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Int J Pharm. 2014 Apr 10;464(1-2):34-45. doi: 10.1016/j.ijpharm.2014.01.013. Epub 2014 Jan 19.

Formulation parameters of crystalline nanosuspensions on spray drying processing: a DoE approach.

Author information

  • 1University of Connecticut, School of Pharmacy, Storrs, CT 06269, USA.
  • 2AbbVie Pte Ltd, Research and Development, 11 Biopolis Way, Helios, #05-06, Singapore 138667, Singapore.
  • 3University of Connecticut, School of Pharmacy, Storrs, CT 06269, USA. Electronic address: d.burgess@uconn.edu.

Abstract

Nanocrystalline suspensions offer a promising approach to improve dissolution of BCS class II/IV compounds. Spray drying was utilized as a downstream process to improve the physical and chemical stability of dried nanocrystals. The effect of nanocrystalline suspension formulation variables on spray-drying processing was investigated. Naproxen and indomethacin nanocrystalline formulations were formulated with either Dowfax 2A1 (small molecule) or HPMC E15 (high molecular weight polymer) and spray drying was performed. A DoE approach was utilized to understand the effect of critical formulation variables, i.e. type of stabilizer, type of drug, ratio of drug-to-stabilizer and drug concentration. The powders were analyzed for particle size, moisture content, powder X-ray diffraction and dissolution. A dialysis sac adapter for USP apparatus II was developed which provided good discrimination between aggregated and non-aggregated formulations. Nanocrystal aggregation was dependent on the drug-to-stabilizer ratio. The glass transition temperature and the charge effect played a dominant role on spray-dried powder yield. Those formulations with low drug-to-excipient ratios were less aggregating and showed faster dissolution compared to those formulations with high drug-to-excipient ratios. All stable (less aggregated) formulations were subjected to accelerated storage stability testing. The Flory-Huggins interaction parameter (between drug and excipients) correlated with the spray-dried nanocrystal formulations stability.

Published by Elsevier B.V.

KEYWORDS:

DoE; Nanocrystalline; Nanosuspension; Re-dispersion; Spray drying

PMID:
24447788
[PubMed - indexed for MEDLINE]
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