☆ 4.1 Article

From a binary salt to salt co-crystals of antibacterial agent lomefloxacin with improved solubility and bioavailability

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS (2015)

Journal

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS

Volume 71, Issue -, Pages 437-446

Publisher

INT UNION CRYSTALLOGRAPHY

DOI: 10.1107/S2052520615011191

Keywords

cocrystallization; salt co-crystals; active pharmaceutical ingredients (APIs); lomefloxacin; solubility

Funding

National Natural Science Foundation of China [21201026]
Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology [BM2012110]
Qing Lan Project
Natural Science Fund for Colleges and Universities in the Jiangsu Province [12KJB150002]

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

The cocrystallization of lomefloxacin (Lf) with barbituric acid (HBA) and/or isophthalic acid (H(2)ip) leads to novel binary and ternary salts via hydrogenbonding recognition. X-ray single-crystal diffraction analyses show that zwitterionic lomefloxacin can adjust itself to fulfill a different supramolecular array in either binary salts or ternary salt co-crystals, formulated as [HLf]center dot[Hip]center dot H2O (1), [HLf]center dot[BA]center dot[HBA]center dot H2O (2) and [HLf]center dot[BA]center dot[H(2)ip]center dot CH3OH center dot H2O (3). These pharmaceutical agents present uniform charge-assisted hydrogen-bonding networks between HLf cations and acidic coformers with the lattice capturing water molecules. Structural comparison of (2) and (3) indicated that a delicate balance of geometries and hydrogenbonding partners is required for stacking to favor the formation of ternary salt co-crystals. Cocrystallization was able to overcome the water insolubility of lomefloxacin. Both the salt co-crystals display enhanced solubility and better pharmaceutical applicability.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.1

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Cocrystallization of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicines

Hongjie Guo, Shuyu Liu

Summary: This review summarizes the cocrystals of active pharmaceutical ingredients (APIs) derived from traditional Chinese medicines (TCMs) in terms of categories, Delta pKa rule, preparation, characterization, and physicochemical properties based on 113 literature reports. The formation of all cocrystals is found to be in accordance with Delta pKa rule. The most commonly used preparation methods are evaporation cocrystallization, grinding method, and suspension method, accounting for 44%, 27%, and 16% respectively. Almost all cocrystals are characterized by powder X-ray diffraction (PXRD). Thermal analysis techniques are used for 81% of cocrystals, and more than half of them are characterized by IR. Single crystal X-ray diffraction (SXRD) is used for 44% of cocrystals due to difficulties in obtaining single crystal samples. Most cocrystals of APIs in TCMs exhibit 1-10 folds enhancement in solubility, dissolution, dissolution rate, and bioavailability, with some showing even greater improvements. This review serves as a valuable reference for future pharmaceutical cocrystals of APIs in TCMs.

CHEMICAL & PHARMACEUTICAL BULLETIN (2023)