Research Article Utility of Films to Anticipate Effect of Drug Load and Polymer on Dissolution Performance from Tablets of Amorphous Itraconazole Spray-Dried Dispersions 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 and James E. Polli 1,5 Received 11 June 2019; accepted 16 September 2019 Abstract. 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. KEY WORDS: amorphous solid dispersion; itraconazole; spray drying; dissolution; hypromellose acetate succinate. INTRODUCTION As a large number of molecules with poor water solubility enter the drug development pipeline, there is an increasing need for formulation strategies that maximize oral drug bioavailability and enable development into viable drug products (1). One such strategy is to formulate poorly soluble drug in its more energetic amorphous state, rather than in its Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-019-1541-6) contains supplementary material, which is available to authorized users. 1 Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland 21201, USA. 2 Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536, USA. 3 Food and Drug Administration, Silver Spring, Maryland 20993, USA. 4 Present Address: Department of Industrial and Physical Pharmacy, Purdue University College of Pharmacy, West Lafayette, Indiana 47907, USA. 5 To whom correspondence should be addressed. (e–mail: jpolli@rx.umaryland.edu) Abbreviations: ASD, Amorphous solid dispersions; CP/MAS, Cross- polarization magic angle spinning; DSC, Differential scanning calorimetry; HME, Hot melt extrusion; HPMC, Hypromellose; HPMCAS, Hypromellose acetate succinate; ITZ, Itraconazole; LOD, Loss on drying; OFAT, One factor at a time; PLM, Polarized light microscopy; PXRD, Powder X-ray diffraction; RH, Relative humidity; SDD, Spray-dried dispersion; SEM, Scanning electron microscopy; SMCC, Silicified microcrystalline cellulose; SSG, Sodium starch glycolate; ssNMR, Solid-state nuclear magnetic resonance; T g , Glass transition temperature; TOSS, Total spinning sideband suppression. AAPS PharmSciTech (2019) 20:331 DOI: 10.1208/s12249-019-1541-6 1530-9932/19/0000-0001/0 # 2019 American Association of Pharmaceutical Scientists