A novel insulin microcrystals preparation using a seed zone method

Jai Hyun Kwon, Chan Wha Kim

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Milling and supercritical fluid technology have been used to prepare particles suitable for pulmonary delivery, but problems remain, e.g., the loss of protein activity, the heterogeneity of drug particles including shape, size etc., process yield, and the applicability for industrial production process. Therefore, in order to develop a novel process for particle preparation, crystallization was investigated using insulin as a model protein. The relation between the number of seed particles and the final crystal size was investigated, and a novel microcrystallization process, named "seed zone" method, was developed. The size of crystals was inversely proportional to the number of seeds in crystallizing solution. Spontaneous crystallization occurred around pH 6 in acetic acid solution, however, more than 60% of crystals were bigger than 5μm with two peak size distributions. On the contrary, microcrystals with a mean diameter of 3μm were prepared using a seed zone method. The "seed zone" is a pH range where the seed particles are stable in crystallizing solution. Almost 90% (in volume) of microcrystals were under 5μm, and the yield of crystallization was maintained at 90% or higher. In the seed zone, nano-sized particles (96nm) with narrow size distributions were identified. Therefore, it is likely that these nano-sized particles would be used as seeds in microcrystals formation. It is suggested that insulin microcrystallization using a seed zone could be a useful particle preparation process in pharmaceutical industry.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalJournal of Crystal Growth
Issue number1-4
Publication statusPublished - 2004 Mar 1


  • A1. Biocrystallization
  • A2. Growth from solutions
  • A2. Industrial crystallization
  • A2. Seed crystals
  • B1. Insulin

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Inorganic Chemistry
  • Materials Chemistry


Dive into the research topics of 'A novel insulin microcrystals preparation using a seed zone method'. Together they form a unique fingerprint.

Cite this