著者

藤堂 浩明 齋藤 美幸 鈴木 宏宙 井上 裕 高山 幸三 杉林 堅次

出版者

公益社団法人 日本薬剤学会

雑誌

薬剤学 (ISSN:03727629)

巻号頁・発行日

vol.81, no.1, pp.111-120, 2021 (Released:2021-01-01)

参考文献数

6

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It is important when developing effective and safe pharmaceutical products to select adequate active components and formulations as well as to design their containers and devices. Minoxidil was developed as a direct over-the-counter (OTC) drug in 1999 and has long been marketed only by one original company. Recently, many generic products have been marketed. However, the shape and type of the containers for these generic products differ from that of the original product, leading to a possibility that the amount of minoxidil applied by patients may differ. In the present study, the original and three typical generic products with 5% minoxidil external formulations were evaluated for their filling amounts, single application amounts, extent of distribution on application, ability to reach the scalp, and dripping properties. As a result, statistically significant differences were found in the filling amounts and ability to reach to the scalp between the products due to differences in the nozzle shape of the container. In addition, a large variation was observed in some of the generic products in terms of the drug liberation. These results indicate that it is important to suitably design and adequately evaluate the container for OTC products such as minoxidil formulations, which can exhibit toxicity from overuse, and that are easily purchased by consumers.

著者

木村 恵理子 藤堂 浩明 杉林 堅次

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.3, pp.319-324, 2012-03-01 (Released:2012-03-01)

参考文献数

19

被引用文献数

2 2

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Human beings are exposed or otherwise a subjected to a various chemical compounds. Various nanomaterials are contained in the chemical compounds which are used in many fields. Nanomaterials are also used in cosmetics: titanium dioxide and zinc oxide are examples. Consumers who apply cosmetics to their skin as well as workers at industrial plants may thus be exposed to these nanoparticles. Therefore, it is of great importance to evaluate the safety of these nanoparticles. In this review, we describe the possibility of nanoparticle penetration to skin following exposure, which makes it urgent to evaluate the safety factors. In general, it is necessary to take account of the desquamation rate of the stratum corneum and the permeation pathway and size of nanoparticles when considering such penetration. One layer of the human stratum corneum is peeled off per day. Therefore, a chemical compound of which the skin penetration is lower than the desquamation rate does not permeate through the skin, when the compound infiltrates the stratum corneum. Hence, compounds with a molecular weight of more than 500 Daltons do not permeate through the stratum corneum. However, we must also pay attention to the appendage routes, although the aforementioned layer is the primary permeation route of nanoparticles. The contribution of appendage routes must be taken into consideration.

著者

藤堂 浩明

出版者

日本香粧品学会

雑誌

日本香粧品学会誌 (ISSN:18802532)

巻号頁・発行日

vol.45, no.2, pp.106-111, 2021-06-30 (Released:2022-06-30)

参考文献数

9

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The skin concentration of topically applied cosmetic active ingredients is very important for evaluating cosmetics. However, the direct measurement of drug concentration in the membrane has several problems. Generally, controlling the removal of the drug formulation from the membrane surface is very difficult. Hard cleaning of the membrane surface decreases the membrane concentration, whereas inadequate cleaning may leave the drug formulation on the membrane. In the present paper, relationship between skin permeation and skin concentration is shown and research results with verification result for utilization to dose setting method guideline for human long-duration trials (Safety) is also introduced. I hope this paper will be helpful to ensure the efficacy and safety of cosmetic products.

著者

杉野 雅浩 藤堂 浩明 杉林 堅次

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.12, pp.1453-1458, 2009-12-01 (Released:2009-12-01)

参考文献数

14

被引用文献数

12 14

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Transdermal Drug Delivery Systems (TDDS), where active drugs must be absorbed into the systemic circulation after penetrating the skin barrier, were first launched in 1979, and about 10 TDDS containing different kinds of drugs were developed during the initial decade. Interestingly, a developmental rush has come again in the present century. Various penetration-enhancing approaches to improve drug permeation of the skin (stratum corneum) have been attempted. These approaches are of two types: chemical and physical. Examples of the chemical approach are enhancers such as alcohol, monoterpenes and fatty acid esters, as well as chemical modification of prodrugs. In contrast, physical approaches include the use of electrical-, thermal- and mechanical-energy, as well as microneedles, needle-free injectors or electroporation to completely or partially evade the barrier function in the stratum corneum. The chemical approaches are mainly effective in increasing the skin permeation of low-molecular chemicals, whereas physical means are effective for these chemicals but also high-molecules like peptides, proteins and nucleotides (DNA or RNA). Marked development has been observed in these physical means in the past decade. In addition, recent developments in tissue engineering technologies enables the use of cultured skin containing keratinocytes and fibroblasts as a TDDS. An effective “cell delivery system” may be a reality in the near future. This paper will look back on the 30-year history of TDDS and evaluate the feasibility of a new generation of these systems.

著者

用量設定法ガイドライン検討委員会 藤堂 浩明 足立 浩章 今井 教安 上中 麻規子 内田 崇志 大谷 道輝 澤田 美月 成田 昌稔 西島 貴史 野村 宜史 宮坂 美行 畑尾 正人 増永 卓司 山口 雅彦 佐々 齊 知久 真巳 川田 裕三 古屋 律子 藤井 まき子

出版者

日本香粧品学会

雑誌

日本香粧品学会誌 (ISSN:18802532)

巻号頁・発行日

vol.43, no.2, pp.99-108, 2019-06-30 (Released:2020-06-30)

参考文献数

15

被引用文献数

1

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The skin concentration of topically applied cosmetic active ingredients is very important for evaluating cosmetics. However, a large variation is often observed in finite dose experiments due to the evaporation of volatile components in the formulation and difficulties for applying formulation uniformly. In addition, steady-state skin concentration could not be attained even after several hours of application. In this verification report, we conducted in vitro skin permeation experiment with an infinite dose to confirm whether formulation with the highest skin permeation would also show the highest skin concentration. Three formulations, lotion, milk, and cream, and the mixture of these formulations containing isopropyl methyl phenol (IPMP) as a model ingredient were applied to excised human skin in eight research facilities. The present experiment was conducted with receptor solution containing 1.0% of Brij 98 in order to increase solubility of IPMP in the receptor fluid without changing skin integrity. The obtained results were consistent among the facilities in the following order of skin permeation (lotion>milk>cream≅the mixture) and corresponded with that of the skin concentration. This result showed that evaluation of topical formulations with in vitro skin permeation experiment with an infinite dose could identify the formulation which exhibited the highest steady-state skin concentration of cosmetic active ingredients. In addition, experiment with mixture formulation might reveal changes in skin permeability associated with changes in thermodynamic activity of IPMP after co-application of several formulations on the skin.

著者

藤堂 浩明 齋藤 美幸 鈴木 宏宙 井上 裕 高山 幸三 杉林 堅次

出版者

日本薬剤学会

雑誌

Journal of Pharmaceutical Science and Technology, Japan (ISSN:03727629)

巻号頁・発行日

vol.81, no.1, pp.111-120, 2021-01

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It is important when developing effective and safe pharmaceutical products to select adequate active components and formulations as well as to design their containers and devices. Minoxidil was developed as a direct over-the-counter (OTC) drug in 1999 and has long been marketed only by one original company. Recently, many generic products have been marketed. However, the shape and type of the containers for these generic products differ from that of the original product, leading to a possibility that the amount of minoxidil applied by patients may differ. In the present study, the original and three typical generic products with 5% minoxidil external formulations were evaluated for their filling amounts, single application amounts, extent of distribution on application, ability to reach the scalp, and dripping properties. As a result, statistically significant differences were found in the filling amounts and ability to reach to the scalp between the products due to differences in the nozzle shape of the container. In addition, a large variation was observed in some of the generic products in terms of the drug liberation. These results indicate that it is important to suitably design and adequately evaluate the container for OTC products such as minoxidil formulations, which can exhibit toxicity from overuse, and that are easily purchased by consumers.

著者

藤堂 浩明 杉林 堅次

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.20, no.4, pp.452-459, 2005-07-10 (Released:2008-12-09)

参考文献数

31

被引用文献数

2 2

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薬物の皮膚適用は, 肝初回通過効果を回避でき, 長期連続投与が可能であるなどの理由から, 全身治療を目的とした薬物投与法として注目されている. しかしながら, 多くの薬物において皮膚透過性はきわめて低いという問題点があり, 実用化には吸収促進法の利用が不可欠である. 現在までに確立されている吸収促進法は, 大きく物理学的促進法と化学的方法の二つがあげられる. これらの技術の進歩により, 従来型低分子有機化合物のみならず, ペプチド, 蛋白質, 核酸医薬品などの高分子量物質に対しても経皮薬物送達システムの適用が可能になりつつある.