Improved bioavailability of para-boronophenylalanine by cyclodextrin complexation.
This study was undertaken to develop an oral dosage form for para-boronophenylalanine (BPA) plus cyclodextrin (CD) for use in the thermal neutron capture therapy for malignant melanoma. Powders of the BPA and CD complexes were obtained in a molar ratio of 1:2. X-ray diffraction of the BPA-CD complexes showed halo patterns that indicated that each complex was in a new solid state as an amorphous compound. The enhancement of BPA solubility by glucosyl (G1)- and maltosyl (G2)-alpha-CD was greater than that with the other CDs. The isolation rate of BPA from its complex was different for each BPA-CD complex. The bioavailability of BPA in rats was improved with oral administration of the BPA-alpha-CD, G1-alpha-CD, and G2-alpha-CD complexes. In contrast, a complex of BPA and dimaltosyl (G2G2) or G2-beta-CD, which had low release rate and low solubility, did not improve the bioavailability of BPA. These results indicate that the solubility and release rate of BPA from a complex in solution are important for the bioavailability of BPA after oral administration of BPA-CD complexes.
Hatanaka
H
H
Hyogo Prefectural Institute of Public Health, Kobe, Japan.
Komada
F
F
Mishima
Y
Y
Okumura
K
K
D000818:Animals; D001682:Biological Availability; D001896:Boron Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000737:chemistry*; D015195:Drug Design; D008297:Male; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D011208:Powders / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D001896:Boron Compounds; D003505:Cyclodextrins; D011208:Powders; D010649:Phenylalanine; C033685:4-boronophenylalanine