การพัฒนาอีโธโซมของอินโดเมทาซินเพื่อการนำส่งผ่านผิวหนัง

Thesis (M.Sc.,Phamaceutical Sciences)--Prince of Songkla University, 201

Potential of Vesicles to Optimize Topically Applied Formulations with Enhanced Skin Penetration of Drugs

学位授与機関：城西大学 学位記番号：博甲第77号，学位の種別：博士（薬科学）， 学位授与年月日： 平成29年(2017年)9月20日 (61p.)博士（薬科学）城西大

Development of Oral Microemulsion Spray Containing Pentacyclic Triterpenes-Rich Centella asiatica (L.) Urb. Extract for Healing Mouth Ulcers

Several publications have shown that Centella asiatica (L.) Urb. and its active constituents (pentacyclic triterpenes) are effective in wound healing. The pentacyclic triterpenes-rich C. asiatica extract (PRE) was prepared following a previous study by microwave-assisted extraction (MAE) and fractionation with macroporous resin. This method provided the pentacyclic triterpene content in the extract up to 59.60% w/w. The PRE showed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production with an IC50 value of 20.59 ± 3.48 μg/mL and a potent fibroblast proliferative effect (165.67%) at concentrations of 10 μg/mL. The prepared microemulsion consisted of a water: oil: surfactant mixture of 2: 2: 6, using coconut oil: clove oil (1:1) as the oil phase and Tween 20: Span 20 (2:1) as the surfactant mixture and 1.0, 2.5, and 5.0% PRE. Cell proliferation, migration, and collagen production of the microemulsion base and microemulsions containing 1.0%, 2.5%, and 5.0% PRE were evaluated. The results revealed that the microemulsion containing 1% PRE had the highest proliferation effect (136.30 ± 3.93% to 152.65 ± 3.48% at concentrations of 10 μg/mL), migration activities (100.00 ± 0.0% at 24 h), and collagen production in human dermal fibroblast (HDF) and human gingival fibroblast (HGF) cells when compared with other formulations or blank. Moreover, the anti-inflammatory activity of microemulsions containing 1% PRE was slightly lower than standard indomethacin. Anti-inflammation of the microemulsion containing PRE exhibited a dose-dependent trend, while 5% PRE was more potent than the standard drug. Considering the potent wound-healing activities and the good anti-inflammatory activity of the microemulsion containing PRE, the microemulsion with 1% PRE was identified as the most suitable oral spray formulation for oral ulcer treatment

High-Throughput Screening of Potential Skin Penetration-Enhancers Using Stratum Corneum Lipid Liposomes: Preliminary Evaluation for Different Concentrations of Ethanol

In this study, we developed a technique for high-throughput screening (HTS) of skin penetration-enhancers using stratum corneum lipid liposomes (SCLLs). A fluorescent marker, sodium fluorescein (FL), entrapped in SCLLs was prepared to provide a preliminary evaluation of the effect of different concentrations of ethanol on the disruption effect of SCLLs, which is an alternative for skin penetration-enhancing effects. In addition, SCLLs containing a fluorescent probe (DPH, TMA-DPH, or ANS) were also prepared and utilized to investigate SCLL fluidity. The results using SCLL-based techniques were compared with conventional skin permeation and skin impedance test using hairless rat skin. The obtained correlations were validated between FL leakage, SCLL fluidity with various probes, or skin impedance and increases in the skin permeation enhancement ratio (ER) of caffeine as a model penetrant. As a result, FL leakage and SCLL fluidity using ANS were considered to be good indices for the skin penetration-enhancing effect, suggesting that the action of ethanol on the SC lipid and penetration-enhancing is mainly on the polar head group of intercellular lipids. In addition, this screening method using SCLL could be utilized as an alternative HTS technique for conventional animal tests. Simultaneously, the method was found to be time-saving and sensitive compared with a direct assay using human and animal skins.A peer-reviewed, Open Access journa

Development of Microemulsions Containing Glochidion wallichianum Leaf Extract and Potential for Transdermal and Topical Skin Delivery of Gallic Acid

Glochidion wallichianum (GW) is a good source of antioxidants, including gallic acid, promoting its development as a microemulsion. We constructed five pseudo-ternary phase diagrams comprising isopropyl myristate (IPM), water, and surfactant mixture (Smix)—i.e., Labrasol®:HCO-40® (1:1) with Transcutol® (1:1, 2:1, 3:1), and Tween80:Span80 (3:2) with Transcutol® or propylene glycol:ethanol (1:1). Additionally, blank and GW extract-loaded microemulsions were prepared at an IPM:Water:Smix ratio of 10:30:60 (high water content) and 30:10:60 (high oil content) from each Smix. The physical characteristics, skin permeation, and disposition were evaluated. The formulations with high water content and conductivities provided higher gallic acid permeation and disposition than those with high oil content. The Smix of Labrasol®:HCO-40® (1:1) and Transcutol® (1:1) promoted the highest gallic acid permeation (enhancement ratio 1.78 ± 0.12) and was suitable for transdermal delivery. However, the 1% hydroxypropyl methylcellulose control gel, the microemulsion with Smix of Labrasol®:HCO-40® (1:1) with Transcutol® (2:1), and Smix of Tween80:Span80 (3:2) with propylene glycol:ethanol (1:1) could provide higher skin accumulation of gallic acid than that with other formulations. The microstructures, ratio of surfactant:cosurfactant, and compositions of microemulsions were found to affect the skin permeation and disposition of gallic acid and require optimization to act as transdermal or topical delivery carriers