Inclusion complexes of sulfanilamide with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin

Sulfanilamide belongs to the group of drugs that have a bacteriostatic effect on different pathogenic microorganisms. This activity originates from the competitive antagonism with p-aminobenzoic acid, which is an integral part of folic acid. The safe use of sulfanilamide is limited due to poor solubility in the aqueous medium. Therefore, the aim of this paper is the synthesis of sulfanilamide, as well as preparing and structural characterization of its inclusion complexes with cyclodextrins. The crude sulfanilamide was obtained in the synthesis between acetanilide and chlorosulfonic acid according to the standard procedure. The synthesized sulfanilamide was recrystallized from water in order to obtain the satisfactory purity of the substance. Sufanilamide was complexed with β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin by the co-precipitation method. A molecular encapsulation of sulfanilamide was confirmed by using FTIR, ¹H-NMR, XRD and DSC methods. Phase-solubility techniques were used to assess the formation of the inclusion complex between sulfanilamide and cyclodextrins. The photostability of sulfanilamide and its inclusion complexes was estimated by UVB irradiation in a photochemical reactor by applying the UV–Vis method. Based on the UV–Vis analysis, sulfanilamide:2-hydroxypropyl-β-cyclodextrin complex was presented as more photostable than sulfanilamide:β-cyclodextrin complex and sulfanilamide. The obtained results enable the potential use of these inclusion complexes for the preparation of oral formulations due to the enhanced solubility of sulfanilamide.     

Binding of vitamin A byβ-cyclodextrin and heptakis(2,6-O-dimethyl)-β-cyclodextrin

Inclusion complexation of all-trans-retinol, retinal and retinoic acid with -cyclodextrin (-CD) and heptakis(2,6-O-dimethyl)--cyclodextrin (DM--CD) were investigated by means of UV-vis spectroscopy. The association constants (K _a) obtained for vitamin A with DM--CD is greater than with -CD. On the other hand, for the same host compoundK _a values of retinol, retinal and retinoic acid are very close to each other.     

Complex formation of cinnamaldehyde-methyl-β-cyclodextrin and muscone-methyl-β-cyclodextrin by supercritical carbon dioxide processing and sealed heating method

Firstly, the interaction between cinnamaldehyde (CIN) and methyl-β- cyclodextrin (MBCD) was studied in aqueous solution. 1:1 inclusion complex was formed and the association constant was 187 ± 9 M^?1. Then the complex of CIN–MBCD and muscone–MBCD was prepared both by sealed heating method and by supercritical carbon dioxide (sc CO₂) approach. Complete complex was obtained by both methods for CIN–MBCD. Some CIN molecules was weakly associated with MBCD molecules in products by sealed heating method, all CIN molecules was strongly associated with MBCD molecules in products by sc CO₂ processing. Complete complex between muscone and MBCD was not obtained. The choice for the size of guest molecule still existed for MBCD cavity in sealed heating method and sc CO₂ processing.     

Solubility and molecular modeling of triflumizole-β-cyclodextrin inclusion complexes

Solubility enhancement of the fungicide triflumicole by-cyclodextrin is explained using a thermodynamic approach. The influence of organic cosolvents on the overall equilibrium constants of triflumizole complexation with-cyclodextrin in aqueous solutions has been investigated. Their variance in mixed solvents is only partly explained by a competitive inclusion of substrate and cosolvent molecules in-cyclodextrin. The geometries of host-guest complexes have been estimated by molecular mechanics calculations. Their broad structural variety caused by the flexibility of host and guest molecules and different association possibilities of triflumizole have been analysed by a dynamic Monte Carlo docking method. The hydrophobic effect has been simulated by cominimization of the hydrophobic contributions to the solvation energy, calculated from the solvent accessible surface area of the complex and the conformational (potential) energy.     

Investigation of Ethacrynic Acid and Random-methyl-β-cyclodextrin Binary Complexes

Cyclodextrin complexation was applied to achieve better aqueous solubility of the drug and to formulate suppositories. Binary products were prepared in several mole ratios by two different methods. The dissolution profiles and in vitro membrane diffusion behaviour of the compositions were investigated. Thermoanalytical studies were performed in order to confirm inclusion complex formation. Compositions were selected for further detailed investigations and for incorporation into suppository dosage form.     

Physicochemical characterization of sanguinarine-hydroxypropyl-β-cyclodextrin binary and ternary systems

Complexation of sanguinarine with hydroxy-propyl-β-cyclodextrin (HPβCD) in the presence and absence of hydrophilic polymer—polyvinylpyrrolidone K30 was studied. Respective binary and ternary systems were prepared using two techniques, physical mixture and lyophilization, and characterized by FT-infrared spectrometry, differential scanning calorimetry and X-ray diffractometry. The Fourier Transform Infrared spectra of the lyophilized binary and ternary systems showed significant shifts in the regions of 1240–1300 cm^?1, 1450–1525 cm^?1 and 1600–1650 cm^?1, where absorptions of –C–O–C– asymmetrical stretching of sanguinarine rings A and F and ν_C=C ring vibrations of sanguinarine benzo[c]phenanthridine system can be observed respectively. Moreover, in the case of ternary products ν_C=O amide band absorption of polyvinylpyrrolidone (1600–1750 cm^?1) shifted to the lower wavenumbers in both the physical mixture and the lyophilized product. These changes in the spectra of the studied systems proved the involvement of the respective molecular groups in complexation process. Differential scanning calorimetry and X-ray diffractometry indicated different states of drug amorphization and entrapment in HPβCD in the presence and without polyvinylpyrrolidone. The obtained results let us conclude that obtained binary and ternary systems represent sanguinarine-HPβCD molecular complexes, with different rate of inclusion in the presence and without polyvinylpyrrolidone.     

Solid state amorphization and glass transition of tri-O-methyl-β-cyclodextrin

Amorphous solid of tri-O-methyl--cyclodextrin was formed by grinding the crystalline sample with a vibrating mill at room temperature. The amorphising process was examined by X-ray powder diffraction technique and differential scanning calorimetry (DSC). The Bragg peaks disappeared and the enthalpy of crystallization became constant for the sample ground for 25 min, indicating the apparent completion of the amorphization. A glass transition of the ground amorphous solid was found by DSC. The glass transition temperature T_g moved from 58°C to 79°C with grinding. The saturated T_g of the ground sample was the same as that of the liquid-quenched glass. No significant difference between the ground and liquid-quenched amorphous solids was found in the X-ray diffraction patterns. Infrared spectra of both amorphous solids, however, showed a definite difference for the band at 1194 cm^–1 assigned to the rocking of the CH₃ groups which are located at the molecular periphery.

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Zusammenfassung Amorphes festes Tri-O-methyl--cyclodextrin wurde bei Raumtemperatur durch Mahlen einer kristallinen Probe in einer Vibrationsmühle hergestellt. Der Amorphisierungsprozeß wurde mittels Röntgenpulverdiffraktion und DSC verfolgt. Die Braggschen Peaks verschwanden und die Kristallisierungsenthalpie nahm nach einem Mahldauer von 25 min einen konstanten Wert an, was auf die augenscheinliche Beendigung des Amorphisierungsprozesses hinweist. Mittels DSC wurde ein Glasumwandlungspunkt des gemahlenen amorphen Feststoffes gefunden. Die Glasumwandlungstemperatur T_g stieg durch das Mahlen von 58°C auf 79°C. Der Sättigungswert T_g der gemahlenen Probe war der gleiche wie für flüssigkeitsabgeschrecktes Glas. In den Röntgendiffraktogrammen konnte zwischen den gemahlenen und den flüssigkeitsabgeschreckten amorphen Feststoffen keinen Unterschied feststellen. Die IR-Spektren von beiden amorphen Feststoffen zeigen einen signifikanten Unterschied für die Bande bei 1194 cm^–1, der Nickschwingung der CH₃-Gruppen am Molekülrand.

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Dedicated to Professor Dr. H. J. Seifert on the occasion of his 60^th birthday

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Contribution No. 35 from the Microcalorimetry Research Centre.

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The authors thank the research group of Professor Yoshinobu Nakai, Faculty of Pharmaceutical Science, Chiba University, for their kind advice for the grinding-amorphization method. The authors are deeply indebted to Mr. Tetsuo Yamamoto for his X-ray diffraction experiments and Mr. Shin-ichi Ishikawa for his IR experiments.     

Composition and properties of freeze-dried products of nicotinic acid withβ-cyclodextrin and heptakis (2,6-0-dimethyl)-β-cyclodextrin

The purpose of the study was to examine the formation of inclusion compounds in the freeze-dried products obtained from aqueous solutions of nicotinic acid and -cyclodextrin (-CD), or heptakis (2,6-0-dimethyl)--cyclodextrin (DIMEB). The molar ratios used were 1:1 and 2:1. In addition two freezing temperatures (–40 and –196°C) and different secondary drying temperatures (+50 and +80°C) were used. Freeze-dried products with -CD obtained after low temperature freezing are of the same crystallographic structure as seen in a pure inclusion compound prepared by coprecipitation. Amorphous products were formed after fast freezing. The molar ratios of included nicotinic acid in the freeze-dried products vary — dependent on the preparation conditions — between 0.75:1 and 1:1. A factorial design proves that the included drug amount can be increased by enhancement of the amount of nicotinic acid used, by faster freezing, and by the combination of these two factors. The proof of inclusion formation was given by a combination of X-ray diffractography, differential scanning calorimetry, thermogravimetry and thermofractography.The freeze-dried preparations obtained with DIMEB were amorphous mixtures of the two components. No proof for inclusion of the nicotinic acid in the cyclodextrin cavity could be given. Higher (–40°C) or lower (–196°C) freezing temperatures and the running of the secondary drying process could not influence these results. The very low stability constant of the complex and steric reasons are responsible for this behavior.     

FT-IR and raman spectra of a series of metallo-β-cyclodextrin complexes

A series of metallo--CD complexes were prepared and formulated as [M₂(OH)₂ -CD·2 H₂O] ^n– . Changes in the FT-IR and Raman Spectra of-CD on coordination may be taken as evidence for complexation and support for a hydroxy bridged binuclear structure. Further support was obtained from uv/visible and magnetic moment measurements.     

Preparation and characterization of inclusion complexes of carvedilol with methyl-β-cyclodextrin

Aim of the present work was to investigate the effect of methyl-β-cyclodextrin (MβCD) on the solubility and dissolution rate of carvedilol (CAR), a drug used orally for the treatment of hypertension. Phase solubility studies showed an A_L-type diagram indicating the formation of inclusion complex in 1:1 molar ratio. Solid binary systems of the drug with MβCD were prepared by various methods. Physicochemical characterizations were performed using Fourier Transformation Infrared Spectroscopy, Differential Scanning Calorimetry and powder X-Ray Diffractometry. It could be concluded that CAR can form inclusion complex with MβCD. The dissolution profiles of inclusion complexes were determined and compared with those of CAR alone and the physical mixture. The dissolution rate of CAR was increased by MβCD inclusion complexation remarkably.     

Silylation of 2-hydroxypropyl-β-cyclodextrin

The effect of the reaction conditions or the nature of the silylating agents on the silylation of hydroxypropyl-β-cyclodextrin with tert-butyldimethylchloro- and diphenyl-methylchlorosilanes is investigated.     

Alkyl capped carbonates ofβ-cyclodextrin

The synthesis is described of alkyl capped carbonates of-cyclodextrin, obtained from diols activated with carbonyldiimidazole. The reaction preferentially gave monocapped derivatives which were characterized by HPLC, TLC, FT-IR and¹³C-NMR. These compounds are stable at pH <7, and methyl orange was found to form stronger inclusion compounds with capped-cyclodextrin than with the parent-cyclodextrin. Paramagnetic Gd(III) complexes were also studied, but they were found to be included into capped-cyclodextrin as well as into-cyclodextrin.Part of this work was presented at the 7th International Symposium on Cyclodextrins, 1994, Tokyo, April 25–28, Book of Abstract, page 54.     

Preparation and evaluation of binary and ternary inclusion complexes of fenofibrate/hydroxypropyl-β-cyclodextrin

This study aimed to investigate the effect of hydroxypropyl methylcellulose on the complexation of fenofibrate and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, phase solubility studies with an excess amount of drug in the HP-β-CD solutions with and without hydroxypropyl methylcellulose (HPMC) were investigated. Both of the binary and ternary complexes were prepared by ball-milling. The complexes were characterized by Fourier transform infrared spectroscopy (FI-IR), X-ray powder diffraction (XPRD), differential scanning calorimetry (DSC) and nuclear magnetic resonance spectroscopy (¹H-NMR). The A_L type phase-solubility diagram revealed that the complexes of fenofibrate and HP-β-CD were formed with molecular ratio of 1:1. The results of FT-IR, XPRD, DSC and ¹H NMR analysis show the formulation of inclusion complexes. In conclusion, the interaction occurrs between fenofibrate and HP-β-CD in the complexes, and the existence of HPMC effectively improves the complexation efficiency and stability constant. The in vitro dissolution test suggests ternary complex is superior to binary complex in terms of the release of fenofibrate.     

Preparation and characteristics of hydroxypropyl-β-cyclodextrin polymeric nanocapsules loading nimodipine

Nimodipine loaded hydroxypropyl-β-cyclodextrin polymeric nanocapsules were prepared by interfacial polyaddition of hydroxypropyl-β-cyclodextrin and isophorone diisocyante in a miniemulsion system. The effects of ultrasonicate times on the preparation of miniemulsion, the total amount of hydroxypropyl-β-cyclodextrin and isophorone diisocyante, and the molar ratio of isophorone diisocyante to hydroxypropyl-β-cyclodextrin on the capsule size and drug release behavior from capsule were investigated. The chitosan based polymeric nanocapsules were prepared as a control to study the effect of hydroxypropyl-β-cyclodextrin molecules in capsule matrix on the drug release. The results indicated that the droplet size of miniemulsion and capsule size decreased with increasing sonicate times. When the total amount of hydroxypropyl-β-cyclodextrin and isophorone diisocyante, and the molar ratio of isophorone diisocyante to hydroxypropyl-β-cyclodextrin were increased, the capsule as well, but the drug release rates from capsules became slower. The drug release behaviors from hydroxypropyl-β-cyclodextrin polymeric nanocapsules were affected by the drug diffusion through the polymer matrix and the formation of inclusion complex between drug and hydroxypropyl-β-cyclodextrin.     

Influence of hydroxypropyl-β-cyclodextrin on the photostability and antiradical activity of Trolox

Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a derivative of vitamin E, can undergo photolysis upon UV irradiation. In the present study the photodegradation kinetics of Trolox were thus investigated in different systems in the absence and in the presence of titanium dioxide, a physical sunscreen present in several cosmetic products, that can act as photocatalyst. In all the considered media Trolox degraded under UVB light following pseudo-zero order kinetics, probably by a mechanism of photooxidation. The rate of Trolox photodegradation was lower in O/W emulsions than in aqueous solution and in gel; furthermore it was significantly influenced by the presence of TiO₂. Aiming to increase Trolox stability, it was complexed with hydroxypropyl-β-cyclodextrin: the inclusion complex was characterized by phase solubility studies, spectrophotometry and differential scanning calorimetry. The irradiation experiments indicated that complexation with hydroxypropyl-β-cyclodextrin was effective in reducing the photodegradation rate of Trolox. Moreover the host molecule favored the uptake of Trolox into the porcine skin, as shown by in vitro permeation studies. Nevertheless the assay of peroxidation, based on the reaction of malondialdehyde with thiobarbituric acid, indicated that the antioxidant activity of Trolox was maintained even after inclusion in cyclodextrin.     

Preparation and characterization of theβ-cyclodextrin inclusion complex with sulfafurazole

The 1 : 1 inclusion complex involving sulfafurazole (SF) and-cyclodextrin (-CD) is prepared by the freeze-drying method and characterized on the basis of its chemical analysis, thermal behavior, infrared spectrum, X-ray powder pattern and¹³C NMR spectrum in DMSO-d₆ solution. The stability constant of the inclusion complex was determined by the solubility method. The effect of cyclodextrin on the UV absorption spectrum of sulfafurazole was also observed.     

Thermoanalytical and spectroscopic characterization ofβ-cyclodextrin/ketoprofen inclusion complexes

A method to determine the composition and hydration state of the complexes formed in aqueous solution by cyclodextrins (CD) is presented and applied to the -CD/ketoprofen system; it is based on a combination of spectroscopic, calorimetric, and thermogravimetric analyses. The complexes have, on average and per -CD mole, more than eleven water molecules, which are present in completely different bound states.     

Synthesis and characterization of praseodymium-2-hydroxypropyl-β-cyclodextrin inclusion complex

Journal of Radioanalytical and Nuclear Chemistry - The inclusion complex of PrCl3-XH2O-2-hidroxypropyl-β-cyclodextrin (Pr-2HPβCD) was prepared to increase the solubility and stability of...     

Supramolecular Complex of 2-Hydroxypropyl-β-cyclodextrin with d- and l-tryptophan

Cyclodextrins are known by their properties of molecular recognition. In the present work, it was established, by using high-performance liquid chromatography, that complexes between 2-hydroxypropyl-β-cyclodextrin (HPCD) and d- and l-tryptophan are readily formed in solution. Association constants of (2 ± 1) × 10 and of (9 ± 2) × 10^? 1 for d and l-isomers, respectively, were calculated from UV electronic spectroscopy experiments. Solid state complexes were characterized by Fourier-transform infrared spectroscopy, which showed that the subtracted/deconvoluted spectra present wavenumber changes of the NH₃ ⁺ asymmetric angular deformation and of the COO^?  asymmetric stretching.