Search Results (10)

Fenofibrate is used to treat dyslipidemia, a health condition that could lead to cardiovascular diseases. Fenofibrate is classified as a class II drug by the Biopharmaceutical Classification System due to its high lipophilicity and low solubility in water. The purpose of this work was to enhance the dissolution characteristics of fenofibrate by incorporating it into 2-hydroxylpropyl-β-cyclodextrin fibers for the first time. Single-needle electrospinning was used to prepare the fenofibrate-loaded cyclodextrin fibers. The drug loading was optimized to fulfill the electrospinning conditions and was determined to be a 1:4 drug:cyclodextrin molar ratio. We found dimethylformamide a suitable solvent and were able to prepare bead-free fenofibrate-loaded 2-hydroxylpropyl-β-cyclodextrin fibers with an average diameter of 2.65 ± 0.82 μm. Drug loading was determined to be close to the theoretical value, 97.2%, with the aid of ultraviolet spectroscopy. Differential scanning calorimetry and Fourier transform infrared spectroscopy were used to track the crystalline to amorphous transition of fenofibrate through fiber formation. The dissolution results indicated a 60-fold increase in fenofibrate from the prepared fibers with respect to the micronized active ingredient. Full article

In aqueous and solid media, 2-HP-β/γ-CD inclusion complexes with poly aromatic hydrocarbon (PAH) Phenanthrene (PHN), Anthracene (ANT), Benz(a)pyrene (BaP), and Fluoranthene (FLT) were investigated for the first time. The inclusion complexes were characterized and investigated using fluorescence and ¹HNMR spectroscopy. The most prevalent complexes consisting of both guests and hosts were those with a 1:1 guest-to-host ratio. The stability constants for the complexes of PHN with 2-HP-β-CD and 2-HP-γ-CD were 85 ± 12 M⁻¹ and 49 ± 29 M⁻¹, respectively. Moreover, the stability constants were found to be 502 ± 46 M⁻¹ and 289 ± 44 M⁻¹ for the complexes of ANT with both hosts. The stability constants for the complexes of BaP with 2-HP-β-CD and 2-HP-γ-CD were (1.5 ± 0.02) × 10³ M⁻¹ and (9.41 ± 0.03) × 10³ M⁻¹, respectively. The stability constant for the complexes of FLT with 2-HP-β-CD was (1.06 ± 0.06) × 10³ M⁻¹. However, FLT was observed to form a weak complex with 2-HP-γ-CD. Molecular dynamic (MD) simulations were used to investigate the mechanism and mode of inclusion processes, and to monitor the atomic-level stability of these complexes. The analysis of MD trajectories demonstrated that all guests formed stable inclusion complexes with both hosts throughout the duration of the simulation time, confirming the experimental findings. However, the flexible Hydroxypropyl arms prevented the PAHs from being encapsulated within the cavity; however, a stable exclusion complex was observed. The main forces that influenced the complexation included van der Waals interactions, hydrophobic forces, and C–H⋯π interaction, which contribute to the stability of these complexes. Full article

Hickory (Carya cathayensis Sarg.) oil is a nutrient-dense edible woody oil, with its unsaturated fatty acids accounting for more than 90% of total ones, and liable to oxidation spoilage. To efficiently improve its stability and expand its application fields, the microencapsulation of cold-pressed hickory oil (CHO) by the molecular embedding method and freeze-drying technique was performed using malt dextrin (MD), hydroxylpropyl-β-cyclodextrin (HP-β-CD), β-cyclodextrin (β-CD), or porous starch (PS) as a wall material. Two wall materials and/or their CHO microcapsulates (CHOM) with higher encapsulation efficiencies (EE) were selected to carry out physical and chemical characterizations using laser particle size diffractometer, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, derivative thermogravimetry, and oxidative stability tests. Results indicated β-CDCHOM and PSCHOM had significantly higher EE values (80.40% and 75.52%) than MDCHOM and HP-β-CDCHOM (39.36% and 48.32%). The particle sizes of the two microcapsules selected were both widely distributed with their spans being more than 1 µm and a certain degree of polydispersity. Microstructural and chemical characterizations indicated that β-CDCHOM had comparatively stable structure and good thermal stability compared with PSCHOM. Storage performances under light, oxygen, and temperature showed that β-CDCHOM was superior to PSCHOM, especially in terms of thermal and oxidative stability. This study demonstrates that β-CD embedding can be applied to improve the oxidative stability of vegetable oils such as hickory oil and act as a means of preparing functional supplementary material. Full article

Helichrysum italicum is a plant traditionally used for skin-related disorders that is becoming an increasingly popular ingredient in cosmetic products. In this work, a “green” ultrasound-assisted extraction method for H. italicum phenolics was developed using skin-friendly cyclodextrins (CDs). Extraction conditions needed for the greatest yield of target compounds (total phenolics, phenolic acids, and flavonoids) were calculated. The composition of the extracts was determined using LC-MS and spectrophotometric methods. Among the tested CDs, 2-hydroxylpropyl-beta-CD (HP-β-CD) was the best suited for extraction of target phenolics and used to prepare two optimized extracts, OPT 1 (the extract with the highest phenolic acid content) and OPT 2 (the extract with the highest total phenol and flavonoid content). The extracts were prepared at 80 °C, using 0.089 g of plant material/g solvent (0.6 mmol of HP-β-CD), with or without addition of 1.95% (w/w) lactic acid. The main metabolite in both extracts was 3,5-O-dicaffeoylquinic acid. It was found that the addition of lactic acid greatly contributes to the extraction of arzanol, a well-known anti-inflammatory agent. IC₅₀ values of the anti-elastase (22.360 ± 0.125 μL extract/mL and 20.067 ± 0.975 for OPT-1 and OPT-2, respectively) and anti-collagenase (12.035 ± 1.029 μL extract/mL and 14.392 ± 0.705 μL extract/mL for OPT-1 and OPT-2, respectively) activities of the extracts surpassed those of the applied positive controls, namely ursolic and gallic acids. This activity deems the prepared extracts promising ingredients for natural cosmetics, appropriate for direct use in cosmetic products, removing the need for the evaporation of conventional solvents. Full article

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. Full article

Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M⁻¹) and 2,6Me-β-CD (770 M⁻¹). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies. Full article

Due to the growing demand for patient-friendly subcutaneous dosage forms, the ability to increasing protein solubility and stability in formulations to deliver on the required high protein concentrations is crucial. A common approach to ensure protein solubility and stability in high concentration protein formulations is the addition of excipients such as sugars, amino acids, surfactants, approved by the Food and Drug Administration. In a best-case scenario, these excipients fulfil multiple demands simultaneously, such as increasing long-term stability of the formulation, reducing protein adsorption on surfaces/interfaces, and stabilizing the protein against thermal or mechanical stress. 2-Hydroxylpropyl-β-cyclodextrin (derivative of β-cyclodextrin) holds this potential, but has not yet been sufficiently investigated for use in protein formulations. Within this work, we have systematically investigated the relevant molecular interactions to identify the potential of Kleptose^®HPB (2-hydroxylpropyl-β-cyclodextrin from Roquette Freres, Lestrem, France) as “multirole” excipient within liquid protein formulations. Based on our results three factors determine the influence of Kleptose^®HPB on protein formulation stability: (1) concentration of Kleptose^®HPB, (2) protein type and protein concentration, and (3) quality of the protein formulation. Our results not only contribute to the understanding of the relevant interactions but also enable the target-oriented use of Kleptose^®HPB within formulation design. Full article

Consumers demand the use of eco-friendly fungicides to treat fruit and vegetables and governmental authorities have unauthorized the application of chemical antifungals for the efficient control of sour rot. In the present research, the microwave irradiation (MW) method was used to encapsulate thymol into 2-hydroxylpropyl-beta-cyclodextrin (HP-β-CD) and the effect of these HP-β-CD on controlling sour rot in citrus fruit, caused by Geotrichum citri-aurantii, was evaluated. Amounts of 25 and 50 mM of HP-β-CD-thymol were used, and compared with propiconazole, to control the decay of inoculated lemon fruit. The treatments were performed in curative and preventive experiments. The incidence and severity of Geotrichum citri-aurantii in 25 and 50 mM HP-β-CD-thymol-treated fruit were reduced in both experiments. The preventive 50 mM HP-β-CD-thymol treatment showed the best effect, reducing the sour rot, respiration rate and fruit weight loss during storage at 20 °C. HP-β-CD-thymol increased polyphenol concentration and the activity of antioxidant enzymes, such as catalase (CAT), ascorbate peroxidase (APX) and peroxidase (POD) in lemon peel, and the highest effects were found with the 50-mM dose. In conclusion, the results show that the use of thymol encapsulated by MW into HP-β-CD could be an effective and sustainable tool, a substitute to the synthetic fungicides, for G. citri-auriantii control in citrus fruit. Full article

The objective of this study was to elucidate the effects of hydroxylpropyl-β-cyclodextrin (HP-β-CD) on the in vitro stability of insulin. It was found that HP-β-CD had positive effects on the stability of insulin in acid and base and under high temperature conditions. Furthermore, use of HP-β-CD could also increase the stability of disulfide bonds which are important to the conformation of insulin. Through ¹H-NMR experiments it was found that the protective effect of HP-β-CD was due to complexation with insulin. The results suggest that the presence of HP-β-CD could improve the stability of insulin in different environments. Full article

Influence of pH, buffer, preservative, tonicity and viscosity modifiers on in vitrotranscorneal permeation of ofloxacin was studied using excised goat cornea. Permeation studies were carried out by putting 1 ml of test formulation on the cornea (0.78cm²) mounted between the donor and receptor compartments of an all glass modified Franz diffusion cell and measuring ofloxacin concentration in the receptor (containing bicarbonate ringer under stirring at 35°C) by spectrophotometry at 288 nm, at various time intervals up to 120 min. Buffering the formulation with phosphate buffer or use of combination of methyl and propyl paraben or benzalkonium chloride or combination of benzalkonium chloride and disodium edetate as preservative provided significant increase in the apparent corneal permeability coefficient of ofloxacin. While the use of phenyl mercuric acetate as preservative or tonicity adjustment with mannitol showed a significant decrease in apparent corneal permeability of ofloxacin. Raising the pH of test formulation from 6.4 to 7.2 or addition of hydroxyl-propyl-β-cyclodextrin or use of viscosity modifier had no significant effect on apparent corneal permeability of drug. Full article