Design Space and QbD Approach for Production of Drug Nanocrystals by Wet Media Milling Techniques

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Abstract

Drug nanocrystals are nanosized solid drug particles, the most important application of which is the improvement of solubility properties of poorly soluble drug materials. Drug nanocrystals can be produced by many different techniques, but the mostly used are different kinds of media milling techniques; in milling, particle size of bulk sized drug material is decreased, with the aid of milling beads, to nanometer scale. Utilization of Quality by Design, QbD, approach in nanomilling improves the process-understanding of the system, and recently, the number of studies using the QbD approach in nanomilling has increased. In the QbD approach, the quality is built into the products and processes throughout the whole production chain. Definition of Critical Quality Attributes, CQAs, determines the targeted final product properties. CQAs are confirmed by setting Critical Process Parameters, CPPs, which include both process parameters but also input variables, like stabilizer amount or the solid state form of the drug. Finally, Design Space determines the limits in which CPPs should be in order to reach CQAs. This review discusses the milling process and process variables, CPPs, their impact on product properties, CQAs and challenges of the QbD approach in nanomilling studies.
Original languageEnglish
Article number104
JournalPharmaceutics
Volume10
Issue number3
Number of pages17
ISSN1999-4923
DOIs
Publication statusPublished - 25 Jul 2018
MoE publication typeA2 Review article in a scientific journal

Fields of Science

  • 317 Pharmacy
  • drug nanocrystals
  • wet media milling
  • Quality by Design (QbD)
  • Critical Quality Attributes (CQA)
  • process variables
  • PARTICLE-SIZE REDUCTION
  • POORLY SOLUBLE DRUGS
  • HIGH-PRESSURE HOMOGENIZATION
  • CRITICAL QUALITY ATTRIBUTES
  • CRITICAL PROCESS PARAMETERS
  • IN-VIVO EVALUATION
  • ORAL BIOAVAILABILITY
  • NANOSUSPENSION
  • FORMULATION
  • OPTIMIZATION

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