Gye-Won Lee

Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation

The purpose of the present investigation was to develop and evaluate a self-microemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.

Effect of Rheum undulatum Extract on Antioxidant Activity and Activity of Matrix Metalloproteinase-1 in Human Skin Fibroblasts

Rheum undulatum L. has been commonly used as a cure for hematemesis, dropsy, and haematuria in the Oriental medicine for a long time. The main constituents of R. undulatum are chrysophanol and emodin, which are an antioxidative substance that has an anthraquinone structure. In the present study, to develop a new anti-aging agent, we examined the antioxidant activity and the inhibitory effect of the R. undulatum extract on the synthesis of MMP-1 in UVA-irradiated human dermal fibroblasts and MMP-1 activity. The R. undulatum extract was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and superoxide radicals in the xanthine/ xanthine oxidase system by a dose-dependent manner, respectively. UVA-induced MMP-1 expression was reduced about 79.5% by 1 /ml of the R. undulatum extract and also inhibited MMP-1 activity in a dose-dependent manner. In conclusion, it was observed that the R. undulatum extract has the antioxidant activity, regulation of UVA-induced MMP-1 production, and inhibition of MMP-1 activity. Therefore, these results suggest that the R. undulatum extract can be developed as a new anti-aging component of cosmetics.

Evaluation of Stability in the Purified Wood Vinegar and Its Hair Growth Effect

Generally, it takes a long time to purify wood vinegar, and it contains toxic compounds such as tar, methanol, phenol and benzopyrene. To reduce the toxicity of wood vinegar itself, we have developed a new purification method of wood vinegar using an oxidation-cohesion reaction and distillation with an active carbon. We have investigated the physico-chemical change (pH, specific gravity, refractive index and dissolved tar), the change of amount of toxic compounds (carbonyl group, phenol, benzopyrene and residual solvents) and organic acids (formic acid (FA), acetic acid (AA), propionic acid (PA)) of the purified wood vinegar under the long term and accelerated storage conditions. Also, we have evaluated the effect of the purified wood vinegar on hair growth using an alopecia model of C57BL/6 mice. As a result, we could find out that the purified wood vinegar was stable and remained without decay under the storage conditions and benzopyrene, a carcinogenic agent, was not detected in the purified wood vinegar. After topical treatment of the purified wood vinegar solution or minoxidil (MXD) for 2 weeks to dorsal skin, the hair regrowth of the mice accelerated faster than that of the control, with no clinical signs. In conclusion, we could suggest a guideline for quality control of process to reduce the toxic compounds in wood vinegar and it might be a useful hair growth promoter in the treatment of baldness or alopecia.

Formulation Design and Evaluation of Ursolic Acid Microemulsion Delivery System for Topical Formulation

Ursolic acid (UA), a bioactive triterpene acid, has been known to increase collagen content in human skin in addition to other actions such as anti-inflammatory, skin-tumor prevention and anti-invasion. However, it is poorly soluble in water. Therefore, we firstly prepared microemulsion system with benzyl alcohol, ethanol and Cremophor EL, RH 40 and Brij 35 as surfactant in order to increase solubility of UA and then prepared microemulsion was dispersed in o/w cream base for the topical delivery of UA in an effort to improve anti-wrinkle effect. The pseudo-ternary phase diagrams were developed and various microemulsion formulations were prepared using benzyl alcohol as an oil, Cremophor EL, RH 40 and Brij 35 as a surfactant. The droplet size of microemulsions was characterized by dynamic light scattering. The accumulation of VA in the skin from topical cream was evaluated in vitro using hairless mouse skins. The mean droplet size was nm for microemulsions II with Cremophor EL. All UA creams showed pseudoplastic flow and hysterisis loop in their rheogram, depending on the type of materials added in topical creams. The in vitro accumulation data demonstrated the UA topical cream prepared with the combination of Poloxamer 407 and Xanthan gum as a copolymer showed higher accumulation percentage than those prepared with either Poloxamer 407 or Xanthan gum. These results suggest that UA topical cream using microemulsion systems may be promising for the topical delivery of UA.

The effect on skin deposition and moisturizing of ursolic acid in hydrogel system containing wood vinegar

Wood vinegar is well known as a softening agent affecting on the stratum corneum that is easy to penetrate into the skin. In this study, we prepared mixed ursolic acid hydrogel with wood vinegar(1, 2, 5%) as a penetration enhancer. The accumulation of ursolic acid in the skin from hydrogels was evaluated in vitro hairless mouse skin and skin moisturizing effect of them was evaluated using the corneometer and the tewermeter. And the role of stratum corneum as a protective barrier was evaluated as well. The hydrogels were retained about 40% of water retention capacity 2hrs and had better effect on the stripped skin than full-thickness skin. The accumulation of ursolic acid through stripped skin from hydrogels with wood vinegar was not change compared to normal skin, which indicated the action site of wood vinegar and the accumulation site of ursolic acid would be stratum corneum. From these result, we could find wood vinegar seems to be a good enhancer for active materials with anti-wrinkle and anti aging effect such as ursolic acid, and can be a developed topical delivery system maintaining excellent water retention capacity.

Formulation Design and Evaluation of Niosome Containing Itraconazole for Dermal Delivery System

Itraconazole is a triazole antifungal agent to inhibit most fungal pathogens. However, it is difficult for itraconazloe to be delivered by topical system due to its poor aqueous solubility. First, niosomes containing drug were prepared with span 60, cholesterol. tocopherol and poloxamer 407 as vesicle forming agents in an effort to increase solubility of itraconazole. And then prepared niosomes were dispersed in O/W creams (containing xanthan gum, glycerin, vaseline, glyceryl monostearate and ) or gels (containing xanthan gum and poloxamer 407). Both creams and gels were evaluated with respect to their rheological properties, in vitro permeation through excised skin of hairless mouse. Creams or gels containing niosome showed pseudoplastic flow and hysteresis loop. For both creams and gels, viscosity was increased with increasing the content of glycerine or vaseline and the content of gel forming polymer, respectively. In creams, the permeability of drug to skin was decreased with increasing the viscosity of cream. The permeability of drug was affected by pH as well as viscosity of gel. In vitro permeation test results demonstrated that cream formulations showed better permeability than gels. In conclusion, these results suggest that creams formulation containing niosome can be useful for the topical delivery of intraconazole.

Formulation Design and Evaluation of Ketorolac Tromethamine Hydrogel for Transdermal Delivery System

Ketorolac tromethamine(KT) is a nonsteroidal agent with potent analgesic and moderate anti-inflammatory activity. The lipid-water partition coefficient of KT was evaluated and KT gel was formulated as a gel containing different pH, different concentrations of polymer (poloxamer 407, carbopol 941), propylene glycol, ethanol and various enhancers. The resulting KT gels were evaluated with respect to their viscosity, in vitro drug permeation rate through hairless mouse skin and stability. In n-octanol and chloroform, the lipid-water partition coefficient of KT was the highest at pH 4 phosphate buffer. The apparent viscosity of KT gel increased with an increase in gel pH, polymer and enhancer concentration. But the apparent viscosity of KT gel decreased with an increase in ethanol concentration. The permeation rate of KT through hairless mouse skin from gels different pH was maximum at pH 4 which is close to KT 3.54. The permeation rate decreased with an increase in polymer, propylene glycol concentration. But the permeation rate increased with an increase in ethanol. The increase of drug concentration from 1 to 3% induced linear increase in permeation rate. The best enhancer was the combination of , oleic acid and l-menthol. In the accelerated stability test(25, 40 and ), pH 5 gel was most stable and pH 4 gel was most unstable for 90 days.

Preparation and Evaluation of Titrated Extract of Centella Asiatica Niosome/W/O System Cream for Site Specific Targeting

For preventing and curing the stretching mark, TECA Niosome/W/O system creams were formulated using Titrated Extract of Centella Asiatica (TECA) which is well known for its excellent wound healing effect. The lipid-water partition coefficients and the stabilities of TECA were evaluated and TECA Niosome/W/O system (TECA N/W/O) creams were prepared with different concentrations of cetyl alcohol and ceramide. TECA N/W/O cream was evaluated with respect to their rheological properties, permeation through excised skin of hairless mouse and in vitro and in vivo accumulation in the skin of hairless mouse. In addition, dermal thicknesses of hairless mouse skins were determined following the in vivo application of TECA N/W/O cream and control cream. TECA N/W/O creams showed pseudoplastic flow and hysteresis loop. The permeation of TECA from formulations through excised skin of hairless mouse did not observed. Amount of accumulated drug in the excised skin of hairless mouse was deσeased with an increase in the concentration of cetyl alcohol and showed no relationship with concentration of ceramide. Amount of accumulated drug in formulation A-3 was higher than in niosome suspension and other formulations. In in vivo experiment, amount of accumulated drug in formulation A-2 and A-3 was much higher than that of niosome suspension. Being treated with the N/W/O cream for 8 weeks, the dermal thickness of hairless mouse skin was increased 3.2 times than that of 16 weeks-control group.

Preparation and Dissolution Profiles of Controled Release Formulations Containing Tamsulosin Hydrochloride

As a selective antagonist, tamsulosin has been used clinically for urinary obstructed patients with benign prostatic hyperplasia. The single and multi-layered pellets containing tamsulosin hydrochloride were prepared in an effort to control the drug release, avoiding dose-dependent side effects of tamsulosin hydrochloride upon oral administration. The drug release from multi-layered pellets was substantially controlled, compared with single layered pellets. The drug release from coated pellets with single or multi layer was affected by the nature of coating agent, the percentage of coating level and the presence of hydrophilic material in coating layer. In conclusion, the controlled release oral delivery system using multi-layered pellet is very useful for tamsulosin hydrochloride, resulting in improvement of patient compliance and therapeutic drug levels for a longer period of time.

Formulation Design of Sustained-Release Matrix Tablets Containing 4-Aminopyridine

4-Aminopyridine (AP) is a potassium channel blocker used in the treatment of neurological disorders such as multiple sclerosis and Alzheimer disease. AP‘s window of therapeutic effect appears to correlate with its plasma halflife (3.5 hours). It demonstrates pH-dependent solubility because of a weakly basic drug. In addition, the resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study is to design sustained release matrix tablet containing AP, overcoming this problem. L 100 (EuL) and sodium alginate were used in an effort to achieve pH independent drug release. The effect of sodium alginate and EuL on drug release from matrix tablet was investigated. The drug release behavior from the different tablets was analyzed by , The exponential diffusion coefficient n, kinetic constant K were calculated according to the Korsmeyer-Peppas equation. The drug release from matrix tablets prepared with sodium alginate was decreased with increasing the content of sodium alginate in pH 7.4 while there is no significant difference in pH 1.2. The exponent n values were determined to be approximately 0.5 and 0.8 respectively, in both pH 1.2 and 7.4. These values indicate diffusion-based anomalous mechanism and erosion-based anomalous mechanism, respectively. The drug release from sodium alginate matrix tablets prepared with solid dispersion of EuL containing drug showed a slow drug release in an acidic medium and a more fast drug release in phosphate medium, compared with sodium alginate matrix tablets prepared with physical mixture. These results may be attributed to the gel forming ability of sodium alginate and pH dependent solubility of EuL. Therefore, sustained-release AP matrix tablets using sodium alginate and EuL were successfully prepared.