Mixture Design Applied to Optimize a Directly Compressible Powder Produced via Cospray Drying

Laboratory of Pharmaceutical Technology, Ghent University, Gent, Belgium.
Drug Development and Industrial Pharmacy (Impact Factor: 2.1). 04/2008; 34(3):248-57. DOI: 10.1080/03639040701542143
Source: PubMed

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: The objective of the current study was to develop and optimize a sublingual tablet formulation of captopril which is an effective drug in the treatment of hypertension. Captopril containing tablets were prepared by direct compression method using different ingredients such as polyvinyl pyrrolidone, starch 1500, sodium starch glycolate and lactose (independent variables) and magnesium stearate, talc and aspartame (fixed components). Tablets were evaluated for the physical properties including hardness, disintegration time and friability which were considered as responses in a D-optimal experimental plan. Results were statistically examined using special cubic model and polynomial mathematical equations and found to be statistically significant (p< 0.05) for disintegration time and friability data. Meanwhile linear model was best fitted with hardness data. The obtained results were used to generate optimized overlay plot. The physical data from the numerical optimization were verified and found to be very close to those predicted from the regression analysis. Additional experiments including drug content, in vitro drug dissolution rate and accelerated stability studies were also performed on the optimum formulation. All results were in accordance with the requirements of a sublingual tablet.
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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.
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