Wen-Ho Chuo

Preparation and in-vitro evaluation of nifedipine loaded albumin microspheres cross-linked by different glutaraldehyde concentrations

Nifedipine-loaded albumin microspheres were prepared by a chemical cross-linking method to develop a sustained release form. The effects of cross-linking agent (glutaraldehyde) on the percentage of drug loading, biodegradability of albumin microspheres and drug release kinetics were investigated in this study. Moreover, the kinetics of nifedipine released from different albumin microspheres were analysed using four different theoretical models, that is, zero order, first order, planar matrix and spherical matrix model. Albumin microspheres prepared with different amounts of glutaraldehyde indicated different release kinetics. Increasing the glutaraldehyde concentration decreased the release rate of nifedipine from albumin microspheres as a result of formation of greater structural strength and more tightly texture. Besides, albumin microspheres gave an adequate fit to either zero order or spherical matrix model, depending on the extent of cross-linking reaction.

Low-Energy Helium-Neon Laser Therapy Induces Repigmentation and Improves the Abnormalities of Cutaneous Microcirculation in Segmental-Type Vitiligo Lesions

Segmental vitiligo (SV) is a special form of vitiligo occurring in a dermatomal distribution, and an abnormality involving the sympathetic nerves supplying the affected dermatome is known to underlie this disorder. Previously, we have shown that SV is associated with an abnormal increase in cutaneous blood flow and adrenoceptor responses in the affected areas. Since SV is resistant to conventional forms of therapy, its management represents a challenge for dermatologists. Low energy helium‐neon lasers (He‐Ne laser, wavelength 632.8nm) have been employed as a therapeutic instrument in many clinical situations, including vitiligo management and repair of nerve injury. The purpose of this study was to evaluate the effectiveness and safety of He‐Ne lasers in treating SV, and determine their effects on the repair of sympathetic nerve dysfunction. Forty patients with stable‐stage SV on the head and/or neck were enrolled in this study. He‐Ne laser irradiation was administered locally at 3.0J/cm2 with point stimulation once or twice weekly. Cutaneous microcirculatory assessments in six SV patients were performed using a laser Doppler flowmeter. The sympathetic adrenoceptor response of cutaneous microcirculation was determined by measuring cutaneous blood flow before, during and after iontophoresis with sympathomimetic drugs (phenylephrine, clonidine and propranolol). All measurements of microcirculation obtained at SV lesions were simultaneously compared with contralateral normal skin, both before and after He‐Ne laser treatment. After an average of 17 treatment sessions, initial repigmentation was noticed in the majority of patients. Marked repigmentation (> 50%) was observed in 60% of patients with successive treatments. Cutaneous blood flow was significantly higher at SV lesions compared with contralateral skin, but this was normalized after He‐Ne laser treatment. In addition, the abnormal decrease in cutaneous blood flow in response to clonidine was improved by He‐Ne laser therapy. Our study showed that He‐Ne laser therapy is an effective treatment for SV by normalizing dysfunctions of cutaneous blood flow and adrenoceptor responses in SV patients. Thus, the beneficial effects of He‐Ne laser therapy may be mediated in part by a reparative effect on sympathetic nerve dysfunction.

Formulation Design of a Highly Hygroscopic Drug (Pyridostigmine Bromide) for its Hygroscopic Character Improvement and Investigation of In Vitro/In Vivo Dissolution Properties

ABSTRACT Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 23 full factorial design. In vitro studies, the 23 full factorial design was utilized to search for the optimal SR pellets with specific release rate at different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24, 33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism (n = 0.93). The results of moisture absorption by Karl Fischer has shown the optimum SR pellets at 25°C/60% RH, 30°C/65% RH, and 40°C/75% RH chambers from 1 hr–4 weeks, attributing that the moisture absorption was not significantly increased. In the in vivo study, the results of the bioavailability data showed the Tmax (from 0.65 ± 0.082 hr–4.82 ± 2.12 hr) and AUC0–30 hr (from 734.88 ± 230.68 ng/mL.hr–1454.86 ± 319.28 ng/mL.hr) were prolonged and increased, as well as Cmax (from 251.87 ± 27.51 ng/mL–115.08 ± 14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with commercial immediate-release (IR) tablets. Furthermore, a good linear regression relationship (r = 0.9943) was observed between the fraction dissolution and fraction absorption for the optimum SR pellets. In this study, the formulation design not only improved the hygroscopic character of PB but also achieved the SR effect.

Development of nifedipine-loaded albumin microspheres using a statistical factorial design

Nifedipine-loaded albumin microspheres were prepared by a chemical cross-linking method to develop a sustained-release form. The qualities of the nifedipine-loaded albumin microsphere products were affected by several variables. In this study, the effects on the percentage of nifedipine incorporated into albumin microspheres of four different variables (i.e. drug/albumin ratio, amount of glutaraldehyde, amount of sodium dodecyl sulfate and stirring speed) at two levels were studied according to a factorial design of experiments.

Evaluation of Era-Tab as a Direct Compression Excipient

AbstractThe physical and compressional properties of a modified rice starch, Era-Tab, were evaluated and compared with those of 4 commercially available direct compression excipients, namely, microcrystalline cellulose (Avicel PH-101), partially pregelatinized starch, spray-dried lactose (Super-Tab Lactose), and granular dicalcium phosphate dihydrate (Emcompress). It was found that Era-Tab possessed high flowability and adequate compressibility. The compacted material made with Era-Tab has a higher crushing strength and a lower friability than 3 other direct compression excipients, except microcrystalline cellulose. Tablets containing terfenadine of the same degree of hardness (10 kg) were also prepared using different direct compression excipients. The disintegration time of the tablets made with Era-Tab was approximately 2.5 min. The maximum of the accumulated percentage of terfenadine released from the tablet reached 90%, and 63.2% of it was released within 20 min. Both the powder characteristics and t...

Formulation Design of an HPMC-Based Sustained Release Tablet for Pyridostigmine Bromide as a Highly Hygroscopic Model Drug and its In Vivo/In Vitro Dissolution Properties

Pyridostigmine bromide (PB), a highly hygroscopic drug was selected as the model drug. A sustained-release (SR) tablet prepared by direct compression of wet-extruded and spheronized core pellets with HPMC excipients and exhibited a zero-order sustained release (SR) profile. The 23 full factorial design was utilized to search an optimal SR tablet formulation. This optimal formulation was followed zero-order mechanism and had specific release rate at different time intervals (released % of 1, 6, and 12 hr were 15.84, 58.56, and 93.10%). The results of moisture absorption by Karl Fischer meter showed the optimum SR tablet could improve the hygroscopic defect of the pure drug (PB). In the in vivo study, the results of the bioavailability data showed the Tmax was prolonged (from 0.65 ± 0.082 hr to 4.83 ± 1.60 hr) and AUC0–t (from 734.88 ± 230.68 ng/ml.hr to 1153.34 ± 488.08 ng/ml.hr) and was increased respectively for optimum PB-SR tablets when compared with commercial immediate release (IR) tablets. Furthermore, the percentages of in vitro dissolution and in vivo absorption in the rabbits have good correlation. We believe that PB-SR tablets designed in our study would improve defects of PB, decrease the frequency of administration and enhance the retention period of drug efficacy in vivo for personnel exposed to contamination situations in war or terrorist attacks in the future.

Effective inhibition of MERS-CoV infection by resveratrol

BackgroundMiddle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging viral pathogen that causes severe morbidity and mortality. Up to date, there is no approved or licensed vaccine or antiviral medicines can be used to treat MERS-CoV-infected patients. Here, we analyzed the antiviral activities of resveratrol, a natural compound found in grape seeds and skin and in red wine, against MERS-CoV infection.MethodsWe performed MTT and neutral red uptake assays to assess the survival rates of MERS-infected Vero E6 cells. In addition, quantitative PCR, western blotting, and immunofluorescent assays determined the intracellular viral RNA and protein expression. For viral productivity, we utilized plaque assays to confirm the antiviral properties of resveratrol against MERS-CoV.ResultsResveratrol significantly inhibited MERS-CoV infection and prolonged cellular survival after virus infection. We also found that the expression of nucleocapsid (N) protein essential for MERS-CoV replication was decreased after resveratrol treatment. Furthermore, resveratrol down-regulated the apoptosis induced by MERS-CoV in vitro. By consecutive administration of resveratrol, we were able to reduce the concentration of resveratrol while achieving inhibitory effectiveness against MERS-CoV.ConclusionIn this study, we first demonstrated that resveratrol is a potent anti-MERS agent in vitro. We perceive that resveratrol can be a potential antiviral agent against MERS-CoV infection in the near future.

Preparation and Pharmacological Evaluation of Physostigmine-Loaded Polyisobutylcyanoacrylate Nanoparticles in Rats

The nanoparticles of physostigmine were prepared by an emulsion polymerization of polyisobutylcyanoacrylate. The drug content, release and particle size distribution of the nanoparticles were characterized. In vitro drug release profiles displayed a retardation by the nanoparticles in comparison to the aqueous solution. Pharmacological evaluation of physostigmine nanoparticles in vivo were carried out with Sprague-Dawley rats. The endogenous acetylcholine was sampled by on-line microdialysis and determined by a sensitive microbore HPLC/ED system in the striatum of rats. The choline oxidase and catalase immobilized enzyme reactors were used as the pre-column to erase choline. Accordingly, this chromatographic flow sequence could be utilized for the quantitative assay of acetylcholine without interference. The results indicate that the increase of acetylcholine (%) in the rats striatum by the nanoparticle was 2.3 times (AUC) higher than that of aqueous solution.