title: A new injectable liquid crystal system for one month delivery of leuprolide.
abstract: An injectable liquid crystal-forming system (LCFS) was prepared by using sorbitan monooleate (SMO) as a new liquid crystal-forming material for injections, and its potential use of clinically available sustained-release formulation was evaluated. LCFS was prepared using SMO mixed with phosphatidyl choline and tocopherol acetate, and contained 3.75 mg of leuprolide acetate as a monthly dose in 90 μl in liquid form. The semi-solid mesophase was formed from the liquid LCFS when it contacted water. The mesophase showed typical characteristics of the liquid crystalline phase, which was classified as the hexagonal phase. The safety of the LCFS was studied by an in vitro extraction colony assay and by examining the injection site in rats and white rabbits after an autopsy. Both in vitro release test and in vivo pharmacokinetic and pharmacodynamic studies showed a sustained release of leuprolide. When compared with a commercial depot formulation of leuprolide, the LCFS showed a similar AUClast value and significantly reduced initial burst with sufficient suppression of testosterone after subcutaneous injections in rats and dogs. The LCFS can serve as a new type of sustained-release injection formulation for its safety, ease of preparation, and sustained release properties.
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Min-Hyo
authors.initials: MH
authors.lastname: Ki
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea; School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Jong-Lae
authors.initials: JL
authors.lastname: Lim
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Ko
authors.affiliation: Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., 464-3 Jung-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-916, Republic of Korea.
authors.forename: So-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Ji-Eon
authors.initials: JE
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ddkim@snu.ac.kr.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004285:Dogs; D005260:Female; D006601:Hexoses / Q000737:chemistry*; D006801:Humans; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D050866:Liquid Crystals / Q000737:chemistry*; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D006601:Hexoses; C018665:sorbitan monooleate; D016729:Leuprolide
keywords: Hexagonal phase; Leuprolide; Liquid crystal; Pharmacokinetics; Sustained release injection