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

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.

Analytical and Computational Methods for the Determination of Drug-Polymer Solubility and Miscibility

“…Hanada et al demonstrated atomic level drug-polymer interaction in ASD of Posaconazole and HPMC using 19 F solid-state NMR . Apart from this, there are multiple reports of drug-polymer miscibility using solid-state NMR. ,− …”

Development and Validation of Reverse‐Phase High‐Performance Liquid Chromatography Method for Estimation of Itraconazole through Hydroxypropyl Methylcellulose Acetate Succinate based Polymeric Films using Quality by Design principles

“…It is poorly water‐soluble and classified as BCS class II [3]. The drug is often used as a model drug for preparing amorphous solid dispersions either by spray drying or hot melt extrusion method for solubility enhancement [4–6]. Being a water‐insoluble molecule, there are also obvious challenges in developing a robust analytical method for the estimation of itraconazole from the formulation.…”