Frontiers in Drug Design and Discovery

Volume: 4

Across Skin Barrier: Known Methods, New Performances

Author(s): Krzysztof Cal

Pp: 162-188 (27)

DOI: 10.2174/978160805202810904010162

* (Excluding Mailing and Handling)

Abstract

Skin is still the desirable route for the delivery of drug substances into the human body. Transdermal drug delivery offers many advantages over the conventional oral route of application, such as the elimination of hepatic first-pass effect, reduced side effects, constant concentration of a drug in the blood. Human intact skin is normally permeable for molecules with log P in the range of 1-3, smaller than 500 Da and present in a unionized form. Usually, obtained fluxes of drug substances are too low for the induction of systemic therapeutic effects. It is caused by the specific structure and composition of the outer layer of the skin - the stratum corneum. Closely packed, built as “brick” (corneocytes) and “mortar” (lipid bilayers), the stratum corneum is the most important limiter for transdermal drug delivery. Molecules that permeated the stratum corneum are easily taken up by capillary vessels present in the deeper skin layers. This chapter presents different methods used for skin permeation enhancement. Various drug forms and carriers, chemical permeation enhancers, electrically supported methods and devices, and the stratum corneum bypassing or removing methods are described, and the recent achievements in the field and possible practical use in market products are discussed. The special subchapters are dedicated to the skin disposition of one of the most often used penetration enhancers - terpenes, and the use of cyclodextrins in formulations applied onto the skin.

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      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1518
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1740515802 and j.to_date >= 1740515802 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2208) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1740515802 and j.to_date >= 1740515802 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2208) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59228343 and j.to_ip >=59228343 )) and ((j.from_date <= 1740515802 and j.to_date >= 1740515802 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 2208)
      500μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1549
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 945 and `b`.`banner_from_date` <= 1740515802 and `b`.`banner_to_date` >= 1740515802 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: B
      • 2: 945
      • 3: 1740515802
      • 4: 1740515802
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='a9d95d824c550bfaa66d81c371d8a608'
      190μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        iwnopzcRa99qyahdyWymCflPwaTNg0n0rfuY6d3g
        uc_cart_id
        a9d95d824c550bfaa66d81c371d8a608
        _previous
        array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2208" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/2208
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:17 [ "x-https" => array:1 [ 0 => "1" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] "priority" => array:1 [ 0 => "u=0, i" ] "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6Iis1K3BzUGpsUDNsZE56THdZTGVnWUE9PSIsInZhbHVlIjoiMDlCcE1QY200UDhUVFMxN0piYVltdnhxbHNCd3JDMW54ZnNBb0ZzSlRlUT0iLCJtYWMiOiJlNzBmYWVmOGFjYjJiNDBjODIwZmMxZmYyYTdjNjg1NDViN2ZjYmE5NjViYzllZWI3NzU0YzA1ZjdiOGY4YTA3IiwidGFnIjoiIn0%3Dwayfindertarget=eyJpdiI6Iis1K3BzUGpsUDNsZE56THdZTGVnWUE9PSIsInZhbHVlIjoiMDlCcE1QY200UDhUVFMxN0piYVltdnhxbHNCd3JDMW54ZnNBb0ZzSlRlUT0iLCJtYWMiOiJlNzBmYWVmOGFjYjJi" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate, br, zstd" ] "sec-fetch-dest" => array:1 [ 0 => "document" ] "sec-fetch-user" => array:1 [ 0 => "?1" ] "sec-fetch-mode" => array:1 [ 0 => "navigate" ] "sec-fetch-site" => array:1 [ 0 => "none" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "sec-ch-ua-platform" => array:1 [ 0 => ""Windows"" ] "sec-ch-ua-mobile" => array:1 [ 0 => "?0" ] "sec-ch-ua" => array:1 [ 0 => ""HeadlessChrome";v="129", "Not=A?Brand";v="8", "Chromium";v="129"" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Tue, 25 Feb 2025 20:36:42 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ii82VXN1MzZaRlhCek04Y1BYMkNnemc9PSIsInZhbHVlIjoicHNVcmJ5Y3AyemZZakxLNHBTck0xSHVqZkxqUWdCVnNtQUtxTnltSU03REgwOEl0S3VmaTNJRXgrVkxzRnNNUUZrdEVCT3JYRm1aQ3NTYVJSV3BxTG1JOUNNdU8ycFg5ZGplbjNrcWNzTlhUVTd4VytaSWZVN3JaQTNEVmpYOVEiLCJtYWMiOiI2YjQ2ZjdlNTA0OWFlZGM1NTQ4ZjhhOWNiOTZjMTE5ZmE0ZjMxYTlmZTZmZmJiNWU4ZGI2ODhiMjNmZDIwNDg1IiwidGFnIjoiIn0%3D; expires=Fri, 28 Feb 2025 08:36:42 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6Ii82VXN1MzZaRlhCek04Y1BYMkNnemc9PSIsInZhbHVlIjoicHNVcmJ5Y3AyemZZakxLNHBTck0xSHVqZkxqUWdCVnNtQUtxTnltSU03REgwOEl0S3VmaTNJRXgrVkxzRnNNUUZrdEVCT" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZDM3p3YmtBNS91ZEJVWjZHTGZiWGc9PSIsInZhbHVlIjoiaE1wSGxab0t2SHdKZHRqMW1HenJZb0VBVXArNmhzeW1YdWlZSlZPTGUza25pS3hHQ3hmREVtWkZvanBSZGc1b2x4MHhoWlk0TmU2WmxQQUNsNmFKOGZWOVRuUTJ5NmhvbVhWajhXOTJ0TFB3NW5KK0h2YUxlR2crZ3JxdFA2a1MiLCJtYWMiOiJlZTU1ZGJmOTY0NTM4MDAxMjJhYmYxNWZlNGVkMGNiMTgwODUwNjlhZDI5NGJjOGIzMzVkNjEyMWVjNmMwNDM5IiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InZDM3p3YmtBNS91ZEJVWjZHTGZiWGc9PSIsInZhbHVlIjoiaE1wSGxab0t2SHdKZHRqMW1HenJZb0VBVXArNmhzeW1YdWlZSlZPTGUza25pS3hHQ3hmREVtWkZ" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6Ii82VXN1MzZaRlhCek04Y1BYMkNnemc9PSIsInZhbHVlIjoicHNVcmJ5Y3AyemZZakxLNHBTck0xSHVqZkxqUWdCVnNtQUtxTnltSU03REgwOEl0S3VmaTNJRXgrVkxzRnNNUUZrdEVCT3JYRm1aQ3NTYVJSV3BxTG1JOUNNdU8ycFg5ZGplbjNrcWNzTlhUVTd4VytaSWZVN3JaQTNEVmpYOVEiLCJtYWMiOiI2YjQ2ZjdlNTA0OWFlZGM1NTQ4ZjhhOWNiOTZjMTE5ZmE0ZjMxYTlmZTZmZmJiNWU4ZGI2ODhiMjNmZDIwNDg1IiwidGFnIjoiIn0%3D; expires=Fri, 28-Feb-2025 08:36:42 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6Ii82VXN1MzZaRlhCek04Y1BYMkNnemc9PSIsInZhbHVlIjoicHNVcmJ5Y3AyemZZakxLNHBTck0xSHVqZkxqUWdCVnNtQUtxTnltSU03REgwOEl0S3VmaTNJRXgrVkxzRnNNUUZrdEVCT" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZDM3p3YmtBNS91ZEJVWjZHTGZiWGc9PSIsInZhbHVlIjoiaE1wSGxab0t2SHdKZHRqMW1HenJZb0VBVXArNmhzeW1YdWlZSlZPTGUza25pS3hHQ3hmREVtWkZvanBSZGc1b2x4MHhoWlk0TmU2WmxQQUNsNmFKOGZWOVRuUTJ5NmhvbVhWajhXOTJ0TFB3NW5KK0h2YUxlR2crZ3JxdFA2a1MiLCJtYWMiOiJlZTU1ZGJmOTY0NTM4MDAxMjJhYmYxNWZlNGVkMGNiMTgwODUwNjlhZDI5NGJjOGIzMzVkNjEyMWVjNmMwNDM5IiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InZDM3p3YmtBNS91ZEJVWjZHTGZiWGc9PSIsInZhbHVlIjoiaE1wSGxab0t2SHdKZHRqMW1HenJZb0VBVXArNmhzeW1YdWlZSlZPTGUza25pS3hHQ3hmREVtWkZ" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "iwnopzcRa99qyahdyWymCflPwaTNg0n0rfuY6d3g" "uc_cart_id" => "a9d95d824c550bfaa66d81c371d8a608" "_previous" => array:1 [ "url" => "https://alpha.eurekaselect.com/chapter/2208" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-25 20:36:42GET/chapter/2208112192