お問い合わせ03(3790)8011

最新情報

2014/1/7
Milling of poorly water-soluble drug down to the nano size for solubility enhancement

In recent years, many of newly-developed pharmaceutical drugs are poorly soluble in water. These drugs are difficult to be absorbed into the body, therefore the enhancement of the solubility is required. Out of the various methods for solubility enhancement, decreasing the particle size by milling is one of the methods.
In general, it is said that wet milling is possible to mill materials to finer particle size than by dry milling. Using NARA’s MICROS, we have milled powder to the nano-scale with water as the medium. In recent research, it has turned out that milling to the nano-scale can be performed by adding various additives. Here is an example which we used phospholipid polymer aqueous solution as a grinding medium.
Ibuprofen (45g) having the average particle size of 25 micrometer and phospholipid polymer aqueous solution, in which concentration was varied, were milled by MICROS (rotating speed 2000rpm, 15min). Each material’s particle size distribution and dissolution behavior are shown in Figure 1 and 2.
The particle size distributions were measured by laser diffraction particle size analyzer (SALDA-2100 SHIMADZU), and the dissolution test were performed based on the Japanese Pharmacopoeia.
By milling with the MICROS, ibuprofen was milled below 1 micrometer. Ibuprofen with more than 2wt% phospholipid polymer had the average particle size of 128nm. Also the particle size distribution was very sharp. Compared with the raw material, the milled products increased its dissolution properties. Especially when the phospholipid polymers were added, almost 100% dissolution was obtained within 5 minutes.
From the above results, the dissolution of ibuprofen was improved by decreasing the particle size, thus increasing the surface area by milling. Additionally, the hydrophobic group of the phospholipid polymer binds to the surface of the ibuprofen and the hydrophilic group faces towards the surrounding water, therefore the affinity with water was increased, which also contributes to the solubility enhancement.
 The MICROS has various results not only in pharmaceutical materials, but also in electronic industry, food, pigments, etc. Please do not hesitate to contact us.

(Osaka Prefecture University, S. Watano, Parmaceuticals and Particle Design Symposium 2011)
Fig. 1 Particle size distribution of ibuprofen
Fig. 2 Dissolution property of ibuprofen