caa a22 4500 469050241 CHVBK 20180323132828.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF02974093 doi (NATIONALLICENCE)springer-10.1007/BF02974093 Preparation and In vitro release characteristics of hydrophilic albumin microspheres containing methotrexate and methotrexate-human serum albumin conjugates [Elektronische Daten] [Sung-Joo Hwang, Myung Lee, Chong-Kook Kim] Release characteristics of five different types of hydrophilic albumin microspheres (HAM) containing different ratios of methotrexate-albumin (MTX-HSA) conjugates to free MTX; 1∶0 (HAMC), 3∶1 (HAMC3F), 1∶1 (HAMCF), 1∶3 (HAMCF3) and 0∶1 (HAMF) were investigated in the absence or presence of protease using dissolution tester. In all the HAMs studied except HAMC, the MTX was released bi-exponentially in the absence of protease; an initial fast release period up to approximately 6 h, and thereafter the release rate was very much slower. The fast release of MTX from the HAMs (such as HAMC3F, HAMCF, HAMCF3 and HAMF) at the initial phase is probably due to the release of "physically associated” MTX on the surface and/or entrapped in the near inner surface of HAMs and the slow release at the second phase is due to the release of entrapped free MTX from the core of the HAMs. The initial rate constants were 7.2, 8.7, 8.5 and 5.9 times greater than the second rate constants for HAMF, HAMCF3, HAMCF and HAMC3F, respectively. MTX release from HAMC was very slow and mono-phasic. It was at most 2.2% of the total entrapped amount by 24 h. The protease accelerated the release of MTX from the HAMs. The percentages of MTX released from HAMs up to 24 h were 100, 89.0, 75.0, 66.0 and 61.0% for HAMF, HAMCF3, HAMCF, HAMC3F and HAMC, respectively in the presence of protease and the corresponding values in the absence of protease were 30.2, 19.0, 10.0, 6.5 and 2.2%, respectively.In vitro release of MTX in the presence of protease varied according to the ratios of MTX-HSA conjugates to MTX; the data set from HAMF, HAMCF3 and HAMCF fits better to monophasic first-order profile more adequately than to zero-order profile, that of HAMC3 F to mono-phasic zero-order, and that of HAMC to bi-phasic zero-order. Above results suggested that zero-order release rate can be achieved by adjusting the ratio of MTX-HSA conjugates to MTX in the preparation of HAMs such as HAMC3F. The Pharmaceutical Society of Korea, 1992 Hydrophilic albumin microspheres nationallicence methotrexate nationallicence methotrexate-human serum albumin conjugates nationallicence in vitro drug release nationallicence drug release by protease nationallicence zero-order release nationallicence Hwang Sung-Joo College of Pharmacy, Chungnam National University, 305-764, Taejeon, Korea aut Lee Myung College of Pharmacy, Seoul National University, 151-742, Seoul, Korea aut Kim Chong-Kook College of Pharmacy, Seoul National University, 151-742, Seoul, Korea aut Archives of Pharmacal Research Pharmaceutical Society of Korea 15/2(1992-06-01), 162-168 0253-6269 15:2<162 1992 15 12272 https://doi.org/10.1007/BF02974093 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02974093 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hwang Sung-Joo College of Pharmacy, Chungnam National University, 305-764, Taejeon, Korea aut NATIONALLICENCE 700 1- Lee Myung College of Pharmacy, Seoul National University, 151-742, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Chong-Kook College of Pharmacy, Seoul National University, 151-742, Seoul, Korea aut NATIONALLICENCE 773 0- Archives of Pharmacal Research Pharmaceutical Society of Korea 15/2(1992-06-01), 162-168 0253-6269 15:2<162 1992 15 12272 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer