Implantable drug delivery systems (IDDSs) offer good patient compliance and allow the controlled delivery of drugs over prolonged times. However, their application is limited due to the scarce material selection and the limited technological possibilities to achieve extended drug release. Porous structures are an alternative strategy that can overcome these shortcomings. The present work focuses on the development of porous IDDS based on hydrophilic (HPL) and hydrophobic (HPB) polyurethanes and chemical pore formers (PFs) manufactured by hot-melt extrusion. Different PF types and concentrations were investigated to gain a sound understanding in terms of extrudate density, porosity, compressive behavior, pore morphology and liquid uptake. Based on the rheological analyses, a stable extrusion process guaranteed porosities of up to 40% using NaHCO3 as PF. The average pore diameter was between 140 and 600 µm and was indirectly proportional to the concentration of PF. The liquid uptake of HPB was determined by the open pores, while for HPL both open and closed pores influenced the uptake. In summary, through the rational selection of the polymer type, the PF type and concentration, porous carrier systems can be produced continuously via extrusion, whose properties can be adapted to the respective application site.
In product development, it is crucial to choose the appropriate drug manufacturing route accurately and timely and to ensure that the technique selected is suitable for achieving the desired product quality. Guided by the QbD principles, the pharmaceutical industry is currently transitioning from batch to continuous manufacturing. In this context, process understanding and prediction are becoming even more important. With regard to hot melt extrusion, the process setup, optimization and scale-up in early stages of product development are particularly challenging due to poor process understanding, complex product-process relationship and a small amount of premix available for extensive experimental studies. Hence, automated, quick and reliable process setup and scale-up requires simulation tools that are accurate enough to capture the process and determine the product-process relationships. To this end, the effect of process settings on the degradation of the active pharmaceutical ingredient (API) in a lab-scale Leistritz ZSE12 extruder was investigated. As part of the presented study, the limitations of traditional process analysis using integral process values were investigated, together with the potential that simulations may have in predicting the process performance and the product quality. The results of our investigation indicate that the average melt temperatures and the exposure times in specific zones along the screw configuration correlate well with the API degradation values and can be used as potent process design criteria to simplify the process development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.