title: Novel methods for the assessment of miscibility of amorphous drug-polymer dispersions.
abstract: A typical approach to miscibility analysis of amorphous drug-excipient dispersions involves measuring the glass transition temperature, T(g), using differential scanning calorimetery (DSC). Recently, we discussed two computational methods for the miscibility analysis of amorphous dispersions using X-ray powder diffraction (XRPD). Those methods could be used to qualify an amorphous dispersion as miscible or phase separated, with the implication that miscible dispersions are more stable towards recrystallization. The methods were limited by the need for reference XRPD patterns of both the amorphous drug and excipient. In this work, we propose two additional computational approaches that overcome that limitation and can be used to quantify the degree of miscibility in an amorphous dispersion. The first approach is based on the use of a Pure Curve Resolution Method to extract unknown amorphous references as well as qualify miscibility. The second method, based on Alternate Least Squares, can then be used to quantify the degree of miscibility by determining the nearest neighbor (NN) coordination number for the active pharmaceutical ingredient (API) and excipient. It is proposed that the NN coordination number is related to physical stability.
authors.affiliation: iigor@cs.wisc.edu
authors.forename: Igor
authors.initials: I
authors.lastname: Ivanisevic
authors.forename: Simon
authors.initials: S
authors.lastname: Bates
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
mesh_terms: D000465:Algorithms; D005079:Excipients / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D033362:Powder Diffraction / Q000379:methods*; D012995:Solubility; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers