Eun-Kyoung Park

Poloxamer/Cyclodextrin/Chitosan-Based Thermoreversible Gel for Intranasal Delivery of Fexofenadine Hydrochloride

To enhance permeation and solubility of an intranasal delivery system of fexofenadine hydrochloride (FXD HCl), a new formulation using poloxamer 407 (P407)/hydroxypropyl-β-cyclodextrin (HP-β-CD)-based thermoreversible gels with chitosan, was developed. Prepared gels were characterized by gelation temperature, viscosity, viscoelasticity, and drug release profile. The in vitro permeation study was performed in primary human nasal epithelial cell monolayers cultured by air-liquid interface method. The addition of chitosan caused the slight elevation of gelation temperature and viscosity-enhancing effect. Viscosity enhancement by the incorporation of chitosan caused the retardation of drug release from P407 gels in in vitro release test. The in vitro permeation profile showed that the increase in chitosan content (0.1% and 0.3%, w/v) significantly enhanced the permeation of FXD HCl. After intranasal administration of P407/HP-β-CD-based thermoreversible gels containing 0.1% and 0.3% of chitosan in rabbits at 0.5 mg/kg dose, plasma concentrations of FXD HCl were significantly higher than those of nasal solutions (p < 0.05). In particular, the bioavailability of the optimized thermoreversible gel containing 0.3% chitosan was about 18-fold higher than that of the solution type. These results suggested the feasibility that thermosensitive gels could be used as an effective dosage form to enhance the nasal absorption of FXD HCl.

Rheological evaluation of petroleum jelly as a base material in ointment and cream formulations: steady shear flow behavior.

The objective of the present study is to systematically characterize a nonlinear rheological behavior of petroleum jelly (petrolatum) in steady shear flow fields correspondent to the spreading condition onto the human body. With this aim, using a strain-controlled rheometer, the steady shear flow properties of commercially available petroleum jelly have been measured at 37°C (body temperature) over a wide range of shear rates. In this article, the shear rate dependence of steady shear flow behavior was reported from the experimentally obtained data. In particular, the existence of a yield stress and a non-Newtonian flow behavior were discussed in depth with a special emphasis on their importance in actual application onto the human body. In addition, several inelastic-viscoplastic flow models including a yield stress parameter were employed to make a quantitative description of the steady shear flow behavior, and then the applicability of these models was examined in detail. Main findings obtained from this study can be summarized as follows: (1) Petroleum jelly exhibits a finite magnitude of yield stress. The appearance of a yield stress is attributed to its three-dimensional network structure that can show a resistance to flow and plays an important role in determining a storage stability and sensory feature of the product. (2) Petroleum jelly demonstrates a pronounced non-Newtonian shear-thinning flow behavior which is well described by a power-law equation and may be interpreted by the disruption of a crystalline network under the influence of mechanical shear deformation. This rheological feature enhances sensory qualities of pharmaceutical and cosmetic products in which petroleum jelly is used as a base material during their actual usage. (3) The Casson, Mizrahi-Berk, Heinz-Casson and Herschel-Bulkley models are all applicable and have almost an equivalent ability to quatitatively describe the steady shear flow behavior of petroleum jelly whereas the Bingham model does not give a good validity. Among these flow models, the Herschel-Bulkley model provides the best applicability.

A Proton Pump Inhibitor's Effect on Bone Metabolism Mediated by Osteoclast Action in Old Age: A Prospective Randomized Study

Background/Aims Proton pump inhibitors (PPIs) act by irreversibly binding to the H+-K+-ATPase of the proton pump in parietal cells and may possibly affect the vacuolar H+-ATPase in osteoclasts. Methods We investigated the effect of 8 weeks of PPI treatment on the parameters of bone turnover and compared PPI with revaprazan, which acts by reversibly binding to H+-K+-ATPase in proton pumps. This study was a parallel randomized controlled trial. For 8 weeks, either a PPI or revaprazan was randomly assigned to patients with gastric ulcers. The parameters of bone turnover were measured at the beginning of and after the 8-week treatment period. Results Twenty-six patients (PPI, n=13; revaprazan, n=13) completed the intention-to-treat analysis. After the 8-week treatment period, serum calcium and urine deoxypyridinoline (DPD) were increased in the PPI group (serum calcium, p=0.046; urine DPD, p=0.046) but not in the revaprazan group. According to multivariate linear regression analysis, age ≥60 years was an independent predictor for the changes in serum calcium and urine DPD. Conclusions In elderly patients, administering a PPI for 8 weeks altered bone parameters. Our study suggested that PPIs might directly alter bone metabolism via the vacuolar H+-ATPase in osteoclasts.

Successful Treatment by Chemotherapy of Pineal Parenchymal Tumor with Intermediate Differentiation: A Case Report

A 37-year-old male presented with a mass measuring 2.5 cm in size in the midbrain and obstructive hydrocephalus, which had manifested as a headache and dizziness. Magnetic resonance (MR) imaging of the brain showed intermediate enhancement on T1-weighted MR imaging and a high intensity of enhancement on T2-weighted MR. Neurosurgeons performed an occipital craniotomy with partial removal of the tumor and the postoperative diagnosis was a pineal parenchymal tumor with intermediate differentiation. He had undergone irradiation with 54 Gy of radiation on 27 fractions for removal of the remaining tumor approximately one month after surgery. However, in follow-up imaging performed four months after radiotherapy, a remnant mass in the superoposterior aspect of the midbrain was found to have extended to the hypothalamus and the third ventricle. He was treated with six cycles of procarbazine, lomustine, vincristine chemotherapy. At five months since the completion of chemotherapy, the brain MR imaging showed no evidence of any remaining tumor and he no longer displayed any of his initial symptoms.

Carbopol-incorporated thermoreversible gel for intranasal drug delivery.

The present study describes the preparation and evaluation of a poloxamer 407 (P407)-based thermoreversible gel using Carbopol 934P (C934P) as a mucoadhesive polymer and hydroxypropyl-β-cyclodextrin (HP-β-CD) for enhancing the aqueous solubility and intranasal absorption of fexofenadine hydrochloride (FXD HCl). The prepared gels were characterized by gelation temperature, viscoelasticity, and drug release profile. Thermoreversibility of P407/C934P gel was demonstrated by rheological studies. The incorporation of carbopol into P407 gel also reduced the amounts of drug released from the gel formulations (p < 0.05). In vivo pharmacokinetic results of the prepared gel formulations in rabbits (at 0.5 mg/kg dose) showed that the relative bioavailability of drug from P407/C934P gel was 11.3 and 2.7-fold higher than those of drug solution and P407 gel group, respectively. These findings suggested that developed thermoreversible gels could be used as promising dosage forms to improve intranasal drug absorption.

Drug survival and the associated predictors in South Korean patients with rheumatoid arthritisreceiving tacrolimus

Background/Aims To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care. Methods2018-01-16 In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses. Results TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039). Conclusions In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

Medication nonadherence in Korean patients with rheumatoid arthritis: the importance of beliefabout medication and illness perception

Background/Aims To investigate medication nonadherence in Korean patients with rheumatoid arthritis (RA) and analyze related factors. Methods A total of 292 patients with RA participated in this study. Medication nonadherence, intentional or unintentional, was gauged via self-reported questionnaire. Patient perceptions of illness, treatment beliefs, and moods were measured via Brief Illness Perception Questionnaire, Beliefs about Medicines Questionnaire, and Patient Health Questionnaire-2, respectively. Demographic and clinical data were also collected. Multinomial regression analysis was used to assess the impact of demographic, clinical, and psychological factors on medication nonadherence. Results The medication nonadherence rate was 54.1% (intentional, 21.6%; unintentional, 32.5%). Intentional nonadherence was reported most often in patients treated daily drugs (nonsteroidal anti-inflammatory drugs and/or disease-modifying antirheumatic drugs) (24.2%), and unintentional nonadherence was highest in patients receiving methotrexate (33.3%) (p = 0.872). In univariate analysis, beliefs in necessity and concerns of medication differed significantly in adherent and nonadherent patients (intentional or unintentional). When controlling for other factors that may impact medication nonadherence, less belief in necessity of medication (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.68 to 0.95) and greater emotional response to disease (OR, 1.19; 95% CI, 1.01 to 1.40) were important predictors of intentional nonadherence. Conclusions Medication nonadherence is common in Korean patients with RA. Less belief in necessity of medication and greater emotional response to disease were identified as key factors prompting intentional nonadherence. These factors may be strategically targeted to improve medication adherence rates and subsequent clinical outcomes.

Effect of urea on heat-induced gelation of bovine serum albumin (BSA) studied by rheology and small angle neutron scattering (SANS)

This paper reports the effects of urea on the heat-induced gelation of bovine serum albumin (BSA), which was studied by the tube inversion method, rheological measurements, and small-angle neutron scattering (SANS). An increase in the urea concentration accelerated the rate of gelation because the protein molecules have already been unfolded to some extent during sample preparation in the urea solution. In addition, the BSA solution in the presence of urea underwent a sol-gel-sol transition during the time sweep test at a constant temperature of 80oC. On the other hand, the BSA solution without urea turned into a hard and brittle gel that did not return to the solution state during isothermal heating at a constant temperature of 80oC. Aggregation and re-bonding of the denatured and unfolded protein chains led to gel formation. Urea added to the protein denatures its tertiary and secondary structures by simultaneously disrupting the hydrogen bonds, hydrophobic interactions, and altering the solvent properties. Furthermore, urea induces thermoreversible chemical interactions in BSA solutions leading to the formation of a gel with dynamic properties under these experimental conditions.

Effects of the energy-separation filter on the performance of each detector layer in the sandwich detector for single-shot dual-energy imaging

A novel sandwich-style single-shot detector has been built by stacking two indirect-conversion flat-panel detectors for preclinical dual-energy mouse imaging. Although this single-shot method is more immune to motion artifacts compared with the conventional dual-shot method (i.e., fast kVp switching), it may suffer from reduced image quality because of poor spectral separation between the two detectors. Spectral separation can be improved by using an intermediate filter between the two detector layers. Adversely, the filter reduces the number of x-ray photons reaching the rear detector, hence probably increasing image noise. For a better design and practical use of the sandwich detector for single-shot dual-energy imaging, imaging performances of each detector layer in the sandwich detector are investigated for various spectral-separation extents and applied tube voltages. The imaging performances include the modulation-transfer function, the Wiener noise-power spectrum, and the detective quantum efficiency. According to the experimental results, impacts of the intermediate filter on the imaging performances of each detector layer are marginal. The detailed experimental results are shown in this study.

Rheological analysis of core-stabilized Pluronic F127 by semi-interpenetrating network (sIPN) in aqueous solution

A poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer (Pluronic F127) micelle system was stabilized using an ultraviolet-induced semi-interpenetrating network (sIPN). The sIPN structure within the micelle cores was found to stabilize the micelles against low temperatures, but affected the resulting material properties. In this study, the rheological properties of Pluronic F127 with sIPN (F127-sIPN) and without sIPN (F127) were compared. The presence of the sIPN structure increased the gelation temperature (Tgel) at the same concentration, and unlike F127, F127-sIPN exhibited strong heating rate dependent and thermodynamically irreversible behaviors. Hard gels containing various concentrations of F127-sIPN and F127 were investigated at 40 °C. At concentrations above 18 wt. %, both F127-sIPN and F127 exhibited similar linear viscoelastic properties due to the tight, ordered core–shell micelles packing, but the two systems exhibited different behaviors below 18 wt. % concentrat...