Characterization Of Inclusion Complexes Research Articles

Production and Characterization of a β-Cyclodextrin Inclusion Complex with Platonia insignis Seed Extract as a Proposal for a Gastroprotective System

Platonia insignis Mart, Clusiaceae, known as bacuri, is a species native to Brazil that, in studies with extract of the seed of its fruit, showed antioxidant activity against free radicals. Products with such properties may be of great importance in the treatment of peptic ulcers since this pathology may be associated with the inflammatory process caused by the action of free radicals. Cyclodextrins are molecules capable of forming inclusion complexes with other molecules, affecting their physicochemical properties and improving their pharmacokinetic characteristics. Thus, this work aimed to produce, characterize, and evaluate the gastroprotective effect of the inclusion complex of β-cyclodextrin (β-CD) with the bacuri seeds hexanic extract (BSHE). In the characterization of the inclusion complex, an apparent stability constant (Kc) of 416 mol/L was obtained in the solubility study; the BSHE:β-CD m/m (g) complexation ratios at 1:9, 2:8, and 3:7 were 5.51%, 21.46%, and 20.11%, respectively. The formation of the BSHE:β-CD inclusion complex was observed by FTIR technique, indicating the disappearance of bands characteristic of BSHE (2960 cm−1 and 1755 cm−1) when in the complex, compared to the spectra of pure BSHE or in physical mixture with β-CD, and by X-ray diffraction, which indicated a loss of crystallinity, typical signals of pure β-CD, and presentation of intense amorphization, characteristic of BSHE, incorporated in the β-CD pockets. In the evaluation of gastroprotective activity, through absolute ethanol-induced gastric lesions in mice, both BSHE and BSHE:β-CD reduced gastric lesions, with 100 mg/kg dose of the complex having the greatest gastroprotective effect. BSHE:β-CD was also able to reduce gastric lesions from ischemia and reperfusion, with the 50 mg/kg dose being the most effective. BSHE:β-CD, also at this dose, reduced the MDA levels of the gastric mucosa, indicating a possible antioxidant activity in its gastroprotective effect. Thus, it was concluded that inclusion complex formation between β-CD and BSHE is possible, and that this formulation enhanced the gastric protective activity.

Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-β-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Preparation and Spectroscopic Characterization of Inclusion Complexes of 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin : 3D Ball-Milled Rifampicin with β-cyclodextrin and γ-cyclodextrin.

Rifampicin (RFP) solutions, intended to reduce incidence of prosthetic graft infection, were prepared as three-dimensional ground mixtures (3DGMs) using β-cyclodextrin (βCD) and γ-cyclodextrin (γCD) and characterized for their spectroscopic properties and solubility. Phase solubility diagrams revealed that 3DGMs (RFP/βCD and RFP/γCD) produced a complex at 1:1 molar ratio. Pulsed field gradient nuclear magnetic resonance experiments indicated that the diffusion coefficients for RFP/βCD and RFP/γCD were similar to the respective diffusion coefficients for βCD and γCD. Rotating-frame Overhauser effect spectroscopy NMR spectra revealed the existence of a new exchanger peak for RFP/γCD, suggesting an intermolecular interaction different from that of RFP/βCD. Differential scanning calorimetry confirmed the presence of endothermic peak at 191°C indicating the manifestation of RFP in the inclusion complex. Interestingly, molecular interactions from the complexes, RFP/βCD and RFP/γCD, revealed different patterns of inclusion in the 3DGMs. In RFP/βCD, nuclear Overhauser effect spectroscopy NMR spectra indicated cross peaks for the protons of the methyl group of RFP and the protons (H-5 and H-6) in the βCD cavity. The methyl group of RFP interacted with the narrow rim of βCD. With RFP/γCD, cross peaks were due to the protons of the methyl group of RFP and the protons of the cavity of γCD suggesting multiple inclusion patterns. The observed multiple cross peaks affirm the inclusion of RFP into the CD cavity which enhanced its solubility by 1.6-2.0-fold when prepared as 3DGMs as RFP/βCD and RFP/γCD, respectively.

Host-guest inclusion complexes of sulfabenzamide with β- and methyl-β-cyclodextrins: Characterization, antioxidant activity and DFT calculation

The inclusion complexation behavior, characterization and binding ability of sulfabenzamide (SBZ) with β-cyclodextrin (β-CD) and methyl-β-cyclodextrin (Mβ-CD) have been investigated both in solution and solid state by different experimental techniques. Sulfabenzamide drug having poor water solubility and slow dissolution. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The spectral shifts revealed that part of aniline ring of SBZ is entrapped in the CD cavity. The association constants were determined by Benesi-Hildebrand plots and spectroscopic studies. The phase solubility studies were carried using two different types of cyclodextrins viz., β, methyl-β cyclodextrins. The phase solubility profiles with all the two cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, FTIR, 1HNMR, XRD and SEM studies. We investigated the interaction of the host–guest Mβ-CD/SBZ complex by means of molecular dynamics simulation using a density functional based tight-binding code (DFT).

Preparation and Characterization of Silver Cyclohexane Mono Carboxylate : β-Cyclodextrine Inclusion Complexes and Obtaining Wash-Resistant Antibacterial Effect on Cotton Fabrics

In this study, inclusion complexes were prepared according to kneading and physical mixing techniques at 1:1 and 1:2 (guest:host) mass ratios of silver cyclohexane mono carboxylate:β-cyclodextrin. Prepared complexes were analyzed by using fourier transformed infrared spectroscopy, thermogravimetric analyses and scanning electron microscope. With regard to the obtained results, inclusion complex formation was observed with silver cyclohexane mono carboxylate and β-cyclodextrin at a mass ratio of both 1:1 and 1:2. In addition to preparation and characterization of inclusion complexes, they were applied on cotton fabrics via pad-dry method. In order to investigate the wash resistance of antibacterial effect, inclusion complex containing cotton fabrics were repeatedly washed and tested up to 50 washes. It was determined that cotton fabrics loaded with Ag-CC:β-CD 1:2 inclusion complexes showed antimicrobial efficiency against S. aureus, B. subtilis and P. aeruginosa even after 50 washings.

Synthesis and Characterization of Inclusion Complex of Diminazene Aceturate with b-Ciclodextrin

Cyclodextrins (CD) are macrocyclic biopolymers with potential applications in the delivery of small and macro-molecular therapeutic agents. Despite the potent host-guest inclusion property, their inherent lack of cellular binding ability has limited applications in drug delivery. Herein, we functionalized b-cyclodextrin (b-CD) with diminazene aceturate(DIMA), which are bioactive molecules, widely distributed some cells, and responsible for antiprotozoal activity. The inclusion complex of DIMA with b-CD was confirmed with textural, thermogravimetric, calorimetric, spectroscopic, and microscopic techniques. Thus, the proposed inclusion complex b-CD-DIMA system could be used as a site-specific drug delivery carrier.

Preparation and Characterization of a Flavor Compound Inclusion Complex in a Simple Experiment

Flavor plays a crucial role and is the most important aspect of foods and beverages. β-Ionone is a common flavor compound with a characteristic violet-like odor. An undergraduate flavor compounds chemistry laboratory that provides preparation and characterization of the flavor compound inclusion complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) as a host and β-ionone as a guest is reported. This simple laboratory experiment allows students to become familiar with the concepts of microencapsulation technology and flavor compound inclusion complexes by teaching students how to prepare and characterize the β-ionone–HP-β-CD inclusion complex. A glass flask with a long, graduated neck is used for fabrication of the inclusion complex, which facilitates observation the volume change of β-ionone with and without the addition of HP-β-CD. From the volume change, the β-ionone loading capacity can be calculated. The volume difference of β-ionone also provides an intuitive way for students to understand that β-ionone is encapsulated in HP-β-CD and that the water solubility of β-ionone is improved by encapsulation. This laboratory experiment also allows students to become familiar with the freeze-drying process, thermogravimetric analysis (TGA), and the application of TGA in characterization of the inclusion complex. Formation of the inclusion complex and analysis of the TGA results allow students to understand the characteristics of β-ionone release from the inclusion complex and the improved thermal stability of β-ionone.

Preparation, characterization and cytotoxic evaluation of inclusion complexes between celastrol with polyamine-modified β-cyclodextrins

Celastrol (CSL), the major constituent from traditional Chinese medicine Tripterygium wilfordii Hook, has attracted considerable interest in the medicinal society due to its multiple biological activities. However, poor solubility and obvious toxic side effect have limited its application in the pharmaceutical field. To address the problems, the inclusion complexes of mono polyamine-modified β-CD (H1) and the polyamine-brideged bis(β-CD) (H2) with CSL were prepared. The characterization of inclusion complexes was investigated by NMR, XRD FT-IR and SEM, and the binding behaviors of H1-2 with CSL were investigated by UV. The results showed that the H2 gave the binding constant (Ks) towards CSL up to 1.7 times higher than that of H1, through cooperative binding of two hydrophobic CD cavities with one guest. Remarkably, complexation with H1 and H2 improved CSL solubility in water from 0.044 mg/mL up to 2.31 and 2.68 mg/mL, respectively. The in vitro anticancer activity of H1/CSL inclusion complex was better than that of cisplatin (positive control). Meanwhile, the toxicity of CSL was slightly reduced after the formation of the inclusion complex with H1. Therefore, the complexes of CSL with H1-2 favor their use in anticancer drug formulations, broadening the field of application in clinic.

Preparation and characterization of inclusion complexes between debranched maize starches and conjugated linoleic acid

Normal and high amylose maize starches were enzymatically debranched at different degrees, and then used for the preparation of inclusion complexes with conjugated linoleic acid (CLA). The recovery yield of CLA, percent ratio of CLA in the complexes to its initial amount, was increased by debranching, reaching 65% with a debranched high amylose starch (24 h). High amylose starch was more effective in the formation of CLA complexes with greater stability and crystallinity than normal starch. Both V6I and II crystals were formed by the complexation with CLA, and more V6II crystal was formed as the debranching and complexation times increased. However, an excessive complexation reaction for 24 h at 90 °C resulted in decreasing the CLA recovery, especially when normal maize starch was used. X-ray diffraction analysis revealed that B type crystals induced by starch recrystallization were also present during the complex formation. The enzymatic debranching facilitated the formation of crystalline complexes with CLA having a high thermal stability. The enzymatic debranching of starch enhanced the formation of crystalline complexes with CLA and availability of linear starch chains to form the complexes with CLA.

Preparation and physicochemical characterization of inclusion complexes derived from phytosterols and β-cyclodextrin

Phytosterols (PS), that is vegetable sterols, are compounds widely recognized for lowering the absorption of cholesterol and decreasing cancer risk, with &amp;#946;sitosterol, stigmasterol and campesterol being the most abundant. As PS is poorly soluble in aqueous solutions, many approaches have been proposed to increase their solubility and bioavailability. &amp;#946;-cyclodextrin (&amp;#946;-CD) could be used to increase PS aqueous solubility because of its capacity to entrap a variety of hydrophobic guest molecules in its cavity. In this work, the formation of &amp;#946;-CD/PS inclusion complexes was confirmed by Differential Scanning Calorimetry (DSC), Electrospray Ionization-High Resolution Mass Spectrometry (ESIHRMS) and Fourier Transform Infrared Spectroscopy (FT-IR), while structural characteristics were determined by one- and two-dimensional Nuclear Magnetic Resonance (NMR) techniques. Results confirmed 1:1 binding stoichiometry, which suggests the total inclusion of rings and chains of the different PS. The hypothesis of folding of the lateral chains into the cavity may be supported by the multiple correlations observed in the Nuclear Overhauser Effect Spectroscopy (NOESY) and rotatingframe Nuclear Overhauser Effect Spectroscopy (ROESY) spectra.

Characterization of Inclusion Complexes between Miconazole and Different Cyclodextrin Derivatives

Abstract Objective: Miconazole, an imidazole antifungal derivative, is a very hydrophobic compound, a major drawback in obtaining topical pharmaceutical formulations with optimal bioavailability. Cyclodextrins (CDs) may increase local drug delivery by enhancing the drug release and/or permeation. The aim of the study is the characterization of inclusion complexes between miconazole and different CD derivatives. Methods: Several CD derivatives were tested in the experiments. The binary systems between miconazole and different CDs were prepared in 1:1 molar ratios by physical-mixture and kneading methods. Differential scanning calorimetry (DSC) and Fourier transformed-infrared spectroscopy (FT-IR) methods were used to characterize solid state interactions between miconazole and CDs in their binary systems. Results: The FT-IR analysis suggests the formation of a new solid phase, indicating a molecular interaction between the components. The DSC analysis sustains the hypothesis of formation of partial inclusion complexes between miconazole nitrate and CD. Conclusion: The thermic behaviour of the complexes depends both on the preparation method and the composition of the products.

Characterization and cytotoxicity of a benzocaine inclusion complex

Benzocaine (BZC), is a local anesthetic widely used in topical formulations as well as in throat pastilles. A disadvantage is that the compound presents low aqueous solubility. The present work describes the preparation and characterization of an inclusion complex between BZC and β-cyclodextrin (β-CD), followed by cytotoxicity assays. The association constant (Ka) was calculated using solubility isotherms, at different temperatures, and an HPLC procedure, at room temperature, employing a reverse phase C18 column, with a mobile phase consisting of water/acetonitrile. Ka obtained with solubility isotherms at temperatures of 25, 35, and 45 °C were 229.8, 317.1, and 520.3 M−1, respectively. Employing HPLC, Ka was 38.0 M−1. The difference in the Ka value could be explained because HPLC analyses were conducted using organic solvent, which affected the host–guest interaction. Moreover, the continuous flow could have altered the degree of association of the drug with β-CD. The BZC/CD inclusion complex was characterized using infrared spectroscopy, thermogravimetry, and X-ray diffraction. Analysis showed a good agreement with literature, suggesting that the complex was established. Cytotoxicity assays using fibroblast V79 cells showed that BZC/CD formulation was not cytotoxic, demonstrating its potential to reduce the toxicity of the anesthetic. The assays demonstrated an effective interaction between BZC and CD, and that the inclusion complex was less toxic to V79 cells than the plain BZC, turning it a good alternative to decrease its toxicity when administered to patients.

Characterization of inclusion complexes of betahistine with β-cyclodextrin and evaluation of their anti-humidity properties

The formation of inclusion complexes between betahistine (BTH) and the β-CD derivatives were investigated. The binding constant (K c ) of the BTH/β-cyclodextrin (β-CD) inclusion complex was determined to be 1400 L/mol based on UV data. The structure of the BTH/β-CD complex in aqueous solution was examined by 1H–1H rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR, and the pyridine ring and side chain moiety of the BTH molecule were found to be inserted from the secondary hydroxyl face of the β-CD. The thermal properties of the solid BTH/β-CD inclusion complexes prepared by kneading and freeze-drying methods were studied by differential scanning calorimetry, and for comparison, solid betahistine mesilate (BTHm)/β-CD inclusion complexes were similarly prepared. Humidity tests showed that the solid BTH/β-CD complexes exhibited less moisture absorption compared to the BTHm alone and BTHm/β-CD complexes.

Preparation and characterization of Trimethoprim inclusion complex with Methyl-β-Cyclodextrin and determination of its antimicrobial activity

The present study focuses on the formation and characterization of inclusion complexes between Trimethoprim (TMP), an inhibitor of bacterial dihydrofolate reductase, and cyclodextrins, namely, methyl-βeta-cyclodextrin (MBCD) and hydroxylpropyl-βeta-cyclodextrin (HBCD) in aqueous solution. MBCD was selected to prepare inclusion complexes in the solid state. These complexes were prepared by different methods: spray drying, kneading and freeze drying. Physical mixtures were prepared as reference. The prepared systems were then characterized by different techniques: Differential scanning calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR) and Scanning Electron Microscopy (SEM). The dissolution profile and the antimicrobial activity of Trimethoprim and the inclusion complexes were evaluated using the dissolution test, and the disk diffusion methodology, respectively. An increase of TMP solubility was observed in phase solubility studies. The obtained apparent stability constants (Ks) showed that MBCD formed an inclusion complex more stable with the drug than HPBCD, so it was decided to prepare inclusion complexes in solid state with MBCD. The results obtained with DSC, FTIR and SEM proved the formation of inclusion complexes in solid state. The dissolution profile and the antibacterial activity increased with the complexation process.

Preparation and Characterization of Inclusion Complexes between Cyclodextrin and Block Polyether Polysiloxanes

A amphiphilic triblock copolymer, poly(ethylene oxide) -poly(dimethylsiloxane) -poly(ethylene oxide) (PEO-PDMS-PEO) was synthesized via a simple hydrosilylation reaction, and inclusion selective rule of cyclodextrins (α–CDand γ-CD) and PEO-PDMS-PEO to form inclusion complexes were discussed in this paper. Selective inclusion's impact on the triblock copolymer( PEO-PDMS-PEO) was studied.

Preparation and Characterization of Pioglitazone Cyclodextrin Inclusion Complexes

Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., β, methyl-β and γ-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-β > β > γ-cyclodextrin. The Gibbs free energy was found to be in the order γ > methyl-β > β cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-β cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-β cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml).

An alternative cyclodextrin based formulation for oral anticancer drug exemestane: In vitro and cell culture studies

summary Exemestane (EXE) is an irreversible aromatase inactivator used for the treatment of postmenopausal breast cancer. EXE is orally active but its bioavailability is about 5% due to its low solubility in water. It is known that cyclodextrin (CD) complexation enhances oral bioavailability of poorly soluble drugs. Thus, it was aimed to design and develop cyclodextrin complexes containing EXE and prepare a novel tablet formulation to improve aqueous solubility, dissolution and in vitro permeability. Introduction Estrogen suppression is an important approach to the management of hormone-responsive cancer. Therefore, aromatase inhibition is a well-established therapeutic option in postmenopausal, hormone dependent breast cancer [1]. EXE is an orally active aromatase inactivator, which is absorbed 42% from the gastrointestinal tract and preclinical data indicated that the absolute bioavailability was about 5% due to its low solubility in water and the first pass effect through liver [2,3]. Cyclodextrins (CD) are enzymatic degradation products of starch with a hydrophilic outer surface and an apolar cavity. CDs have the ability to interact with poorly water-soluble drugs and drug candidates resulting in an increase in their apparent water solubility and dissolution rates. It is also reported that CDs show permeability enhancer effects and that they can be considered practically nontoxic upon oral administration [4]. In this study, EXE's inclusion complexes were prepared and characterized using different CD derivatives (methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD)) and different preparation techniques and consequently a new tablet formulation was developed using the inclusion complex with optimal dissolution and permeation properties. Experimental methods Phase solubility studies: 0, 5,10,15, 20, 25, 30%w/v solutions ofM-β-CD,HP-β-CD andHP-γCD, all in distilled water, were added to 25 mg EXE and magnetically stirred. 7 days after which 1 mL CD drug suspensions from each vials were filtered through 0.45 μm polycarbonate membrane filter fitted in a stainless still filter holder. The experiments were performed with three replications. The filtrates were quantitatively analysed by an HPLCmethod for EXEwhichwas validated previously [5]. The apparent stability constants (K1:1) of the complexes were calculated. Preparation of inclusion complexes: The inclusion complexes of EXE with either methyl-β-cyclodextrin (M-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) were prepared by both kneading and coprecipitation methods [6] and the molar ratio of EXE:CDs were 1:1. Physical mixtures were also prepared. Characterization of inclusion complexes: Differential scanning calorimetry (DSC), Fourier transformationinfrared spectroscopy (FTIR), Proton NMR spectrometry (H NMR), Scanning electron microscopy (SEM), and X-Ray diffractometry were used to characterize both the complexes and the physical mixtures. Preparation of tablet formulation: Since phase solubility studies, solid state characterization techniques and dissolution studies indicate that M-β-CD and kneading method show the optimumresults, a tablet formulationwas developed using EXE:M-β-CD kneaded (MBK) inclusion complex. Avicel pH 102, Sodium Starch Glycolate and Magnesium Stearate were used as tablet excipients. No solubility enhancer was added to the formulation. The tablets were prepared by direct compression method. Dissolution study of inclusion complexes and tablets: Dissolution studies for EXE, EXE complexes, EXE: M-β-CD tablets and Aromasin® tablets were carried out with six replications. The dissolution medium was 900 mL of 0.5% sodium lauryl sulphate solution (SLS) and 900 mL of distilled water at 37 °C. The difference factors (f1) and the similarity factors (f2) were calculated for tablet formulations to compare dissolution profiles. Transport/permeability studies with Caco-2 cells: Caco-2 cell culture studies were performed on EXE, EXE:CD inclusion complexes which were prepared by kneading method with both M-β-CD, HP-β-CD and HP-γ-CD. Apparent permeability coefficient (Papp:cm/s) was calculated. Statistical analysis of data was performed by Kruskal Wallis One Way Variance Analysis. Result and discussion Phase solubility studies showed that the solubility of EXE increased linearly as a function of the CD concentration, a feature of AL-type complexes. K1:1 was found to be 3722.25M-1 forM-β-CD, 3728.16M-1 for HP-β-CD and 3729.22 M-1 for HP-γ-CD. EXE's solubility with M-βCDwas found tobe 513 times better than EXE. Corresponding solubility diagrams of EXE with M-β-CD, HP-β-CD and HP-γ-CD are presented respectively in Fig. 1. Abstracts / Journal of Controlled Release 148 (2010) e74–e84 e83

Preparation and characterization of inclusion complexes containing fixolide, a synthetic musk fragrance and cyclodextrins

AHTN (7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), commercially known as fixolide or tonalide, is a synthetic fragrance widely used in replace of natural musk odor which is more expensive. It is a popular fragrance material added in the manufacturing of personal care and household products, such as perfumes, soaps, shampoos, detergents, and fabric softeners. AHTN is semivolatile and is degraded under light exposure and high temperature. This work focuses on the complexation of AHTN with cyclodextrins in the effort to stabilize the fragrance material. AHTN was complexed with β-cyclodextrin, methyl (MβCD), and hydroxypropyl (HPβCD) derivatives in the mole ratio 1:1, 1:2, and 1:3 guest:host, and the complexes formed by physical mixing, co-precipitation, kneading, and freeze-drying were analyzed by DSC and FTIR. Percent AHTN included in the complex was also determined by hexane extraction and GC analysis. It was found that no inclusion complex was formed in the physical mixture. When co-precipitation method was performed, only βCD could form inclusion complex with AHTN, while the other two derivatives could not. Using 1:2 AHTN:βCD, no free AHTN was left in the complex as evidenced by DSC and FTIR spectrum. In kneading and freeze-drying methods, complexes could be formed with all CDs tested. However, co-precipitation method with 1:2 AHTN:βCD and kneading method with 1:2 AHTN:MβCD provided the highest complex yield with highest amount of AHTN included in the complex. AHTN in the complex form was more stable against high temperature and UV exposure than its free form.

Preparation and Characterization of Quercetin and Rutin Cyclodextrin Inclusion Complexes

ABSTRACTThe objective of the present study is to prepare and characterize cyclodextrin inclusion complexes of quercetin and rutin to improve their aqueous solubility and dissolution properties. Inclusion complexes of quercetin and rutin with ß-cyclodextrin (ß-CD) and hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) were prepared by kneading and coevaporation methods. Characterization of inclusion complexes was done by phase solubility analysis and was supported by X-ray powder diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier-transform infra red spectroscopy (FT-IR) analysis. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Higher dissolution rates were observed with HP-ß-CD kneaded complexes in comparison to the products with ß-CD.

Preparation and Characterization of Inclusion Complexes between Methylated Cyclodextrins and Poly(tetrahydrofuran)

Binding properties of poly(tetrahydrofuran) (PTHF) to methylated cyclodextrins (CDs) in aqueous solutions were studied by turbidity titration and 1H NMR measurements. PTHF, which has a low solubility in water, was dissolved in water on addition of 2,6-di-O-methyl-β-CD (DM-β-CD) and DM-α-CD. 2,3,6-tri-O-methyl-β-CD (TM-β-CD) and TM-α-CD did not solubilize PTHF. When PTHF was mixed with aqueous solutions of DM-β-CD and TM-β-CD, the inclusion complexes crystallized after several days. 1,4-Butanediol (monomer model) and PTHF (Mw = 250) did not form crystalline complexes with methylated CDs. The yields of the complexes of PTHF with methylated β-CDs increased with increasing molecular weight of PTHF and reached a maximum at about Mw = 1000. The complexes were characterized by 1H NMR, solid-state 13C NMR, powder X-ray, and FT-IR measurements.