Stable solid dispersion of lurasidone hydrochloride with augmented physicochemical properties for the treatment of schizophrenia and bipolar disorder

Biopharm Drug Dispos. 2020 Nov;41(8-9):334-351. doi: 10.1002/bdd.2252. Epub 2020 Nov 5.

Abstract

Crystalline solid dispersion of lurasidone hydrochloride (LH) was made with various polar and non-polar small molecules to overcome the poor aqueous solubility issue. LH-Glutathione (GSH) solid dispersion in 1:1 ratio was prepared by co-grinding method and characterized by using differential scanning calorimetry (DSC), powder X-ray diffraction, Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy. GSH acts as antioxidant and reported for anti-schizophrenic activity may provide synergistic action with LH or reduce the side effects. LH in LH-GSH solid dispersion (SD) has shown improvement in solubility by 7.9 folds than plain drug which translated in terms of improved dissolution rate by two-folds. The in vitro dissolution results showed maximum dissolution rate with LH-GSH SD (97.85 ± 2.40%) compared to plain drug (50.5 ± 3.02%) at 15 min (t15 min, %) and thus, satisfying criteria of immediate release dosage form. DSC and FTIR data confirmed the stability of LH-GSH SD for 3 months at accelerated stability condition (40 ± 2°C and 75 ± 5% RH). The prepared LH-GSH SD can be used as a tool to target dual problems that is, enhanced physicochemical properties along with possible management of disorder which could be due to synergism with co-administered GSH. This approach is thought to be efficiently providing the relief to the psychological patients.

Keywords: anti-psychotic; antioxidant; equilibrium solubility; in vitro dissolution; lurasidone hydrochloride; solid dispersion.

MeSH terms

  • Antipsychotic Agents / chemistry*
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Drug Carriers / chemistry
  • Drug Liberation
  • Drug Stability
  • Lurasidone Hydrochloride / chemistry*
  • Lurasidone Hydrochloride / therapeutic use
  • Schizophrenia / drug therapy
  • Solubility
  • Suspensions

Substances

  • Antipsychotic Agents
  • Drug Carriers
  • Suspensions
  • Lurasidone Hydrochloride