Interaction Studies Between Levodopa and Different Excipients to Develop Coground Binary Mixtures for Intranasal Application

Tamás Kiss, Tünde Alapi, Gábor Varga, Csilla Bartos, Rita Ambrus, P. Szabó-Révész, Gábor Katona

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Levodopa (LEVO) as the gold standard in the treatment of Parkinson's disease is usually administrated per os but its bioavailability is low. The intranasal administration is a potential alternative route to increase bioavailability of the drug and treat the off period. Our aim was to develop LEVO-containing binary nasal powders with different excipients by dry cogrinding process. The interactions between the components were examined. The optimized cogrinding process parameters (LEVO:excipient ratio and grinding time) resulted in the desired particle size range (5-40 μm). The α-cyclodextrin and poly(vinylpyrrolidone) (PVP) had an intensive crystallinity degree reducing effect on LEVO measured by XRPD, and they functioned as cogrinding agents. Hydroxypropyl methylcellulose, poly (vinyl alcohol) (PVA), and D-mannitol associate around the LEVO crystals preventing its crystalline structure. Hydrogen bonding was detected only for LEVO-PVP and LEVO-D-mannitol used Fourier-transformed infrared spectroscopy. Chemical degradation of LEVO in the products was not detected even after the accelerated stability test. The dissolution profile of the products can be characterized by the first-order kinetic model with different dissolution rate. The dissolution rate of LEVO was increased with α-cyclodextrin and PVP, and the drug release decreased in the case of hydroxypropyl methylcellulose, PVA, and D-mannitol compared to the LEVO powder.

Original languageEnglish
JournalJournal of pharmaceutical sciences
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Excipients
Levodopa
Mannitol
Cyclodextrins
Powders
Biological Availability
Intranasal Administration
Hydrogen Bonding
Nose
Particle Size
Parkinson Disease
Spectrum Analysis
Alcohols

Keywords

  • binary system
  • cogrinding
  • dissolution
  • drug-excipient interaction(s)
  • HPLC
  • levodopa
  • nasal drug delivery
  • nasal powder
  • preformulation

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Interaction Studies Between Levodopa and Different Excipients to Develop Coground Binary Mixtures for Intranasal Application. / Kiss, Tamás; Alapi, Tünde; Varga, Gábor; Bartos, Csilla; Ambrus, Rita; Szabó-Révész, P.; Katona, Gábor.

In: Journal of pharmaceutical sciences, 01.01.2019.

Research output: Contribution to journalArticle

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