title: Rapid exploration of curing process design space for production of controlled-release pellets.
abstract: Time and cost are among the most often cited hurdles limiting the rate and extent of adoption of Quality by Design (QbD) and Process Analytical Technology. In this article, we demonstrate that, with appropriate techniques, a key QbD element can be achieved with amount of resources comparable to classical development approach. To control the dissolution rate of a highly soluble drug substance from latex polymer coated pellets, we have examined the effect of key variables affecting the curing process step by an experimental design study. To explore and characterize the Design Space, we have produced and tested 62 distinct pellet samples. To achieve this in a reasonable amount of time, we have developed a scaled-down automated dissolution method that demonstrated excellent correlation to the classical method. By careful planning of experimentation, we were able to obtain all samples from just two batches of pellet cores. The curing process Design Space was explored by statistical modeling of samples obtained from the first batch. Robustness and repeatability of the Design Space at the edge of failure was preliminarily investigated by analysis of selected samples from the second batch with encouraging results.
authors: Lek Pharmaceuticals, d.d., Sandoz Development Center Slovenia, Verovškova 57, Ljubljana SI-1526, Slovenia.
authors: Katja
authors: K
authors: Kristan
authors: Matej
authors: M
authors: Horvat
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D015195:Drug Design; D007840:Latex / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011786:Quality Control; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D007840:Latex; D011108:Polymers