Mechanistic Models and Computer Software for Quality by Design In Formulation of Modified Release Dosage Forms

Modified release dosage forms (MRDFs) can be designed and manufactured in various shapes and structures using different materials. Depending on the design, formulation and properties of drug and excipients (e.g. polymers), drug release from MRDFs can undergo varying mechanisms. In addition, the external conditions such as mixing degree, pH and volume of the releasing medium, may play an important role in the release kinetics of the drug.  Therefore, thorough understanding of drug release mechanism of an MRDF and establishing a mechanistic model with consideration of such important factors are essential for quality by design (QbD) in the development of MRDFs with target performance. This presentation will review the difference between mechanistic modeling and statistical modeling and discuss how mechanistic modeling and computer software can be employed for QbD in formulation of MDRFs. Various multiparticulate systems will be analyzed as examples, which include matrix beads/pellets and minitablets with or without membrane coating, drug granules coated with polymer membrane, sugar pellets coated with drug layer and polymer coating. Prediction of in vivo performance from in vitro release profile and design of a MRDF from targeted in vivo plasma concentration profile will be demonstrated.