Table 1. Summary of Salts and Cocrystals and the Physicochemical Properties of PRM, MEL, LRM, and TNM.

name	system	multicomponent formers	physicochemical propertiesa
PRM	salt/salt solvate	4-aminopyridine, 4-dimethylaminopyridine, piperazine (this work)	higher solubility at pH 6.5, modified luminescence
		l-arginineb,33	higher solubility in H2O, greater bioavailability (x 1.38)
		ethanolamine,b diethanolamine,b triethanolamineb21	no improvement in solubility at pH 1.2, higher bioavailability and solubility at pH 6.8
		norfloxacin MeOH34	higher solubility at pH 6.8 (x 1.4)
	cocrystal/cocrystal solvate	benzoic acid35	increased solubility (x 3), increased dissolution rate in H2O (x 2) improved oral bioavailability in rats (x 15)
		clonixin ethyl acetate36	improved moisture stability
		febuxostat37	improved dissolution at pH 6.8 (x 2.8), improved flow and compressibility
		ferulic acid38	improved IDR at pH 2 (x 1.7), improved powder flowability
		furosemide39	good thermal stability, good stability under accelerated aging
		nicotinamide,b resorcinol,b saccharin sodium,b ureab,40	no solubility advantage
		methylparaben,b vanillinb,41	no solubility and IDR advantages at pH 1.2, superior dissolution rates in the sink condition at pH 1.2
		saccharin42	reduced plasticity and significantly deteriorated tableting behavior
		sodium acetateb,40	improved solubility (x 5), improved flow and compressibility
MEL	salt/salt solvate	4-aminopyridine, 4-dimethylaminopyridine, piperazine (this work)	higher solubility at pH 6.5
		arginineb,43,44	improved dissolution behavior at pH 1.2 (x 9.4) and 7.5
		ciprofloxacin MeCN34	higher solubility at pH 6.8 (x 3)
		cysteine,b glycineb,43	improved dissolution behavior at pH 7.5
		meglumineb,45	improved solubility at pH 6
		KOH H2Ob,46	improved dissolution behavior at pH 5.6, no bioavailability advantage in vivo
		di-/triethanolamine,b tris(hydroxymethyl)aminomethane,b KOHb,44	improved dissolution behaviors at pH 1.2 (x 3.7–7.2)
	salt cocrystal	l-malic acid19,30	no solubility advantage at pH 6.5, improved bioavailability (x 1.2)
	cocrystal/cocrystal solvate	adipic acid30,47	no solubility advantage at pH 6.8
		Aspirin48	improved solubility at pH 7.4 (x 44), improved bioavailability (x 4.4)
		benzoic acid,19,49 4-hydroxybenzoic acid,b,19,30 1-hydroxy-2-naphthoic acid,19,30dl-malic acid,b,19,30,50 salicylic acid,19 succinic acid19,30,47	higher solubility at pH 6.5, improved bioavailability (x 1.1–1.6)
		(+)-camphoric acidb,30	no solubility advantage at pH 6.5
		fumaric acid19,30,50	higher solubility at pH 6.5 and 6.7, no bioavailability advantage
		glutaric acid19,30	no solubility advantage at pH 6.5, improved bioavailability (x 1.2)
		glycolic acidb,19,30	no solubility advantage at pH 6.5, no bioavailability advantage
		hydrocinnamic acidb,19,30	higher solubility at pH 6.5, no bioavailability advantage
		maleic acidb,19,30,51	higher solubility at pH 1.6, 5.0, and 6.5, improved bioavailability (x 1.2)
		salicylic acid30,50−52	higher solubility at pH 1.6, 5.0, and 6.5, enhanced drug permeation coefficient
		terephthalic acid47	higher solubility at pH 6.8
LRM	salt/salt solvate	HCl, methanesulfonic acid, NH3, piperazine,31	improved dissolution at pH 7 (x 1.3–1.6)
		norfloxacin H2O MeOH34	improved dissolution at pH 6.8 (x 1.6)
	cocrystal/cocrystal solvate	ascorbic acid,b benzoic acid,b cinnamic acid,b citric acid,b fumaric acid,b glutaric acid,b hippuric acid,b malonic acid,b salicylic acid,b succinic acid,b tartaric acidb,53	no solubility advantage in H2O
		4-aminobenzoic acid,b anthranilic acid,b ferulic acid,b 4-hydroxy benzoic acid,b oxalic acid,b resorcinol,b saccharin sodium,b ureab,53	improved solubility in H2O (x 1.6–6.9)
		1,3-dimethyl ureab,54	increased IDR at pH 1.2 (x 28) and 7.4 (x 19), improved tabletability (x 2.5) and bioavailability(x 2.5)
TNM	salt/salt solvate	ciprofloxacin MeOH34	improved dissolution at pH 6.8 (x 1.1)
		HCl, methanesulfonic acid32	no solubility and IDR advantages at pH 7
		piperazine32	improved solubility (x 5.5) and IDR (x 2.5) at pH 7
	cocrystal/cocrystal solvate	benzoic acid32	no solubility advantage, improved IDR (x 2) at pH 7
		catechol, pyrogallol, resorcinol32	improved solubility (x 5.8–10.1) and IDR(x 2.4–4.2) at pH 7
		glycolic acid,b saccharin,b salicylic acid,b succinic acid,b,55	no IDR advantage at pH 4.5 and 6.8
		salicylic acid32	no solubility and IDR advantages at pH 7

^aNo reported physicochemical properties of multicomponent forms for PRM,^{20,28,36,56,57} MEL,^27,30,58 and TNM.⁵⁵

^bNo crystal structure reported.