QbD Assisted Development of a Compartment and Sequential Drug Delivery System for Periodontotherapy

Abstract

Periodontitis, the burgeoning disease, is at an alarming stage. Although this has triggered dedicated research in this area, as the disease itself demands a multi-component therapy, there is an unmet need for a compartment and sequential drug delivery system to ameliorate disease symptoms completely. The hypothesized work consists of multitherapeutic agents such as an antibiotic, a COX-II inhibitor, an MMP inhibitor, and a bone regenerating agent in an in-situ gel. However, for the development of the system, as mentioned above, a thorough investigation at each stage is necessary; therefore, the quality-by-design approach was adopted. Furthermore, the current work is a pursuit of studying the quality by design aspects for the fabrication of a compartment system, i.e., in-situ gel for periodontal delivery. The proposed system in-situ gel consists of antibiotic and nano-encapsulating microcapsules. Furthermore, the microcapsules contain a COX-II inhibitor and nanoparticles of MMP inhibitor and bone regenerating agent for complete amelioration of periodontitis. To develop the system as per the QbD approach, the first initial trials and runs were conducted, which helped to decide the quality target product profile (QTPP). However, based on QTPP, critical quality attributes (CQA), critical process parameters (CPP), and critical material attributes (CMAs) were decided for each stage product, i.e., in-situ gel, microcapsules, and nanoparticles. To assess the influence of CPPs and CMAs on CQAs, Pareto charts were constructed, and various risks, along with possible failure modes were studied. In conclusion, the above work will serve as a well-designed scientific mouthpiece for developing a compartment system for periodontotherapy.

Keywords: Quality by design; critical material attributes; critical process parameters; critical quality attributes; periodontotherapy.; quality target product profile; risk assessment.