(316a) Formation of Poly(?-caprolactone) Nanoparticles in Microstructured Mixers Via Solvent Replacement Precipitation: Fundamental Studies and Scale-Up Concepts

Poly(ε-caprolactone) nanoparticles are frequently employed in pharmaceutics for controlled drug release [1] and are often obtained via solvent replacement precipitation [2]. With microstructured mixers these particles were obtained free from mixing influences during their formation (size app. 100 - 500 nm). This is shown by two different approaches: 1.) the variation of the feed rates shows no influence on the particle size distribution. 2.) precipitation with different mixers (cyclone mixers [3] and multilamination mixers [4]), which could be clearly distinguished regarding their ‘mixing qualities’ using the iodide iodate reaction method, yield precipitates with the same particle size distribution. Hence, mixing in these microstructured mixers is significantly faster than the particle formation rate.

Fundamental studies:

Ruling out inhomogeneities caused by insufficient mixing, influencing factors on the particle size were examined using a microstructured cyclone mixer. With this mixer excellent mixing is obtained at low flow rates. This suggests that microstructured cyclone mixers are an effective tool for scientific research, especially when materials are expensive or difficult to obtain. Influencing factors which were identified in previous studies [2] are substantiated, namely the polymer outlet concentration and the composition of the solvent (acetone and water in different ratios). Examinations free from mixing influence allow for the quantification of these factors. It could be shown that the reproducibility increased inversely to particle size.

Scale-up concepts:

Mixing in multilamination mixers (V type and Y type) is significantly slower compared to mixing in cyclone type mixers but still significantly faster than the particle formation rate. IMVT’s multilamination mixers are constructed from stacks of micromachined foils. By stacking micromachined foils a multichannel system is obtained. Scaling of those mixers is possible by the variation of the number of micromachined foils. Constant ‘mixing qualities are obtained keeping a constant linear fluid velocity in the microchannels. The scaling concept has been investigated using the iodide iodate reaction method [4].

[1] R. Langer, Science 249 (1990) 1527-1533.

[2] F. Lince et al., Journal of Colloid and Interface Science 322 (2008) 505–515.

[3] A. Kölbl et al., Chemical Engineering Journal 167 (2011) 444–454.

[4] A. Kölbl et al., Chemical Engineering Journal 160 (2010) 865–872