TY - JOUR

T1 - Polymorphism of chlorpropamide on liquid-assisted mechanical treatment

T2 - Choice of liquid and type of mechanical treatment matter

AU - Bouvart, Nadia

AU - Palix, Roland Marie

AU - Arkhipov, Sergey G.

AU - Tumanov, Ivan A.

AU - Michalchuk, Adam A.L.

AU - Boldyreva, Elena V.

PY - 2018/4/7

Y1 - 2018/4/7

N2 - Different types of mechanical treatment (tableting, grinding, milling, etc.) are important technological operations in the pharmaceutical industry. Solid materials are not merely comminuted during such treatment, but can undergo polymorphic transitions and amorphisation. A liquid is often added to the solid sample on purpose, e.g. in order to facilitate comminution. In many cases, liquid is present inadvertently, either as a result of trace solvent following up-stream operations, or sorbed from the atmosphere. This work explores the liquid-assisted mechanical treatment of two metastable forms of a model pharmaceutical compound chlorpropamide (CPA), namely the β- and ϵ-forms. We investigate the stability of these polymorphs to mechanical treatment in the presence of a series of fluids that have affinity for different fragments of the CPA molecule. In addition to variation in fluids, the effect of different mechanical treatment is explored, employing model shear and restricted impact devices, alongside grinding in a mortar. CPA offers a clear example of the drastically different results of shear and impact on mechanochemical polymorphism, on the importance of the careful selection of solvent for liquid-assisted treatment, and on the possible role of even trace quantities of solvent. Further, this work demonstrates the importance of the starting polymorph in determining the outcome of a mechanochemical process. All of these factors can have notable consequence on the outcome of technological operations that include mechanical treatment.

AB - Different types of mechanical treatment (tableting, grinding, milling, etc.) are important technological operations in the pharmaceutical industry. Solid materials are not merely comminuted during such treatment, but can undergo polymorphic transitions and amorphisation. A liquid is often added to the solid sample on purpose, e.g. in order to facilitate comminution. In many cases, liquid is present inadvertently, either as a result of trace solvent following up-stream operations, or sorbed from the atmosphere. This work explores the liquid-assisted mechanical treatment of two metastable forms of a model pharmaceutical compound chlorpropamide (CPA), namely the β- and ϵ-forms. We investigate the stability of these polymorphs to mechanical treatment in the presence of a series of fluids that have affinity for different fragments of the CPA molecule. In addition to variation in fluids, the effect of different mechanical treatment is explored, employing model shear and restricted impact devices, alongside grinding in a mortar. CPA offers a clear example of the drastically different results of shear and impact on mechanochemical polymorphism, on the importance of the careful selection of solvent for liquid-assisted treatment, and on the possible role of even trace quantities of solvent. Further, this work demonstrates the importance of the starting polymorph in determining the outcome of a mechanochemical process. All of these factors can have notable consequence on the outcome of technological operations that include mechanical treatment.

KW - WATER-SOLUBLE DRUGS

KW - HIGH-PRESSURE POLYMORPHISM

KW - PHARMACEUTICAL COCRYSTALS

KW - CONFORMATIONAL POLYMORPHISM

KW - MECHANOCHEMICAL SYNTHESIS

KW - SOLID-STATE

KW - FORM

KW - CRYSTALS

KW - NANOSUSPENSIONS

KW - FORMULATION

UR - http://www.scopus.com/inward/record.url?scp=85044525259&partnerID=8YFLogxK

U2 - 10.1039/c7ce02221b

DO - 10.1039/c7ce02221b

M3 - Article

AN - SCOPUS:85044525259

VL - 20

SP - 1797

EP - 1803

JO - CrystEngComm

JF - CrystEngComm

SN - 1466-8033

IS - 13

ER -