Continuous, simultaneous cocrystallization and formulation of Theophylline and 4-Aminobenzoic acid pharmaceutical cocrystals using twin screw melt granulation

Eur J Pharm Sci. 2019 Sep 1;137:104981. doi: 10.1016/j.ejps.2019.104981. Epub 2019 Jul 8.


In this work a cocrystal of Theophylline and 4Aminobenzoic acid was successfully produced and formulated using a hydrophilic binder with a novel continuous melt granulation approach. This melt granulation was followed with direct compression to generate oral solid dosage forms. The study revealed that the processing temperature, molecular weight of the binder and binder concentration were the most effective parameters for the production and formulation of high purity cocrystals. Superior tableting performance was observed for melt granulated cocrystals as compared with extruded cocrystals and pure theophylline. Moreover the prepared THP-4ABA melt granulated cocrystals were stable for 14 days (50 °C and 75% RH).

Keywords: Continuous cocrystallization; Formulation; Material properties; Stability studies; Theophylline/4 aminobenzoic cocrystals; Twin screw melt granulation.

MeSH terms

  • 4-Aminobenzoic Acid / chemistry*
  • Crystallization
  • Polyethylene Glycols / chemistry
  • Tablets
  • Technology, Pharmaceutical
  • Temperature
  • Theophylline / chemistry*


  • Tablets
  • Polyethylene Glycols
  • Theophylline
  • 4-Aminobenzoic Acid