New drug entities frequently suffer from low solubility and present significant formulation challenges. One of the leading technologies utilized to overcome the low solubility of drugs is the formation of amorphous solid dispersions via spray drying of the API with an excipient. While a number of excipients have been utilized to create amorphous solid dispersions, hypromellose acetate succinate (HPMCAS) has proven to be highly effective and versatile in creating dispersions that demonstrate enhanced free drug levels in solution and inhibit recrystallization. To date, there are no excipients that have been specifically developed for spray drying applications and the excipients used in this application space were all developed for other applications such as enteric coatings and are not optimized for the spray drying process.
The present study compares AFFINISOL™ High Productivity HPMCAS, a new grade of HPMCAS designed specifically for spray drying, to standard HPMCAS. The High Productivity HPMCAS has reduced viscosity compared to standard commercial HPMCAS, allowing for increased throughput and reduced use of organic solvent in the spray drying process. Spray drying performance of the two HPMCAS materials was compared by measuring solution mass flow rate as a function of applied pressure during nozzle atomization testing. A head pressure was applied to the solution container and the resulting mass flow through the nozzle was measured using a Micromotion Coriolis mass flow meter. The size of the spray dried particles were measured using a Malvern Mastersizer 2000 Scirocco particle size analyzer with a variable dispersive air pressure. It was found that to match the atomization performance of standard HPMCAS, the concentration of High Productivity HPMCAS in solution had to be increased by 1.7x relative to standard HPMCAS. In addition, viscosity vs. shear rate at constant temperature of the HP HMPCAS was measured and compared to that of standard HPMCAS. Furthermore, solutions at low concentration show a Newtonian viscosity behavior as a function of the shear rate, without any onset of pseudoplasticity in the detectable shear rate region. With an increase in concentration a small onset of pseudoplasticity becomes apparent and is more pronounced for the conventional HPMCAS than for the High Productivity HPMCAS. Finally, this study will discuss the in vitro drug release rate and crystallization inhibition of amorphous spray dried dispersions formed with itraconazole and phenytoin.
See more of this Group/Topical: Pharmaceutical Discovery, Development and Manufacturing Forum