Presence Of HPβCD Research Articles

Hydroxypropyl-β-Cyclodextrin for Delivery of Sinapic Acid via Inclusion Complex Prepared by Solvent Evaporation Method

The goal of this study was to increase the aqueous solubility and dissolution rate of sinapic acid (SA) by formulating binary inclusion complex (BIC) of SA with hydroxypropyl-β-cyclodextrin (HPβCD) using solvent evaporation (SE) technology. The phase solubility and dissolution studies were conducted to determine the solubility and in vitro release rate of SA. In addition, the prepared inclusion complex was characterized for solid state characterization using techniques such as DSC, PXRD, SEM, and FTIR. Moreover, the prepared SA-BIC was evaluated for its antioxidant activity. Results revealed that the SA solubility can be shown to improve with a change in HPβCD concentration. About 2.59 times higher solubility of SA in water was noticed in the presence of HPβCD (10 mM). Dissolution study demonstrated that the 34.11 ± 4.51% of SA was released from binary physical mixture (BPM), while the maximum release of 46.27 ± 2.79% of SA was observed for SA-BIC prepared by SE method. The prepared SA-BIC demonstrated distinctive properties when compared to pure SA, which was demonstrated by different analytical methods, such as DSC, PXRD, SEM, and FTIR, as evidence of SA inclusion into HPβCD cavity. Further, it was observed that SA-BIC displayed stronger DPPH radical scavenging activity than SA. In conclusion, SE technology considerably enhanced the complexity of SA with HPβCD, and these observations could help to heighten the SA solubility, which may lead to a better bioavailability.

Polysorbates versus Hydroxypropyl Beta-Cyclodextrin (HPβCD): Comparative Study on Excipient Stability and Stabilization Benefits on Monoclonal Antibodies.

Polysorbates (PS 20 and PS 80) are the most widely used surfactants in biopharmaceutical formulations to protect proteins from denaturation, aggregation, and surface adsorption. To date, around 70% of marketed therapeutic antibodies contain either PS 20 or PS 80 in their formulations. However, polysorbates are chemically diverse mixtures, which are prone to degradation by oxidation and hydrolysis to produce peroxides and fatty acids, which, in turn, induce protein oxidation, aggregation, and insoluble particle formation. These will negatively impact protein quality and stability. Thus, polysorbate degradation has emerged as one of the major challenges in the development and commercialization of therapeutic protein products. KLEPTOSE® HPβCD (hydroxypropyl beta-cyclodextrin), a new multifunctional excipient, has been shown to provide protein stabilization functions in biopharmaceutical downstream processes and in their final formulations. This study aims to evaluate HPβCD, a new molecule of its class, against polysorbates as a stabilizer in biologics formulations. In this study, the chemical stability of KLEPTOSE® HPβCDs is compared with polysorbates (20 and 80) under various stress conditions. When subjected to heat stress, HPβCDs show little change in product recovery (90.7–100.7% recovery for different HPβCDs), while polysorbates 20 and 80 show significant degradation, with only 11.5% and 7.3% undegraded product remaining, respectively. When subjected to other chemical stressors, namely, autoclave, light, and oxidative stresses, HPβCD remains almost stable, while polysorbates show more severe degradation, with 95.5% to 98.8% remaining for polysorbate 20 and 85.5% to 97.4% remaining for polysorbate 80. Further, profiling characterization and degradation analysis reveal that chemical structures of HPβCDs remain intact, while polysorbates undergo significant hydrolytic degradation and oxidation. Lastly, the physicochemical stability of monoclonal antibodies in formulations is investigated. When subjected to light stress, adalimumab, as a model mAb, formulated in the presence of HPβCD, shows a significant decrease in protein aggregation, and superior monomer and total protein recovery compared to PS 80-containing formulations. HPβCD also reduces both agitation and thermal stress-induced protein aggregation and prevents subvisible particle formation compared to PS 80.

Inclusion complex of clausenidin with hydroxypropyl-β-cyclodextrin: Improved physicochemical properties and anti-colon cancer activity

The long-term objective of the present study was to prepare, physicochemically characterize and determine the anticancer of clausenidin/hydroxypropyl-β-cyclodextrin (Clu/HPβCD) inclusion complex. We used differential scanning calorimetry, X-ray diffractometer, fourier transform infrared spectroscopy, ultraviolet–visible spectrophotometer and 13C and 1H nuclear magnetic resonance followed by in vitro anticancer assays. The orientation and intermolecular interactions of Clausenidin within cyclodextrin cavity were also ascertained by molecular docking simulation accomplished by AutoDock Vina. The guest molecule was welcomed by the hydrophobic cavity of the host molecule and sustained by hydrogen bond between host/guest molecules. The constant drug release with time, and increased solubility were found after successful complexation with HPβCD as confirmed by physicochemical characterizations. Clausenidin had greater cytotoxic effect on colon cancer HT29 cells when incorporated into HPβCD cavity than dissolved in DMSO. Also, from a comparison of cell viability between normal and cancer cells, a reduced side effect was observed. The Clu/HPβCD inclusion complex triggered reactive oxygen species-mediated cytotoxicity in HT29 cells. The inclusion complex-treated HT29 cells showed cell cycle arrest and death by apoptosis associated with caspases activation. The presence of HPβCD seems to aid the anticancer activity of clausenidin.

Combined Approach of Cyclodextrin Complexationand Nanostructured Lipid Carriers for the Development of a Pediatric Liquid Oral Dosage Form of Hydrochlorothiazide.

The development of specific and age-appropriate pediatric formulations is essential to assure that all children and their care-givers can easily access to safe and effective dosage forms. The need for developing specific pediatric medicinal products has been highlighted by the European Medicines Agency. The aim of this study was to investigate the effectiveness of combining the advantages of both cyclodextrin (CD) complexation and loading into nanostructured lipid carriers (NLC), to obtain a liquid oral pediatric formulation of hydrochlorothiazide (HCT), endowed with safety, dosage accuracy, good stability and therapeutic efficacy. Equimolar drug combinations as physical mixture (P.M.) or coground product (GR) with hydroxypropyl-β-cyclodextrin (HPβCD) or sulfobutylether-β-cyclodextrin (SBEβCD) were loaded into NLC, then characterized for particle size, homogeneity, Zeta potential, entrapment efficiency, gastric and storage stability. The presence of HPβCD allowed higher entrapment efficacy than NLC loaded with the plain drug, and enabled, in the case of GR systems a complete and sustained drug release, attributable to the wetting and solubilising properties of HPβCD toward HCT. In vivo studies on rats proved the superior therapeutic effectiveness of HCT-in HPβCD-in NLC formulations compared to the corresponding free HCT-loaded NLC, thus confirming the successfulness of the proposed approach in the development of an efficacious liquid oral formulation of the drug.

Pterostilbene reduces oxidative stress, prevents hypertrophy and preserves systolic function of right ventricle in cor pulmonale model.

In cor pulmonale, the increased afterload imposed on the right ventricle (RV) generates a maladaptive response, impairing the contractile cardiac function. Oxidative mechanisms play an important role in the pathophysiology and progression of this disease. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, may represent a therapeutic option. In the present study, we evaluated the effect of PTS complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on hypertrophy, contractile function and oxidative parameters in the RV of rats with pulmonary hypertension, induced by the administration of monocrotaline (MCT). The rats received daily doses of the PTS:HPβCD complex at 25, 50 or 100mg·kg-1 , p.o., for 14days. The diastolic function, E/A ratio, and systolic function, shortening fraction, fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) of the RV were determined by echocardiography. The PTS:HPβCD complex reduced the production of NADPH oxidase-dependent superoxide anions and oxidative stress in the RV of MCT-treated rats in a dose-dependent manner. At higher doses it prevented the reduction in FAC and TAPSE in MCT-treated animals. The PTS:HPβCD complex prevented the maladaptative remodelling and protected systolic function in the RV of rats with pulmonary hypertension. These cardioprotective mechanisms may be related, in part, to the antioxidant potential of PTS, favoured by the increased p.o. bioavailability promoted by the presence of HPβCD in the complex.

Cytoprotection of pancreatic β-cells and hypoglycemic effect of 2-hydroxypropyl-β-cyclodextrin: sertraline complex in alloxan-induced diabetic rats

Sertraline, a selective inhibitor of serotonin reuptake, is widely used as antidepressant in diabetic patients for improvement of depression and glycemic control. Sertraline is poorly soluble in water, which limits its oral applicability. In this work we tried to improve the pharmaceutical properties of sertraline by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and evaluated the efficacy of the HPβCD:sertraline complex in prevention of alloxan-induced lesions in rats. The solubility of sertraline increased in the presence of HPβCD and the association constant for sertraline and HPβCD was equal to 4000 ± 1000 M−1.Two-week treatment of diabetic animals with the HPβCD:sertraline complex improved pancreatic islet morphology and β-cell survival, which, in turn, reduced the severity of diabetes, as evidenced by lowering of blood glucose and glycated hemoglobin contents as well as normalization of serum insulin level and insulin sensitivity (HOMA-IR). The effect of the HPβCD:sertraline complex was strongly expressed in comparison with the antidiabetic effect of both the monopreparations, HPβCD and sertraline. It is suggested that the cyclodextrin derivative increased the pharmacological effect of sertraline, probably due to enhanced drug bioavailability.

Potential interaction between zinc ions and a cyclodextrin-based diclofenac formulation

Complexes of diclofenac sodium (DF-Na) with hydroxypropyl betacyclodextrin (HPβCD) were prepared by co-evaporation in a 1:1 ratio and characterized in light of previously reported data. Phase solubility diagrams were obtained for DF-Na with HPβCD in the presence and absence of zinc ions. Dissolution profiles were obtained for DF-Na and its HPβCD complex at acidic (pH 1.2) as well as in phosphate buffer (pH 6.8), in the presence and absence of zinc. HPβCD, as expected, was shown to improve the dissolution of DF-Na in acidic medium but not in phosphate buffer (pH 6.8). The presence of zinc ions decreased the in vitro dissolution of DF-HPβCD complex in acidic medium (pH 1.2) but not in phosphate buffer (pH 6.8). It was confirmed that the precipitate that was formed by zinc ions in the presence of HPβCD and DF-Na contained no cyclodextrin and most likely it was a mixture of the complexes: DF2-Zn and DF-Zn with some molecules of water. In vivo experiments on rats have shown that HPβCD has no statistically significant effect on absorption or bioavailability of DF-Na in spite of the observed improvement of its in vitro dissolution by HPβCD. Moreover, zinc ions were shown to decrease the absorption rate of DF-Na in rats model but did neither significantly alter the absorption nor bioavailability of DF-HPβCD complex. The zinc induced precipitates of DF were shown to have significantly different crystalline properties when HPβCD was present. Therefore, the pharmaceutical details of a DF-Na preparation should be considered when designing the formulation and predicting possible interaction between DF-Na (or other potential NSAIDs) and zinc metal.

A 5,7-dimethoxyflavone/hydroxypropyl-β-cyclodextrin inclusion complex with anti-butyrylcholinesterase activity.

This study aimed to improve the water solubility of 5,7-dimethoxyflavone (5,7-DMF) isolated from Kaempferia parviflora by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβ-CD). The phase solubility profile of 5,7-DMF in the presence of HPβ-CD was classified as AL-type and indicated a 1:1 mole ratio. Differential scanning colorimetry, X-ray diffraction, NMR and SEM analyses supported the formation of a 5,7-DMF/HPβ-CD inclusion complex involving the A ring of 5,7-DMF inside the HPβ-CD cavity. This is the first example of CD inclusion with the A ring of non-hydroxyl flavones. The stability and binding constants of the complexes were determined using the phase solubility and UV-vis absorption spectroscopy, respectively. The water solubility of 5,7-DMF was increased 361.8-fold by complexation with HPβ-CD and overcame the precipitation problem observed in aqueous buffers, such as during in vitro anti-butyrylcholinesterase activity assays. The 1:1 mole ratio of the 5,7-DMF/HPβ-CD complex showed a 2.7-fold higher butyrylcholinesterase inhibitory activity (in terms of the IC50 value) compared to the non-complexed compound.

2-Hydroxypropyl-β-cyclodextrin Promotes Transcription Factor EB-mediated Activation of Autophagy

2-Hydroxypropyl-β-cyclodextrin (HPβCD) is a Food and Drug Administration-approved excipient used to improve the stability and bioavailability of drugs. Despite its wide use as a drug delivery vehicle and the recent approval of a clinical trial to evaluate its potential for the treatment of a cholesterol storage disorder, the cellular pathways involved in the adaptive response that is activated upon exposure to HPβCD are still poorly defined. Here, we show that cell treatment with HPβCD results in the activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and in enhancement of the cellular autophagic clearance capacity. HPβCD administration promotes transcription factor EB-mediated clearance of proteolipid aggregates that accumulate due to inefficient activity of the lysosome-autophagy system in cells derived from a patient with a lysosomal storage disorder. Interestingly, HPβCD-mediated activation of autophagy was found not to be associated with activation of apoptotic pathways. This study provides a mechanistic understanding of the cellular response to HPβCD treatment, which will inform the development of safe HPβCD-based therapeutic modalities and may enable engineering HPβCD as a platform technology to reduce the accumulation of lysosomal storage material.

Oral Delivery of Lipophilic Drugs: The Tradeoff between Solubility Increase and Permeability Decrease When Using Cyclodextrin-Based Formulations

The purpose of this study was to investigate the impact of oral cyclodextrin-based formulation on both the apparent solubility and intestinal permeability of lipophilic drugs. The apparent solubility of the lipophilic drug dexamethasone was measured in the presence of various HPβCD levels. The drug’s permeability was measured in the absence vs. presence of HPβCD in the rat intestinal perfusion model, and across Caco-2 cell monolayers. The role of the unstirred water layer (UWL) in dexamethasone’s absorption was studied, and a simplified mass-transport analysis was developed to describe the solubility-permeability interplay. The PAMPA permeability of dexamethasone was measured in the presence of various HPβCD levels, and the correlation with the theoretical predictions was evaluated. While the solubility of dexamethasone was greatly enhanced by the presence of HPβCD (K1∶1 = 2311 M−1), all experimental models showed that the drug’s permeability was significantly reduced following the cyclodextrin complexation. The UWL was found to have no impact on the absorption of dexamethasone. A mass transport analysis was employed to describe the solubility-permeability interplay. The model enabled excellent quantitative prediction of dexamethasone’s permeability as a function of the HPβCD level. This work demonstrates that when using cyclodextrins in solubility-enabling formulations, a tradeoff exists between solubility increase and permeability decrease that must not be overlooked. This tradeoff was found to be independent of the unstirred water layer. The transport model presented here can aid in striking the appropriate solubility-permeability balance in order to achieve optimal overall absorption.

Weak antibody–cyclodextrin interactions determined by quartz crystal microbalance and dynamic/static light scattering

In a quest to elucidate the mechanism by which hydroxypropyl β-cyclodextrin (HPβCD) stabilizes antibodies against shaking stress, two heavily debated hypotheses exist, namely that stabilization is due to HPβCD’s surface activity, or due to specific interactions with proteins. In a previous study by Serno et al. (Pharm. Res. 30 (2013) 117), we could refute the first hypothesis by proving that, although HPβCD is slightly surface active, it does not displace the antibody at the air–water interface, and accordingly, its surface activity is not the underlying stabilizing mechanism. In the present study, we investigated the possibility of interactions between HPβCD and monoclonal antibodies as the potential stabilization mechanism using quartz crystal microbalance (QCM) and static as well as dynamic light scattering. In the presence of HPβCD, the adsorption of IgG antibodies in the native state (IgG A) and the unfolded state (IgG A and IgG B) on gold-coated quartz crystals was studied by QCM. Results show that HPβCD causes a reduction in protein adsorption in both the folded and the unfolded states, probably due to an interaction between the protein and the cyclodextrin, leading to a reduced hydrophobicity of the protein and consequently a lower extent of adsorption. These results were supported by investigation of the interaction between the native protein and HPβCD using static and dynamic light scattering experiments, which provide the protein–protein interaction parameters, B22 and kD, respectively. Both B22 and kD showed an increase in magnitude with increasing HPβCD-concentrations, indicating a rise in net repulsive forces between the protein molecules. This is further evidence for the presence of interactions between HPβCD and the studied antibodies, since an association of HPβCD on the protein surface leads to a change in the intermolecular forces between the protein molecules. In conclusion, this study provides evidence that the previously observed stabilizing effect of HPβCD on IgG antibodies is probably due to direct interactions between the cyclodextrin and the protein.

Effects of Injectable HPβCD-Diclofenac on the Human Delayed Rectifier Potassium Channel Current In Vitro and on Proarrhythmic QTc In Vivo

BackgroundNovel formulations and administration routes of established drugs may result in higher maximum concentrations or total exposures and potentially cause previously unrecognized adverse events. ObjectiveThis study evaluated the proarrhythmic potential of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac, a novel injectable diclofenac formulation solubilized with hydroxypropyl-β-cyclodextrin (HPβCD), on ventricular electrical conduction in preclinical and clinical models. MethodsWe assessed the effects of diclofenac, HPβCD, and HPβCD-diclofenac on the human delayed rectifier potassium channel (IKr) using human embryonic kidney (HEK) 293 cells transfected with a human ether-à-go-go–related gene (hERG) using whole-cell patch-clamp. In a single-dose, active- and placebo-controlled, 4-period crossover, thorough QT in vivo study, 70 healthy volunteers (mean age, 23.3 years; range, 18–49 years; 55.75% male) received HPβCD-diclofenac at 37.5- and 75-mg doses, inactive vehicle (placebo), and an active control (moxifloxacin). ResultsIn vitro, diclofenac produced no statistically significant effect on IKr. Significant, non–dose-dependent effects were observed in the presence of HPβCD or HPβCD-diclofenac of similar magnitude across the 300-fold dose range of concentrations tested, suggesting an artifact due to the detergent effect of HPβCD in this in vitro model. In vivo, neither HPβCD-diclofenac dose resulted in QTc prolongation ≥2 ms (≥5 ms is the threshold of clinical concern). No correlation was evident between changes in QTc and plasma concentrations of diclofenac or HPβCD. Confirming study sensitivity, moxifloxacin produced a mean QTc prolongation >10 ms. ConclusionsThe findings from the present study suggest that HPβCD-diclofenac does not have a dose-dependent effect in the in vitro hERG assay system and does not produce proarrhythmic QTc prolongation in vivo. ClinicalTrials.gov identifier: NCT01812538.

Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations

To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220 nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA–HPβCD systems showed an AL type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24 h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6 h incubation period, the cellular uptake was found at 33% and 32% for P–CsA and P–HPβCD–CsA nanoparticles, respectively.

Effect of Ion Pairing on In Vitro Transcorneal Permeability of a Δ9-Tetrahydrocannabinol Prodrug: Potential in Glaucoma Therapy

The aim of the present study was to evaluate and improve the in vitro transcorneal permeability characteristics of Δ(9) -tetrahydrocannabinol (THC) through prodrug derivatization and formulation approaches. In vitro corneal permeability of THC and its hemisuccinate (THC-HS) and hemiglutarate (THC-HG) ester prodrugs and WIN 55-212-2 (WIN), a synthetic cannabinoid, was determined using isolated rabbit cornea. The formulations studied included hydroxypropyl beta cyclodextrin (HPβCD) or randomly methylated beta cyclodextrin (RMβCD), as well as prodrug-ion-pair complexes with l-arginine or tromethamine. Corneal permeability of WIN was found to be two-fold higher than THC in the presence of HPβCD. THC-HS and THC-HG exhibited pH-dependent permeability. In the presence of HPβCD, at pH 5 (donor solution pH), both prodrugs exhibited six-fold higher permeability compared with THC. However, permeability of the prodrugs was about three-fold lower than that of THC at pH 7.4. RMβCD, at pH 7.4, led to a significant improvement in permeability. Formation of ion-pair complexes markedly improved the solubility and permeability of THC-HG (sevenfold and threefold greater permeability compared with THC and WIN, respectively) at pH 7.4. The in vitro results demonstrate that the use of an ion-pair complex of THC-HG could be an effective strategy for topical delivery of THC.

Complex formation of chlorhexidine gluconate with hydroxypropyl-β-cyclodextrin (HPβCD) by proton nuclear magnetic resonance spectroscopy ( 1H NMR)

The complex formation of chlorhexidine digluconate (CHX-G 2) with hydroxypropyl-β-cyclodextrin (HPβCD) was studied using NMR spectroscopy. The results revealed that this surfactant agent shows an monomer/aggregate equilibrium, which is dependent on the concentration of this drug. This equilibrium can be modified by the presence of HPβCD, which reduces the aggregation of the CHX-G 2 molecules. An inclusion process of the CHX-G 2 aromatic residue within the cyclodextrin cavity was confirmed by 2D ROESY spectroscopy. 1H NMR titration studies of CHX-G 2 with HPβCD in D 2O confirmed the formation of higher order complexes between CHX-G 2 and HPβCD. Moreover, the addition of HPβCD into CHX-G 2 solutions forms insoluble aggregates. Such insoluble aggregates may result in the stacking of CHX-G 2 molecules on the surface of the CHX-G 2:HPβCD complexes.

Use of 2-hydroxypropyl-β-cyclodextrin as adjuvant for enhancing encapsulation and release characteristics of asiaticoside within and from cellulose acetate films

The inclusion complex between asiaticoside (AC), an active substance from the medicinal plant Centella asiatica L., and 2-hydroxypropyl-β-cyclodextrin (HPβCD) was investigated. The phase solubility profiles of AC in distilled water and 90:10 (v/v) mixture of 80 vol.% acetic acid and N,N-dimethylacetamide (DMAc) both in the absence and the presence of HPβCD were classified as A L-type and indicated a 1:1 molar ratio of the AC/HPβCD complex. The 1:1 stoichiometric molar ratio of the complex was confirmed by both the 1D and the 2D 1H-nuclear magnetic resonance spectrometry. Unlike the highly crystalline nature of the native AC, the stoichiometric AC/HPβCD complex powder was amorphous in nature. The average diameters of the self-assembling aggregates of the AC/HPβCD complex, a priori prepared at various HPβCD to AC molar ratios of 0.5, 1, and 2, in the solution state, were about 2.4, 3.3, and 3.8 μm, respectively. The solvent-cast CA films containing these complexes showed strong evidence of the aggregates on their surfaces. The maximal cumulative released amounts of AC, a sparingly water-soluble substance, from the CA films containing a mixture of AC/HPβCD of varying molar ratios (i.e., 1:0.5, 1:1, and 1:2) in the phosphate buffer saline solution (PBS) containing 10% (v/v) methanol (i.e., P/B/M medium) were 2.2, 3.9, and 5.8% (based on the actual weights of the film specimens), respectively, which were clearly an increasing function of the HPβCD content in the films.

Functional Properties and Retrogradation of Heat‐Moisture Treated Wheat and Potato Starches in the Presence of Hydroxypropyl β‐cyclodextrin

AbstractSome functional and retrogradation properties of native and heat‐moisture treated potato and wheat starches were examined in the presence of hydroxypropyl β‐cyclodextrin (HPβ‐CD). HPβ‐CD increased swelling factor, amylose leaching, and solubility of both native and heat‐moisture treated wheat starches but it had less impact on corresponding potato starches. Gelatinization enthalpy of native wheat starch was decreased in the presence of HPβ‐CD but was increased in potato starch with increasing concentration. Reduction of amylose‐lipid complex endotherm in both native and heat‐moisture treated wheat starch was observed in the presence of HPβ‐CD. Heat‐moisture treatment did not change the transition parameters of amylose‐lipid complex showing its resistance to hydrothermal treatment. HPβ‐CD greatly decreased the pasting temperature of wheat starch. Cold paste viscosity of both native and heat‐moisture treated wheat starch was increased by HPβ‐CD to a greater extent than corresponding potato starch. Amylopectin retrogradation of all the starches was unaffected in the presence of HPβ‐CD but heat‐moisture treatment slightly decreased retrogradation of potato starch. These results suggest that HPβ‐CD can disrupt the amylose‐lipid complex within the starch granule in both native and heat‐moisture treated wheat starch but has no influence on amylopectin retrogradation. However, greatly increased wheat starch setback with HPβ‐CD indicates its greater effect on wheat starch amylose retrogradation.

Effects of hydroxypropyl-β-cyclodextrin, gel and in situ gelling systems on the stability of hydrocortisone after gamma irradiation

This work investigated the potential of (2-hydroxy)propyl-β-cyclodextrin (HPβCD) to protect hydrocortisone against degradation by gamma radiation. Hydrocortisone stability was monitored after irradiation of aqueous solution in absence and presence of HPβCD. The study also monitored the stability after incorporation of hydrocortisone- HPβCD solution in carboxymethylcellulose gel, alginate-based and carbopol-based in situ gelling systems. Incorporation of HPβCD in hydrocortisone aqueous solution significantly increased the drug stability after gamma irradiation. The recovered chemical potency values of the drug in presence of HPβCD were significantly higher than those recovered after irradiation of drug solution in absence of HPβCD. Irradiation of the gel or in situ gelling systems containing HPβCD-drug solution resulted in a significant reduction in the viscosity with the recovered drug concentrations being similar to those recovered in absence of the gelling system. The study indicated the potential of HPβCD to protect hydrocortisone against gamma irradiation with no augmentation from the gel or gelling systems.

Photostabilization of oxolinic acid in hydroxypropyl-β-cyclodextrins; implications for the effect of molecular self-assembly phenomena

Oxolinic acid (OXA) is a first-generation quinolone antibacterial agent, known to cause drug induced photosensitivity. In the present work its photoinduced degradation was monitored under simulated solar irradiation. The effect of photoprotecting agents on OXA stability was also assessed by drug complexation with hydroxypropyl-β-cyclodextrin (HPβCD). The complex was studied by UV-Vis and 1H (2D) NMR Spectroscopy. A photostability indicating chromatographic method was developed and validated. Because OXA is insoluble in acidic solutions, and because an acidic solvent is necessary for successful chromatographic separation, a procedure was developed to pre-treat the sample. This method is suitable for the separation of degradation products from OXA and from each other. The method was also evaluated in the presence of HPβCD, in order to ensure that inclusion complexation did not generate inaccuracies. Investigation of OXA photodegradation profiles confirms first order kinetics and acceleration at higher initial sample concentrations. A 94% photostabilization upon complexation with HPβCD was achieved. Furthermore, molecular self association phenomena were determined by self titration experiments, using 1H NMR Spectroscopy and suggestions were made for the photostabilization mechanism of cyclodextrins.

Investigation of inclusion complex of trazodone hydrochloride with hydroxypropyl-β-cyclodextrin

Inclusion complex of trazodone hydrochloride (TRD) with hydroxypropyl-β-cyclodextrin (HP-βCD) has been investigated by 1H NMR, 13CNMR, 2D NMR, FTIR and UV/visible spectroscopy. It was testified that the inclusion complex was formed between HP-βCD and trazodone. The stability constant K 1:1 and the 1:1 stoichiometry of complexation was determined. NMR analysis confirmed the inclusion and to provide information on the behaviour of TRD inside the cavity of HP-βCD. It was found that the fragment of TRD molecule, the benzene ring entered into the cavity of HP-βCD. Concerning the structure of the inclusion complex, a Cl− in orientation of trazodone in hydroxypropyl-β-cyclodextrin cavity has been confirmed by 2D NMR spectroscopy. Based on the enhancement of the absorbance of trazodone produced throught complex formation, a spectrophotometric method for the determination of trazodone in bulk aqueous solution in presence of HP-βCD was developed, which overcome the effect of condition change on the determination of trazodone. The linear relationship between the absorbance and trazodone concentration was obtained in the range of 5–30 μg ml −1 with a correlation coefficient of 0.9998. The detection limit was 0.27 μg ml −1.