Polymer/Amorphous Salt Solid Dispersions of Ciprofloxacin

Abstract

Purpose

To improve the pharmaceutical properties of amorphous ciprofloxacin (CIP) succinate salts via formulation as polymer/amorphous salt solid dispersions (ASSDs).

Methods

ASSDs consisting of an amorphous CIP/succinic acid 1:1 or 2:1 salt dispersed in PVP or Soluplus were produced by spray drying and ball milling. The solid state characteristics, miscibility, stability, solubility and passive transmembrane permeability of the ASSDs were then examined.

Results

The ASSDs had higher glass transition and crystallization temperatures than the corresponding amorphous succinate salts, and were also more stable during long-term stability studies. The results of inverse gas chromatography and thermal analysis indicated that the salts and polymers form a miscible mixture. The solubility of the pure drug in water and biorelevant media was significantly increased by all of the formulations. The permeability of the ASSDs did not differ significantly from that of the amorphous CIP succinate salts, however all samples were less permeable than the pure crystalline drug.

Conclusions

The formulation of amorphous CIP succinate salts as ASSDs with polymer improved their long-term stability, but did not significantly affect their solubility or permeability.

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Abbreviations

ASD:

Amorphous solid dispersion

ASSD:

Amorphous salt solid dispersion

BM:

Ball milled

CIP:

Ciprofloxacin

CS 1:1:

Ciprofloxacin hemisuccinate (ciprofloxacin/succinic acid 1:1)

CS 2:1:

Ciprofloxacin succinate (ciprofloxacin/succinic acid 2:1)

G-T:

Gordon-Taylor

SD:

Spray dried

PAMPA:

Parallel artificial membrane permeability assay

PM:

Physical mixture

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Correspondence to Lidia Tajber.

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Mesallati, H., Tajber, L. Polymer/Amorphous Salt Solid Dispersions of Ciprofloxacin. Pharm Res 34, 2425–2439 (2017). https://doi.org/10.1007/s11095-017-2250-z

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Keywords

  • Ciprofloxacin
  • amorphous salt solid dispersion
  • stability
  • solubility
  • permeability