• Archives of Pharmacal Research
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• 제16권2호
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• pp.123-128
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• 1993

The surface of cyarabine-entrapped albumin microspheres, the surface modified albumin microspheres hsowed remakably incrased hydrophilicity, good dispersability in aqueous medium and reduced aggregation during storage which met the requirements of injectable drug carriers in acqueous vehicle. In vitro cytarabine release from hydrophilic albumin microspheres (HAM) was a function of the cytarabine to albumin ratio, whereas no significant difference in the releasing capacity was obnserved between surface modified HAM within the small size range$(2\;to\;5\mu{m)}$ studied. HAM containing 15-23% drug were gradually degraded by protease and continuously released up to 60% of the total entrapped cytarabine for 6h. These results thus suggest that HAM is a suitable cytarabine carrier which may be injected intraveneously with the benefits of a reduced risk of blood embolism induced by aggregates and prolonged cytarabine release.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.162-168
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• 1992

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 (HAMC 3F), 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 6h, 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 in probably due to the release of "physically associated" 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 monophasic first-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.as HAMC3F.