TY - JOUR
T1 - Amorphization within the tablet
T2 - Using microwave irradiation to form a glass solution in situ
AU - Doreth, Maria
AU - Hussein, Murtadha Abdul
AU - Priemel, Petra A.
AU - Grohganz, Holger
AU - Holm, René
AU - Lopez de Diego, Heidi
AU - Rades, Thomas
AU - Löbmann, Korbinian
PY - 2017/3/15
Y1 - 2017/3/15
N2 - In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study, the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90 kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar to that of a quench cooled, fully amorphous glass solution even though the microwaved samples contained residual crystalline IND.
AB - In situ amorphization is a concept that allows to amorphize a given drug in its final dosage form right before administration. Hence, this approach can potentially be used to circumvent recrystallization issues that other amorphous formulation approaches are facing during storage. In this study, the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90 kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements revealed that with increasing microwaving power and time, the fractions of crystalline IND and amorphous PVP reduced, whereas the amount of in situ formed IND-PVP glass solution increased. Intrinsic dissolution showed that the dissolution rate of the microwaved solid dispersion was similar to that of a quench cooled, fully amorphous glass solution even though the microwaved samples contained residual crystalline IND.
KW - Amorphization
KW - Glass solution
KW - In situ
KW - Microwave radiation
KW - Recrystallization
KW - Tablet
U2 - 10.1016/j.ijpharm.2017.01.035
DO - 10.1016/j.ijpharm.2017.01.035
M3 - Journal article
C2 - 28115260
AN - SCOPUS:85010695842
VL - 519
SP - 343
EP - 351
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
IS - 1-2
ER -