{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:05:59Z","timestamp":1790935559165,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2000,8,1]],"date-time":"2000-08-01T00:00:00Z","timestamp":965088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hydrophilic ionic drugs can be rendered lipophilic by ion-pair formation with hydrophobic counter-ions. This study examines the value of forming ion pairs between anionic salicylate and a series of amines as model cationic counter-ions to facilitate topical delivery and skin penetration. The in-vitro translocation of salicylate ions from a non-aqueous vehicle through human epidermis was estimated in the presence or absence of amines. The distribution into, and accumulation of the salicylate ion in various tissues following topical application to anaesthetised rats were also investigated.<\/jats:p>\n                  <jats:p>Although the epidermal permeation constants of the salicylate-amine ion pairs were lower than that of salicylate itself (enhancement ratios: 0\u201374\u20130.87), salicylate retention and localisation in the underlying rat tissues increased in the presence of some of the counter-ions studied. Salicylate concentrations (\u03bcg (g tissue)\u22121) in the dermis were 877.2 \u00b1 78.6 for salicylate alone and 1098 \u00b1 121.9\u20132586 \u00b1 332.5 for salicylate-amine ion pairs. The levels of salicylate in tissues up to the top muscle layer were 1.2\u20133.7-fold higher in the presence of the counter-ions.<\/jats:p>\n                  <jats:p>It is concluded that, although amine counter-ions have the ability to influence the penetration of salicylate, in-vitro permeability studies do not reflect the in-vivo increases in tissue concentrations resulting from probable changes in systemic clearance.<\/jats:p>","DOI":"10.1211\/0022357001774813","type":"journal-article","created":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T19:43:52Z","timestamp":1058557432000},"page":"929-940","source":"Crossref","is-referenced-by-count":52,"title":["Effect of Ion Pairing with Alkylamines on the In-vitro Dermal Penetration and Local Tissue Disposition of Salicylates"],"prefix":"10.1093","volume":"52","author":[{"given":"Stella A","family":"Megwa","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Queensland , Princess Alexandra Hospital, Woolloongabba, Queensland, 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheree E","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Queensland , Princess Alexandra Hospital, Woolloongabba, Queensland, 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W","family":"Whitehouse","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Queensland , Princess Alexandra Hospital, Woolloongabba, Queensland, 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather A E","family":"Benson","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Queensland , St. Lucia, Queensland, 4067,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Queensland , Princess Alexandra Hospital, Woolloongabba, Queensland, 4102,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,8,1]]},"reference":[{"key":"2024103110051700900_cit1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0376-7388(00)83186-5","article-title":"Coupled transport in membranes II. The mechanism of uranium transport with a tertiary amine","volume":"7","author":"Babcock","year":"1980","journal-title":"J. Membr. Sci."},{"key":"2024103110051700900_cit2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/0223-5234(96)80368-0","article-title":"Chromatographic indicies determined on an immobilized artificial membrane (IAM) column as descriptors of lipophilic and polar interactions of 4-phenyldihydropyridine calcium-channel blockers with biomembranes","volume":"31","author":"Barbato","year":"1996","journal-title":"Eur. J. Med. Chem."},{"key":"2024103110051700900_cit3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-5173(81)90097-1","article-title":"Facilitated percutaneous absorption: a model system","volume":"8","author":"Barker","year":"1981","journal-title":"Int. J. Pharm."},{"key":"2024103110051700900_cit4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/BF00870985","article-title":"Effect of exercise and heat exposure on percutaneous absorption of methyl salicylate","volume":"31","author":"Danon","year":"1986","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"2024103110051700900_cit5","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1021\/ac60279a034","article-title":"Relevance of solubility parameter in ion association extraction systems","volume":"41","author":"Freiser","year":"1969","journal-title":"Anal. Chem."},{"key":"2024103110051700900_cit6","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1023\/A:1011953622052","article-title":"Mechanisms of liposomes\/water partitioning of (p-methylbenzyl)alkylamines","volume":"15","author":"Fruttero","year":"1998","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit7","first-page":"399","article-title":"Ion pairs and solubility behaviour","volume-title":"Solubility Behaviour of Organic Compounds. Vol. XXI of the Techniques of Chemistry Series","author":"Grant","year":"1990"},{"key":"2024103110051700900_cit8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0378-5173(87)90037-8","article-title":"Facilitated transport of cationic drugs across a lipoidal membrane by oleic acid and lauric acid","volume":"37","author":"Green","year":"1987","journal-title":"Int. J. Pharm."},{"key":"2024103110051700900_cit9","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0378-5173(88)90252-9","article-title":"In vitro and in vivo enhancement of skin permeation with oleic and lauric acids","volume":"48","author":"Green","year":"1988","journal-title":"Int. J. Pharm."},{"key":"2024103110051700900_cit10","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1023\/A:1015965801291","article-title":"Enhanced in vitro skin permeation of cationic drugs","volume":"6","author":"Green","year":"1989","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit11","first-page":"233","article-title":"Determination of amines and quaternary ammonium ions as complexes with picrate. Part 3. Relations between extraction constants and the nature of the cation and of the organic phase","volume":"4","author":"Gustavii","year":"1967","journal-title":"Acta Pharm. Suecica"},{"key":"2024103110051700900_cit12","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.2042-7158.1985.tb04951.x","article-title":"Facilitated transport of sodium salicylate across an artificial lipid membrane by azone","volume":"37","author":"Hadgraft","year":"1985","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103110051700900_cit13","first-page":"442","article-title":"Local necrosis and interstitial nephritis due to topical methyl salicylate and menthol","volume":"39","author":"Heng","year":"1987","journal-title":"Cutis"},{"key":"2024103110051700900_cit14","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1023\/A:1011961607089","article-title":"In vitro cutaneous disposition of a topical diclofenac lotion in human skin: effect of a multidose regimen","volume":"15","author":"Hewitt","year":"1998","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit15","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1021\/ac60252a051","article-title":"Ion pair extraction of pharmaceutical amines","volume":"39","author":"Higuchi","year":"1967","journal-title":"Anal. Chem."},{"key":"2024103110051700900_cit16","first-page":"112","article-title":"Extraction of octyl sulfate into 1-pentanol","volume":"17","author":"Johansson","year":"1980","journal-title":"Acta Pharm. Suec."},{"key":"2024103110051700900_cit17","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1248\/bpb.21.599","article-title":"Enhanced in vitro percutaneous penetration of salicylate by ion pair formation with alkylamines","volume":"21","author":"Kadono","year":"1998","journal-title":"Biol. Pharm. Bull."},{"key":"2024103110051700900_cit18","first-page":"97","volume-title":"Design of Topical Drug Products: Pharmaceutics in Drug Design","author":"Katz","year":"1973"},{"key":"2024103110051700900_cit19","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1001\/archderm.1963.01590240026005","article-title":"Preparation of isolated sheets of human stratum corneum","volume":"88","author":"Kligman","year":"1963","journal-title":"Arch. Dermatol."},{"key":"2024103110051700900_cit20","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1159\/000211409","article-title":"In vitro\/in vivo difference in enhanced skin permeation of nicardipine hydrochloride by the 1-methanol-ethanol system","volume":"9","author":"Kobayashi","year":"1996","journal-title":"Skin Pharmacol."},{"key":"2024103110051700900_cit21","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1002\/aic.690240512","article-title":"Selective copper recovery with two types of liquid membrane","volume":"24","author":"Lee","year":"1978","journal-title":"AIChE J."},{"key":"2024103110051700900_cit22","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1248\/bpb.17.1421","article-title":"Relationship between lipophilicity and skin permeability of various drugs from an ethanol\/water\/lauric acid system","volume":"17","author":"Lee","year":"1994","journal-title":"Biol. Pharm. Bull."},{"key":"2024103110051700900_cit23","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/j.2042-7158.1995.tb03266.x","article-title":"Percutaneous absorption of salicylates from some commercially available topical products containing methyl salicylate or salicylate salts in rats","volume":"47","author":"Megwa","year":"1995","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103110051700900_cit24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0378-5173(94)00294-F","article-title":"In vitro evaluation of a series of azone analogs as dermal penetration enhancers: IV","volume":"116","author":"Michniak","year":"1995","journal-title":"Amines. Int. J. Pharm."},{"key":"2024103110051700900_cit25","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1023\/A:1015963128124","article-title":"Ion pair transport across membranes","volume":"6","author":"Neubert","year":"1989","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.2042-7158.1991.tb06667.x","article-title":"Influence of lipophilic counter ions on the transport of ionizable hydrophilic drugs","volume":"43","author":"Neubert","year":"1991","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103110051700900_cit27","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/jps.2600570603","article-title":"Effect of topical vehicle composition on the in vitro release of fluocinolone acetonide and its acetate ester","volume":"57","author":"Poulsen","year":"1968","journal-title":"J. Pharm. Sci."},{"key":"2024103110051700900_cit28","first-page":"35","article-title":"Quaternary ammonium compounds in cosmetics","volume":"91","author":"Quack","year":"1976","journal-title":"Cosmet. Toiletr."},{"key":"2024103110051700900_cit29","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1023\/A:1012076022420","article-title":"Applications of ion-pair concept to hydrophilic substances with special emphasis on peptides","volume":"14","author":"Quintanar-Guerrero","year":"1997","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit30","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/BF00505661","article-title":"Transport of organic ions through lipid bilayers","volume":"316","author":"Ruifrok","year":"1981","journal-title":"Arch. Pharmacol."},{"key":"2024103110051700900_cit31","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1023\/A:1015958526423","article-title":"Optimization of topical therapy: Partitioning of drugs into stratum corneum","volume":"7","author":"Surber","year":"1990","journal-title":"Pharm. Res."},{"key":"2024103110051700900_cit32","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1021\/ed057p509","article-title":"Use of a pH differential to pump an anion across a nonaqueous phase","volume":"57","author":"Thelander","year":"1980","journal-title":"J. Chem. Ed."},{"key":"2024103110051700900_cit33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/jid.1966.4","article-title":"The permeability of mammalian skin to ions","volume":"46","author":"Tregear","year":"1966","journal-title":"J. Invest. Dermatol."},{"key":"2024103110051700900_cit34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0378-5173(82)90122-3","article-title":"Influence of ionisation and ion-pair formation on lipophilicity of some 4-hydroxycoumarin derivatives in the octanol-water system","volume":"12","author":"Van der Giesen","year":"1982","journal-title":"Int. J. Pharm."},{"key":"2024103110051700900_cit35","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1248\/bpb.21.1195","article-title":"Factors determining drug residence in skin during transdermal absorption; studies on \u03b2-blocking agents","volume":"21","author":"Yagi","year":"1998","journal-title":"Biol. Pharm. Bull."},{"key":"2024103110051700900_cit36","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/jps.2600610527","article-title":"Calculation of partial molal volume in micellar systems","volume":"61","author":"Yalkowsky","year":"1972","journal-title":"J. Pharm. Sci."}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1211%2F0022357001774813","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/52\/8\/929\/60263304\/0022357001774813.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/52\/8\/929\/60263304\/0022357001774813.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T06:42:55Z","timestamp":1730356975000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/52\/8\/929\/6157638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8,1]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2000,8,1]]},"published-print":{"date-parts":[[2000,8,1]]}},"URL":"https:\/\/doi.org\/10.1211\/0022357001774813","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2000,8]]},"published":{"date-parts":[[2000,8,1]]}}}