Evaluation of Different Techniques for Size Determination of Drug Nanocrystals: A Case Study of Celecoxib Nanocrystalline Solid Dispersion

• Main Authors: Amanpreet Kaur, Prashantkumar Khodabhai Parmar, Arvind Kumar Bansal
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Pharmaceutics
• Subjects: celecoxib; nanocrystalline solid dispersion; agglomerates; aggregates; discriminatory dissolution testing
• Online Access: https://www.mdpi.com/1999-4923/11/10/516

Celecoxib (CEL) Nanocrystalline Solid Dispersion (CEL_NCSD) was generated by spray drying CEL, mannitol (MAN) and sodium lauryl sulfate (SLS) from a solvent mixture of methanol, acetone and water. The purpose of the work was to determine the size of CEL nanocrystals, investigate agglomeration and inspect dissolution of CEL_NCSD. Size determination was challenging as CEL nanocrystals are embedded in the matrix of MAN. Firstly, neat CEL_NCSD was analyzed using Scherrer equation. Secondly, MAN was dissolved in an aqueous stabilizer medium to selectively measure the size of CEL nanocrystals. Raman Spectra captured in Morphologi G3-ID confirmed the presence of CEL-only particles in the media. This dispersion gave D₉₀ values of 882 ± 170.34 nm in Zetasizer. Discriminatory dissolution studies confirmed total release of 34.61 ± 1.59%, 47.42 ± 0.24%, and 44.61 ± 1.11% at 120 min from a microsuspension (size 3 µm), a nanosuspension (media milled; size 660 nm) and CEL_NCSD, respectively. The dissolution profile of CEL_NCSD was similar to that of a nanosuspension (f2 72.24) instead of a coarse microsuspension. Thus, the present study revealed that optimized sample preparation is critical for the size determination of embedded drug nanocrystals in NCSD. Further, a discriminatory dissolution study substantiated that the size of CEL nanocrystals in CEL_NCSD is well below 1000 nm, thus showing a size-dependent improved dissolution profile.