Design of long-acting formulation of protein drugs with a double-layer structure and its application to rhG-CSF.
In order to design a sustained-release formulation of protein drugs characterized by excellent long-acting properties without an initial burst, a new double-layer minipellet (DL-MP) in which the lateral side of a matrix-type sustained-release formulation 'minipellet' using collagen as a carrier was coated with collagen was designed, and its performance was evaluated. In a DL-MP using bovine serum albumin (BSA) as a model drug, the initial burst observed with a single-layer minipellet (SL-MP) was effectively inhibited in an in vitro release test, and the addition of additives such as chondroitin sulfate (CS) permitted control of release rate. This formulation of recombinant human granulocyte colony-stimulating factor (rhG-CSF) was then prepared, and its characteristics were determined in normal rats. It was found that blood rhG-CSF concentration was maintained for about 1 week after administration of a DL-MP with additional CS, with persistent increase in white cell count. The results of this study indicated that DL-MP was useful as a long-acting formulation of rhG-CSF characterized by excellent long acting properties without an initial burst.
Maeda
Hiroo
H
Formulation Research Laboratories, Sumitomo Pharmaceuticals Co. Ltd., 3-45 Kurakakiuchi 1-Chome, Ibaraki-shi, Osaka 567-0878, Japan. maedah@sumitomopharm.co.jp
Nakagawa
Takashi
T
Adachi
Noriyuki
N
Sakai
Yasuyuki
Y
Yamamoto
Tomonaga
T
Matsuoka
Akio
A
Sano
Akihiko
A
Satoh
Yukihiro
Y
Miyata
Teruo
T
Fujioka
Keiji
K
D000818:Animals; D002417:Cattle; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004343:Drug Implants; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D006801:Humans; D011506:Proteins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D011994:Recombinant Proteins; D013678:Technology, Pharmaceutical / Q000379:methods*
D003692:Delayed-Action Preparations; D004343:Drug Implants; D011506:Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor