(607b) 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.