AAPS PharmSciTech

, 20:331 | Cite as

Utility of Films to Anticipate Effect of Drug Load and Polymer on Dissolution Performance from Tablets of Amorphous Itraconazole Spray-Dried Dispersions

  • Moshe Honick
  • Kanika Sarpal
  • Alaadin Alayoubi
  • Ahmed Zidan
  • Stephen W. Hoag
  • Robert G. Hollenbeck
  • Eric J. Munson
  • James E. PolliEmail author
Research Article


Because spray-dried dispersion (SDD) performance depends on polymer selection and drug load, time- and resource-sparing methods to screen drug/polymer combinations before spray drying are desirable. The primary objective was to assess the utility of films to anticipate the effects of drug load and polymer grade on dissolution performance of tablets containing SDDs of itraconazole (ITZ). A secondary objective was to characterize the solid-state attributes of films and SDDs to explain drug load and polymer effects on dissolution performance. SDDs employed three different grades of hypromellose acetate succinate (i.e., either HPMCAS-L, HPMCAS-M, or HPMCAS-H). Solid-state characterization employed differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. Results indicate that films correctly anticipated the effects of drug load and polymer on dissolution performance. The best dissolution profiles were observed under the following conditions: 20% drug loading performed better than 30% for both films and SDDs, and the polymer grade rank order was HPMCAS-L > HPMCAS-M > HPMCAS-H for both films and SDDs. No dissolution was detected from films or SDDs containing HPMCAS-H. Solid-state characterization revealed percent crystallinity and phase miscibility as contributing factors to dissolution, but were not the sole factors. Amorphous content in films varied with drug load (10% > 20% > 30%) and polymer grades (HPMCAS-L > HPMCAS-M > HPMCAS-H), in agreement with dissolution. In conclusion, films anticipated the rank-order effects of drug load and polymer grade on dissolution performance from SDDs of ITZ, in part through percent crystallinity and phase miscibility influences.


amorphous solid dispersion itraconazole spray drying dissolution hypromellose acetate succinate 



Amorphous solid dispersions


Cross-polarization magic angle spinning


Differential scanning calorimetry


Hot melt extrusion




Hypromellose acetate succinate




Loss on drying


One factor at a time


Polarized light microscopy


Powder X-ray diffraction


Relative humidity


Spray-dried dispersion


Scanning electron microscopy


Silicified microcrystalline cellulose


Sodium starch glycolate


Solid-state nuclear magnetic resonance


Glass transition temperature


Total spinning sideband suppression


Funding Information

We are grateful to the National Institute for Pharmaceutical Technology and Education (NIPTE) and the U.S. Food and Drug Administration (FDA) for providing funds for this research. This study was funded by the FDA Grant to NIPTE titled “The Critical Path Manufacturing Sector Research Initiative (U01)”; Grant# 5U01FD004275. This scientific publication reflects the views of the authors and should not be construed to represent FDA’s views or policies.

Compliance with Ethical Standards

Conflict of Interest

The authors declare the following competing financial interest(s): E.J.M. is a partial owner of Kansas Analytical Services, a company that provides solid-state NMR services to pharmaceutical companies. The results presented here are from academic work at University of Kentucky, and no data from Kansas Analytical Services are presented.

Supplementary material

12249_2019_1541_MOESM1_ESM.docx (1.6 mb)
ESM 1 (DOCX 1669 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Moshe Honick
    • 1
  • Kanika Sarpal
    • 2
  • Alaadin Alayoubi
    • 3
  • Ahmed Zidan
    • 3
  • Stephen W. Hoag
    • 1
  • Robert G. Hollenbeck
    • 1
  • Eric J. Munson
    • 2
    • 4
  • James E. Polli
    • 1
    Email author
  1. 1.Department of Pharmaceutical SciencesUniversity of Maryland School of PharmacyBaltimoreUSA
  2. 2.Department of Pharmaceutical SciencesUniversity of Kentucky College of PharmacyLexingtonUSA
  3. 3.Food and Drug AdministrationSilver SpringUSA
  4. 4.Department of Industrial and Physical PharmacyPurdue University College of PharmacyWest LafayetteUSA

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