TY - JOUR

T1 - Solid state properties and drug release behavior of co-amorphous indomethacin-arginine tablets coated with Kollicoat® Protect

AU - Petry, Ina

AU - Löbmann, Korbinian

AU - Grohganz, Holger

AU - Rades, Thomas

AU - Leopold, Claudia S.

PY - 2017/10

Y1 - 2017/10

N2 - A promising approach to improve the solubility of poorly water-soluble drugs and to overcome the stability issues related to the plain amorphous form of the drugs, is the formulation of drugs as co-amorphous systems. Although polymer coatings have been proven very useful with regard to tablet stability and modifying drug release, there is little known on coating co-amorphous formulations. Hence, the aim of the present study was to investigate whether polymer coating of co-amorphous formulations is possible without inducing recrystallization. Tablets containing either a physical mixture of crystalline indomethacin and arginine or co-amorphous indomethacin-arginine were coated with a water soluble polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat® Protect) and stored at 23 °C/0% RH and 23 °C/75% RH. The solid state properties of the coated tablets were analyzed by XRPD and FTIR and the drug release behavior was tested for up to 4 h in phosphate buffer pH 4.5. The results showed that the co-amorphous formulation did not recrystallize during the coating process or during storage at both storage conditions for up to three months, which confirmed the high physical stability of this co-amorphous system. Furthermore, the applied coating could partially inhibit recrystallization of indomethacin during drug release testing, as coated tablets reached a higher level of supersaturation compared to the respective uncoated formulations and showed a lower decrease of the dissolved indomethacin concentration upon precipitation. Thus, the applied coating enhanced the AUC of the dissolution curve of the co-amorphous tablets by about 30%. In conclusion, coatings might improve the bioavailability of co-amorphous formulations.

AB - A promising approach to improve the solubility of poorly water-soluble drugs and to overcome the stability issues related to the plain amorphous form of the drugs, is the formulation of drugs as co-amorphous systems. Although polymer coatings have been proven very useful with regard to tablet stability and modifying drug release, there is little known on coating co-amorphous formulations. Hence, the aim of the present study was to investigate whether polymer coating of co-amorphous formulations is possible without inducing recrystallization. Tablets containing either a physical mixture of crystalline indomethacin and arginine or co-amorphous indomethacin-arginine were coated with a water soluble polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat® Protect) and stored at 23 °C/0% RH and 23 °C/75% RH. The solid state properties of the coated tablets were analyzed by XRPD and FTIR and the drug release behavior was tested for up to 4 h in phosphate buffer pH 4.5. The results showed that the co-amorphous formulation did not recrystallize during the coating process or during storage at both storage conditions for up to three months, which confirmed the high physical stability of this co-amorphous system. Furthermore, the applied coating could partially inhibit recrystallization of indomethacin during drug release testing, as coated tablets reached a higher level of supersaturation compared to the respective uncoated formulations and showed a lower decrease of the dissolved indomethacin concentration upon precipitation. Thus, the applied coating enhanced the AUC of the dissolution curve of the co-amorphous tablets by about 30%. In conclusion, coatings might improve the bioavailability of co-amorphous formulations.

KW - Co-amorphous

KW - Coating

KW - Drug release

KW - In situ amorphisation

KW - Kollicoat® Protect

KW - Physical stability

U2 - 10.1016/j.ejpb.2017.06.007

DO - 10.1016/j.ejpb.2017.06.007

M3 - Journal article

C2 - 28602869

AN - SCOPUS:85020916102

VL - 119

SP - 150

EP - 160

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -