TY - JOUR
T1 - Refining stability and dissolution rate of amorphous drug formulations
AU - Grohganz, Holger
AU - Priemel, Petra A
AU - Löbmann, Korbinian
AU - Nielsen, Line Hagner
AU - Laitinen, Riikka
AU - Mullertz, Anette
AU - Van den Mooter, Guy
AU - Rades, Thomas
PY - 2014/6
Y1 - 2014/6
N2 - Introduction: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its amorphous counterpart is often seen as a potential solution to increase the solubility. However, amorphous systems are physically unstable. Therefore, pharmaceutical formulations scientists need to find ways to stabilise amorphous forms. Areas covered: The use of polymer-based solid dispersions is the most established technique for the stabilisation of amorphous forms, and this review will initially focus on new developments in this field. Additionally, newly discovered formulation approaches will be investigated, including approaches based on the physical restriction of crystallisation and crystal growth and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. Expert opinion: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed.
AB - Introduction: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its amorphous counterpart is often seen as a potential solution to increase the solubility. However, amorphous systems are physically unstable. Therefore, pharmaceutical formulations scientists need to find ways to stabilise amorphous forms. Areas covered: The use of polymer-based solid dispersions is the most established technique for the stabilisation of amorphous forms, and this review will initially focus on new developments in this field. Additionally, newly discovered formulation approaches will be investigated, including approaches based on the physical restriction of crystallisation and crystal growth and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. Expert opinion: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed.
U2 - 10.1517/17425247.2014.911728
DO - 10.1517/17425247.2014.911728
M3 - Journal article
C2 - 24754747
SN - 1742-5247
VL - 11
SP - 977
EP - 989
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
IS - 6
ER -