molecular level, in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. In order to evaluate the physical properties inherited from the different polymorphs, these supramolecular systems were characterized using a variety of spectroscopic techniques including natural-abundance (13) C cross-polarization magic-angle-spinning (CP-MAS) nuclear magnetic resonance (NMR), powder X-ray diffraction, and Fourier transform infrared spectroscopy. The intrinsic proton spin-lattice relaxation times detected in (13) C CP-MAS NMR spectra are used to confirm and distinguish the complex formation, as well as to provide better insights into the molecular fragments that are involved in the interaction with β-cyclodextrin.

Toward novel antiparasitic formulations: Complexes of Albendazole desmotropes and β-cyclodextrin

Novel complexes of two different solid forms of Albendazol and β-cyclodextrin were investigated in an attempt to obtain promising candidates for the preparation of alternative matrices used in pharmaceutical oral formulations. The interaction between each form of Albendazol and β-cyclodextrin was studied in solution and solid state, in order to investigate their effect on the solubility and dissolution rate of Albendazol solid forms. The solid supramolecular systems were characterized using a variety of techniques including natural-abundance 13C cross-polarization magic-angle-spinning nuclear magnetic resonance, powder X-ray diffraction, Fourier transform-infrared spectroscopy and scanning electron microscopy. The results obtained showed the highest increment of solubility and dissolution rate, in simulated gastric fluid, for the Albendazole II:β-cyclodextrin systems. Thus, these new complexes constitute an interesting alternative for improving the oral bioavailability of Albendazol.

Influence of β-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 β-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 β-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with β-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 β-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug.