Implementation of Quality by Design (QbD) for development of bilayer tablets.

Bilayer tablets offer various drug release profiles for individual drugs incorporated in each layer of a bilayer tablet, which is rarely achievable by conventional tablets. These tablets also help avoid physicochemical incompatibilities between drugs and excipients. Successful manufacturing of such more complex dosage forms depends upon screening of material attributes of API and excipients as well as optimization of processing parameters of individual unit operations of the manufacturing process that must be strictly monitored and controlled to obtain an acceptable drug product quality and performance in order to achieve safety and efficacy per regulatory requirements. Optimizing formulation attributes and manufacturing processes during critical stages, such as blending, granulation, pre-compression, and main compression, can help avoid problems such as weight variation, segregation, and delamination of individual layers, which are frequently faced during the production of bilayer tablets. The main objective of this review is to establish the basis for the implementation of Quality by Design (QbD) system principles for the design and development of bilayer tablets, encompassing the preliminary and systematic risk assessment of critical material attributes (CMAs) and critical process parameters (CPPs) with respect to in-process and finished product critical quality attributes (CQAs). Moreover, the applicability of the QbD methodology based on its purpose is discussed and complemented with examples of bilayer tablet technology.

Multivariate curve resolution of overlapping voltammetric peaks: quantitative analysis of binary and quaternary metal mixtures.

The application of multivariate curve resolution-alternating least squares (MCR-ALS) to the quantitative analysis of different metal ion mixtures using voltammetric data is described. The performance of MCR-ALS was evaluated in the resolution and quantitation of overlapped voltammetric peaks obtained in the analysis of binary and quaternary mixtures of Cd(II), In(III), Pb(II) and Tl(I) metal ions by anodic stripping voltammetry. Quality assessment of qualitative and quantitative determinations was evaluated considering the effects of different constraints and of initial estimations. MCR-ALS results were validated and compared with those obtained by applying other well-established multivariate calibration methods, such as partial least squares (PLS) and direct classical least squares (DCLS) methods.