Quality by design approach for optimizing the formulation and physical properties of extemporaneously prepared orodispersible films

Abstract

The quality by design (QbD) approach was applied for optimizing the formulation of extemporaneously prepared orodispersible films (ODFs) using Design-Expert® Software. The starting formulation was based on earlier experiments and contained the film forming agents hypromellose and carbomer 974P and the plasticizer glycerol (Visser et al., 2015). Trometamol and disodium EDTA were added to stabilize the solution. To optimize this formulation a quality target product profile was established in which critical quality attributes (CQAs) such as mechanical properties and disintegration time were defined and quantified. As critical process parameters (CPP) that were evaluated for their effect on the CQAs the percentage of hypromellose and the percentage of glycerol as well as the drying time were chosen. Response surface methodology (RMS) was used to evaluate the effects of the CPPs on the CQAs of the final product. The main factor affecting tensile strength and Young's modulus was the percentage of glycerol. Elongation at break was mainly influenced by the drying temperature. Disintegration time was found to be sensitive to the percentage of hypromellose. From the results a design space could be created. As long as the formulation and process variables remain within this design space, a product is obtained with desired characteristics and that meets all set quality requirements.

Keywords: Critical quality attributes; Extemporaneous pharmacy preparations; Glycerol (PubChem CID: 753); Hypromellose (PubChem CID: 57503849); Optimizing formulation; Orodispersible films; Quality by design; Quality target product profile.