The solid-state continuum: a perspective on the interrelationships between different solid-state forms in drug substance and drug product

Abstract

Objective The objective of the review is to provide an overview of the nomenclature used in the solid-state continuum and relate these to the development of drug substances and drug products. Key findings The importance of a rational approach to solid-state form selection, including integrated decision making (ensuring equal weight is given to the needs of the drug substance and the drug product), is vital for the effective development of a drug candidate. For example, how do secondary processing considerations influence the selection of drug substance solid-state form and resulting formulation, and how can drug substance solid-state form be used to optimise secondary processing? Further, the potential use of 'crystal' engineering to optimise stability, purity and optical resolutions, and the linked regulatory requirements, will be discussed. Summary The nomenclature used in the solid-state continuum, which contains a large number of different crystalline and non-crystalline forms, for example, amorphous systems, was reviewed. Further, the significant role of the drug substance within the solid oral dose form from a physicochemical perspective was covered.

In-vitro evaluation of performance of solid immediate release dosage forms of weak bases in upper gastrointestinal lumen: experience with miconazole and clopidogrel salts

“…These data are in line with a previous study according to which the use of doxazosin salts was not advantageous in regard to absorption kinetics of doxazosin. [26] Although salt formation is a well-known technique for modifying and optimizing the physicochemical properties of an ionizable compound, for example hygroscopicity, stability, and impurity profiles, [1] published information [16,17,26] and data from this study raise concerns on their usefulness in improving luminal performance of APIs with weakly alkaline properties.…”

“…Miconazole nitrate π ± SD σ ± SD π ± SD σ ± SD 0-15 0.16 ± 0.07 a −0.28 ± 0.05 b 0.55 ± 0.01 a 0.15 ± 0.29 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] 0.19 ± 0.08 a −0.39 ± 0.02 b 0.51 ± 0.0 a 0.12 ± 0.58 [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] 0.07 ± 0.02 a −0.63 ± 0.02 b 0.26 ± 0.02 a 0.87 ± 0.81 SD, standard deviation. a Significantly higher than zero (P-value <0.05).…”

“…Based on data from preclinical species, salts can substantially improve oral absorption characteristics of weakly alkaline compounds [12–15]. Surprisingly, however, human data are very limited, if any,[16,17] unlike human data indicating the usefulness of salts in improving oral absorption characteristics of weak acids [18–20]…”

“…[10] Based on data from preclinical species, salts can substantially improve oral absorption characteristics of weakly alkaline compounds. [12][13][14][15] Surprisingly, however, human data are very limited, if any, [16,17] unlike human data indicating the usefulness of salts in improving oral absorption characteristics of weak acids. [18][19][20] The objective of this investigation was to evaluate the impact of the administered chemical form of APIs with weakly alkaline characteristics, that is salt and counterion identity, on performance of immediate release solid dosage forms in upper gastrointestinal lumen by using in-vitro methodologies.…”

In silico screening of dicarboxylic acids for cocrystallization with phenylpiperazine derivatives based on both cocrystallization propensity and solubility advantage

“…For example, the statistical analysis of large populations of binary systems allows the classification of coformer properties that promote cocrystal formation [29, 30]. Furthermore, the role of intermolecular interactions in the formation of supramolecular patterns [31, 32] in single-component and multicomponent solids has been established in the literature through the introduction of the term “synthon” [33]. Alternatively, some methods that consider the electrostatic potential surface of the molecule have been used to identify the most likely contacts between components [24, 34, 35].…”