Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-_L-Methionine

( Ki Taek Kim ),( Ji Su Kim ),( Min-hwan Kim ),( Ju-hwan Park ),( Jae-young Lee ),( Wooin Lee ),( Kyung Kuk Min ),( Min Gyu Song ),( Choon-young Choi ),( Won-serk Kim ),( Hee Kyung Oh ),( Dae-duk Kim 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.4

S-methyl-_L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Formulation of Liposome for Topical Delivery of Arbutin

Wen, Ai-Hua,Choi, Min-Koo,Kim, Dae-Duk The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.12

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of $179.9{\sim}212.8\;nm$ in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

Formulation of Liposome for Topical Delivery of Arbutin

Ai-Hua Wen,최민구,김대덕 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.12

The aims of this study were to encapsulate arbutin (AR) in liposome to enhance the skin-whitening activity, and to investigate the effect of liposome formulation on the entrapment efficiency (EE%), skin permeation rate and skin deposition. The liposomes were prepared by a film dispersion method with several different formulations and were separated from the solution by using the gel-filtration method. The physical (size distribution, morphology) and chemical (drug entrapment efficiency, hairless mouse skin permeation and deposition) properties of liposomes were characterized. The entrapment efficiency in all liposome formulations varied between 4.35% and 17.63%, and was dependent on the lipid content. The particle sizes of liposomes were in the range of 179.9~212.8 nm in all liposome formulations. Although the permeation rate of AR in the liposome formulations decreased compared with AR solution, the deposition amount of AR in the epidermis/dermis layers increased in AR liposomal formulation. These results suggest that liposomal formulation could enhance the skin deposition of hydrophilic skin-whitening agents, thereby enhancing their activities.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-L-Methionine

김기택,김지수,김민환,박주환,이재영,이우인,민경국,송민규,최춘영,김원석,오희경,김대덕 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.4

S-methyl-L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-ʟ-Methionine

Kim, Ki Taek,Kim, Ji Su,Kim, Min-Hwan,Park, Ju-Hwan,Lee, Jae-Young,Lee, WooIn,Min, Kyung Kuk,Song, Min Gyu,Choi, Choon-Young,Kim, Won-Serk,Oh, Hee Kyung,Kim, Dae-Duk The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.4

S-methyl-$\small{L}$-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

Formulation and evaluation of microsponge gel for topical delivery of fluconazole for fungal therapy

Nirav Patel,Niyati Padia,Neha Vadgama,Mihir Raval,Navin Sheth 한국약제학회 2016 Journal of Pharmaceutical Investigation Vol.46 No.3

The aim of the present research was to develop Fluconazole loaded microsponge-based topical delivery system for controlled release and enhanced drug deposition in the skin. Microsponges containing fluconazole were prepared by an emulsion solvent diffusion method. The effect of formulation variables (drug: polymer ratio, internal phase volume and amount of emulsifier) and process variables (stirring time and stirring speed) on the physical characteristics of microsponges like Production yield, Mean particle size, Entrapment efficiency were investigated. The effect of internal phase volume and amount of emulsifier on the physical characteristics of microsponges were examined on optimized drug/polymer ratio, stirring speed and stirring time by 32 factorial design. The optimized microsponges were dispersed into a hydrogel and evaluated. In vitro drug release, Ex vivo drug deposition, primary skin irritancy study and In vivo antibacterial activity of fluconazole-loaded formulations were studied. Spherical and porous FLU microsponge particles were obtained. From 32 factorial design, it was concluded that optimized microsponge possess particle size, production yield and entrapment efficiency of 2.45 lm, 77.38 and 92.33 %, respectively. Microspongeloaded gels demonstrated controlled release, no irritancy to rat skin and antifungal activity. An In vivo skin deposition study demonstrated four fold higher retention in the stratum corneum layer as compared with marketed cream. Microsponges-based gel formulations showed prolonged efficacy in mouse surgical wound model infected with Candida spp. Fluconazole was stable in topical formulations and showed enhanced retention in the skin indicating better potential of the delivery system for treatment of primary and secondary skin infections.

Formulation and evaluation of spray dried liposomes of lopinavir for topical application

Mithun G. Maniyar,Chandrakant R. Kokare 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.2

The anti-HIV therapy is the most capable disease management approach for HIV-AIDS, but its purpose could not fulfill to get maximum bioavailability. In this study, an attempt has been made to develop lopinavir–loaded phospholipid vesicles by using the spray-drying method. Lopinavir loaded spray-dried powder (L-SDP) has been transformed into the vesicles and characterized for physico-chemical properties. Penetration enhancers (PEs) containing cream have been formulated to deliver L-SDP through the skin. Vesicle showed globular shape, 270 nm particle size, polydispersity index (PDI) 0.239, − 34.34 mV zeta potential with 56.38 ± 1.24% entrapment efficiency. In-vitro drug release (%) study through a cellophane membrane showed extended drug release of drug from liposomal formulations in contrast to hydro-alcoholic drug solution (HAS), which released most of the drug within 3–4 h and higher drug release than drug cream. The penetration enhancers (PEs) were selected after investigating their ability to enhance membrane fluidity by FTIR, which showed encouraging outcomes. L-SDP cream with PEs subjected for ex-vivo drug release and skin deposition study using goat facial skins. The cream showed superior drug deposition as well as drug release. The cream containing peppermint oil showed tenfold higher (57.2%) than drug cream (5.91%) and olive oil showed 44.9% drug release.

Enhanced In Vitro Skin Deposition Properties of Retinyl Palmitate through Its Stabilization by Pectin

( Dong Churl Suh ),( Yeong Seok Kim ),( Hyeong Min Kim ),( Ji Eun Ro ),( Seong Wan Cho ),( Gyiae Yun ),( Sung Up Choi ),( Jae Hwi Lee ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.1

The purpose of this study was to examine the effect of stabilization of retinyl palmitate (RP) on its skin permeation and distribution profiles. Skin permeation and distribution study were performed using Franz diffusion cells along with rat dorsal skin, and the effect of drug concentration and the addition of pectin on skin deposition profiles of RP was observed. The skin distribution of RP increased in a concentration dependent manner and the formulations containing 0.5 and 1 mg of pectin demonstrated significantly increased RP distributions in the epidermis. Furthermore, it was found that skin distribution of RP could be further improved by combined use of pectin and ascorbyl palmitate (AP), due largely to their anti-oxidative effect. These results clearly demonstrate that the skin deposition properties of RP can be improved by stabilizing RP with pectin. Therefore, it is strongly suggested that pectin could be used in the pharmaceutical and cosmetic formulations as an efficient stabilizing agent and as skin penetration modulator.

Ultra deformable vesicles for boosting transdermal delivery of 2-arylpropionic acid class drug for management of musculoskeletal pain

Kaul Shreya,Jain Neha,Nagaich Upendra 한국약제학회 2022 Journal of Pharmaceutical Investigation Vol.52 No.2

Purpose The aim of this investigation was to formulate and evaluate naproxen transethosomal gel for sustained transdermal delivery for the management of musculoskeletal pain. Methods In this examination naproxen sodium-loaded transethosomes were developed by ethanol injection method. A 9 run, 2-factor, 3-level factorial design was used to optimize naproxen-transethosomes. Transethosomal formulations were then incorporated into hydrogel made of gelling agent carbopol 940. The formulated transethosomes were characterized for particle size, entrapment efficiency, zeta potential, in-vitro release, ex-vivo drug permeation study, drug deposition study, and in-vivo anti-inflammatory study. Results The results exhibited that the particle size were in the range of 56.94 ± 0.12 nm to 291.7 ± 0.09 nm. The transethosomes had higher entrapment efficiency in between 66.23 ± 1.52 and 93.11 ± 0.96% and exhibited a spherical morphology when examined by TEM analysis. The in-vitro skin permeation study carried out on rat skin exhibited enhanced skin deposition with lesser systemic absorption. The in-vivo studies carried out on rats showed the superiority of naproxen transethosomal gel in reducing the edema rate. Conclusion The results obtained all together demonstrated that the formulated transethosomal gel possessed a smaller particle size, high entrapment efficiency along higher skin deposition rate which is required in getting relief from musculoskeletal pain. The developed formulation could be regarded as an ideal substitute for the conventional gel for the management of musculoskeletal pain.

Topical delivery of Idebenone using nanostructured lipid carriers: evaluations of sun-protection and anti-oxidant effects

Sachin S. Salunkhe,Neela M. Bhatia,Varsha B. Pokharkar,Jyoti D. Thorat,Manish S. Bhatia 한국약제학회 2013 Journal of Pharmaceutical Investigation Vol.43 No.4

The objective of present study was to develop nanostructured lipid carriers (NLC) for topical delivery of antioxidant drug and evaluation of its sun protection efficacy. In the present study attempts have been made to formulate Idebenone loaded nanostructured lipid carriers (INLC) by using solvent precipitation method. Preformulation study evidenced for selection of Captex 500 P as an oil phase in which Idebenone has saturation solubility of 0.266 ±0.032 g/ml. Compritol 888 ATO and ethanol were selected as solid lipid and solvent respectively. Surfactant and cosurfactant as Labrasol and Transcutol P have given stable formulations on the basis of HLB required for stabilization,respect to oil phase. INLC has particle size of 605 ±4.01 nm and %EE of 82.58 ± 2.20 %. Optimized batches were subjected for crystallographic investigation, in vitro skin permeation study, drug deposition study, SPF determination and antioxidant activity. XRD, DSC studies illustrated that partial amorphization of Idebenone by molecularly dispersion within lipid blend leads for entrapment of drug. Permeation data showed that optimized INLC has flux value (Jss)of 7.87 lg cm-2 h-1. High significance (P\0.001) of drug deposition in skin was observed between INLC and plain Idebenone gel. SPF value for INLC has 23which represents that lipid nanocarriers have standards of blocking of 94–96 % of UVB rays. Such high skin deposition and SPF leads to more antioxidant effect of formulations. Hence lipid nanocarriers such as NLC have potential as an antioxidant and sun protection for topical drug delivery.