QbD based approach for formulation development of spray dried microparticles of erlotinib hydrochloride for sustained release

Abstract In the present study Quality by design (QbD) principles were applied in formulating microparticles of erlotinib HCl (ERL), a lipophilic anticancer drug by spray drying. The study was done such that the QbD approach would demonstrate efficient feasibility in formulating the product and achieving the desired sustained release profile from the microparticles. After defining the quality target product profile (QTPP), the use of risk assessment by Ishikawa diagram assisted in identification of three risk factors namely the concentrations of polycaprolactone (PCL) and polyvinyl alcohol (PVA), and inlet temperature of spray dryer. A Box-Behnken design was used to study the effect of these three screened factors on particle size and drug encapsulation efficiency and sustained release duration. The multivariate DoE was able to show the impact of critical process parameters and critical material attributes on critical quality attributes (CQAs) and came out with a suitable design space which would yield the desired quality responses. The optimized formulation by the QbD approach gave promising IC50 values against the lung cancer cells (A549) indicating improved therapeutic efficacy and effective sustained release potential of the formulated microparticles.