Novel Salt-Cocrystals of Berberine Hydrochloride with Aliphatic Dicarboxylic Acids: Odd-Even Alternation in Physicochemical Properties

Mol Pharm. 2021 Apr 5;18(4):1758-1767. doi: 10.1021/acs.molpharmaceut.0c01250. Epub 2021 Mar 3.

Abstract

In this study, various structurally similar aliphatic dicarboxylic acids, namely, succinic acid, glutaric acid, adipic acid, and pimelic acid, were employed as coformers to obtain phase pure cocrystals with berberine chloride (BCl) by a slow solvent evaporation method. The structures of the four novel salt-cocrystals of BCl were determined by single crystal X-ray diffraction analysis and their solid-state properties were characterized. Compared with BCl·2H2O, all the cocrystals showed a higher melting point, improved powder dissolution and intrinsic dissolution rate (IDR), and lower hygroscopicity. It is noteworthy that the melting points and IDRs of these cocrystals exhibit an odd-even alternation with the carbon chain length of the acids.

Keywords: aliphatic dicarboxylic acids; berberine chloride; intrinsic dissolution rate; melting point; odd−even alternation; salt-cocrystals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Berberine / administration & dosage
  • Berberine / chemistry
  • Berberine / pharmacokinetics*
  • Biological Availability
  • Calorimetry, Differential Scanning
  • Chemistry, Pharmaceutical
  • Dicarboxylic Acids / chemistry*
  • Drug Compounding / methods
  • Drug Liberation
  • Excipients / chemistry*
  • Hydrogen Bonding
  • Powder Diffraction
  • Solubility

Substances

  • Dicarboxylic Acids
  • Excipients
  • Berberine