Spherical crystal agglomeration of ibuprofen by the solvent‐change technique in presence of methacrylic polymers

Journal of Pharmaceutical Sciences (Impact Factor: 2.59). 02/2000; 89(2):250 - 259. DOI: 10.1002/(SICI)1520-6017(200002)89:2<250::AID-JPS12>3.0.CO;2-W


The effects of Eudragit® nature on the formation and spherical agglomeration of ibuprofen microcrystals have been examined when solvent change (ethanol-water) technique is applied. Four methacrylic polymers (Eudragit® S100, L100, RS, and RL), with different solubility and solubilizing ability, were used. The extrapolated points of maximum temperature deviation rate in crystallization liquid that reflect the maximum crystallization rate and the corresponding water addition were determined, as well as crystal yielding and incorporation of drug and polymer in the agglomerates. The physicomechanical properties of the agglomerates, such as size, sphericity, surface roughness and porosity, as well as flow and packing or compression behavior during tableting, were evaluated for different drug/polymer ratios. It was found that crystal yield is greatly reduced in the presence of water-insoluble polymers and that formation of the microcrystals and incorporation of drug and polymer are affected by the polymer nature. Crystal formation changes are attributed to alterations in the metastable zone, whereas the changes in drug and polymer incorporation and crystal yield are caused by changes in the polymers' solubility and micellization. The size of agglomerates depends on the polymer nature and its interactions with the ibuprofen microcrystals formed. Sphericity, surface roughness, and intraparticle porosity of agglomerates increase, in general, with the presence of polymer owing to changes in habit and growth rate of the microcrystals and to their coating before binding into spherical agglomerates. The particle density or intraparticle porosity and size changes determine flow or packing behavior and densification of agglomerates at low compression. The incorporation and brittleness of the polymer determine the deformation under higher compression pressure, expressed as yield pressure, Py.

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Available from: Kyriakos Kachrimanis, Nov 27, 2014
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    • "This solid dispersion might change the hydrophobic drug to a hydrophilic form, resulting in increased solubility of the poorly water-soluble drug. Since water was used as a solvent in this study, unlike traditional solid dispersion methods, this solid dispersion method has several advantages over other methods on an industrial scale, as there is no necessity to remove the organic solvent, thus respecting strict air-quality controls, reducing potential toxicity and mitigating the risk of explosion (Kachrimanis et al., 2000). The surface morphology of the RFX powder, the physical mixture and the solid dispersion formulation are shown in Fig. 7. "
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    International Journal of Pharmaceutics 01/2013; 443(1). DOI:10.1016/j.ijpharm.2013.01.013 · 3.65 Impact Factor
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    10/2012; 2(4):169-75. DOI:10.4103/2230-973X.106981
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