Mixture design applied to optimize a directly compressible powder produced via cospray drying.
ABSTRACT Coprocessing via spray drying was applied to improve the compactability of acetaminophen and to select an optimal formulation. Four-component mixtures containing acetaminophen, mannitol, erythritol, and maltodextrin were produced by cospray drying. A D-optimal mixture design was constructed to evaluate the spray dried powder and tablet properties. An increasing mannitol and erythritol content improved powder flowability and density. However, a higher erythritol concentration in the spray dried powder mixture had a negative influence on tablet tensile strength and friability. A higher maltodextrin content increased tablet tensile strength and improved tablet friability, while disintegration time, average particle size, powder flowability, density, and hygroscopicity were negatively influenced.
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ABSTRACT: Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility, powder hygroscopicity, flowability, and compactability. The influence of process parameters during spray drying on the compaction behaviour of drug/excipient mixtures was investigated via Heckel analysis. Erythritol, lactose, maltodextrin, and mannitol were efficient in co-spray drying with acetaminophen. However, lactose mixtures showed poor flowability. Spray dried mixtures containing mannitol and erythritol were characterised as non-hygroscopic, highly dense, and good flowing powders. Mannitol increased tablet tensile strength in contrast with the poor compactability of erythritol. Maltodextrin was selected for further experiments because it provided excellent tablet tensile strength. The use of erythritol, maltodextrin and mannitol in binary drug/excipient mixtures resulted in high process yields. Compacts of erythritol, mannitol, and maltodextrin were characterised by higher tablet tensile strength at higher spray drying temperatures due to the increased particle fragmentation of erythritol and mannitol mixtures and to the increased plastic deformation of maltodextrin formulations. A combination of erythritol, maltodextrin, and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression.European Journal of Pharmaceutics and Biopharmaceutics 09/2007; 67(1):220-6. · 3.83 Impact Factor
- Spray drying in practice..
Faculty of Pharmaceutical Sciences
Coprocessing via spray drying
as a formulation platform
the compactability of various
Thesis submitted to obtain the degree of
Doctor in Pharmaceutical Sciences
Prof. Dr. Apr. Jean-Paul Remon
Prof. Dr. Apr. Jean-Paul Remon
Prof. Dr. Apr. Chris Vervaet
Laboratory of Pharmaceutical Technology
The author and the promoters give the authorisation to consult and to copy parts of this thesis
for personal use only. Any other use is limited by the Laws of Copyright, especially
concerning the obligation to refer to the source whenever results are cited from this thesis.
Gent, 17 December 2008
Prof. Dr. Apr. Jean-Paul Remon & Prof. Dr. Apr. Chris Vervaet Yves Gonnissen