Baclofen (BAC) is
an important chiral active pharmaceutical ingredient
for the treatment of specific neurological disorders that is commercially
available only as RS-BAC (racemate). Using the liquid-assisted
grinding technique, combination of RS-BAC with DL-MA in 1:1 stoichiometric ratio yielded a crystalline
solid phase mixture of the enantiomeric salts R-BAC:L-MA and S-BAC:D-MA. Single-crystals
suitable for SCXRD analysis of R-BAC:L-MA were obtained by fractional crystallization from a solution of RS-BAC and L-MA in a solvent mixture of
ethyl acetate and water. Analysis of the supramolecular interaction
patterns revealed that the crystal structure is stabilized by strong
N+–H···–O, N+–H···O and O–H···–O hydrogen-bonding interactions. A comparative study
with structurally related compounds enabled to identify common homo-
and heterosynthons involving RNH3
+, OH, and
COOH/COO– groups. The spectroscopic, structural
and thermogravimetric studies of the enantiomeric solid phase mixture
of R-BAC:L-MA and S-BAC:D-MA was accomplished by examination of some
basic pharmaceutically relevant physicochemical properties. Phase
stability studies in aqueous media simulating the gastrointestinal
tract physiological conditions (pH 1.2 and 4.5) showed that R-BAC:L-MA/S-BAC:D-MA transforms into BAC within a few minutes. However,
upon exposure to standard thermal/humidity stress conditions, the
phases were stable. The decomposition changes the kinetics of the
dissolution process under sink conditions, but the calculated intrinsic
dissolution rates of RS-BAC and R-BAC:L-MA/S-BAC:L-MA resulted to be quite similar.
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