Doreth Maria, Hussein Murtadha Abdul, Priemel Petra A, Grohganz Holger, Holm René, Lopez de Diego Heidi, Rades Thomas, Löbmann Korbinian
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Drug Product Development, Janssen Research and Development, Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
Int J Pharm. 2017 Mar 15;519(1-2):343-351. doi: 10.1016/j.ijpharm.2017.01.035. Epub 2017 Jan 20.
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 90kJ. 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.
原位非晶化是一种在给药前将给定药物在其最终剂型中转化为非晶态的概念。因此，这种方法有可能用于规避其他非晶体制剂方法在储存期间面临的重结晶问题。在本研究中，研究了微波辐射原位制备非晶态固体分散体（玻璃溶液）的可行性。吲哚美辛（IND）和聚乙烯吡咯烷酮K12（PVP）按1:2（w/w）比例压片。为了研究水分含量和能量输入对非晶化程度的影响，将片剂配方储存在不同的相对湿度（32%、43%和54%RH）下，随后使用九种不同的功率-时间组合进行微波处理，最大能量输入为90kJ。X射线粉末衍射（XRPD）结果表明，片剂内高达80%（w/w）的IND可被非晶化。调制差示扫描量热法（mDSC）测量显示，随着微波功率和时间的增加，结晶IND和非晶PVP的比例降低，而原位形成的IND-PVP玻璃溶液的量增加。固有溶出度表明，微波处理的固体分散体的溶出速率与骤冷的完全非晶态玻璃溶液相似，尽管微波处理的样品含有残留的结晶IND。
