title: Mechanistic and Kinetic Insight into Spontaneous Cocrystallization of Isoniazid and Benzoic Acid.
abstract: Solid-state cocrystallization is of contemporary interest because it offers an easy and efficient way to produce cocrystals, which are recognized as prospective pharmaceutical materials. Research explaining solid-state cocrystallization mechanisms is important but still too scarce to give a broad understanding of factors governing and limiting these reactions. Here we report an investigation of the mechanism and kinetics of isoniazid cocrystallization with benzoic acid. This reaction is spontaneous; however, its rate is greatly influenced by environmental conditions (humidity and temperature) and pretreatment (milling) of the sample. The acceleration of cocrystallization in the presence of moisture is demonstrated by kinetic studies at elevated humidity. The rate dependence on humidity stems from moisture facilitated rearrangements on the surface of isoniazid crystallites, which lead to cocrystallization in the presence of benzoic acid vapor. Furthermore, premilling the mixture of the cocrystal ingredients eliminated the induction time of the reaction and considerably increased its rate.
authors.affiliation: †Department of Chemistry, University of Latvia, K.Valdemara street 48, Riga LV1013, Latvia.|‡School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Inese
authors.initials: I
authors.lastname: Sarceviča
authors.affiliation: †Department of Chemistry, University of Latvia, K.Valdemara street 48, Riga LV1013, Latvia.
authors.forename: Liana
authors.initials: L
authors.lastname: Orola
authors.affiliation: ‡School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Karol P
authors.initials: KP
authors.lastname: Nartowski
authors.affiliation: ‡School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Yaroslav Z
authors.initials: YZ
authors.lastname: Khimyak
authors.affiliation: ‡School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Round
authors.affiliation: ‡School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: László
authors.initials: L
authors.lastname: Fábián
mesh_terms: D019817:Benzoic Acid / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D007538:Isoniazid / Q000737:chemistry*; D007700:Kinetics; D012995:Solubility; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D019817:Benzoic Acid; D007538:Isoniazid
keywords: Cocrystallization; effect of spinning; mechanochemistry; solid-state kinetics; spontaneous reactions