ABSTRACT
A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were spheronized using melted gelucire 50-13 as a binding material (BM). Experimentation was performed sequentially; a fractional factorial design was set up initially to screen the factors affecting the process, namely spray rate, quantity of BM, rotor speed, type of rotor disk, lubricant-glidant presence, additional spheronization time, powder feeding rate and quantity. From the eight factors assessed, three were further studied during process optimization (spray rate, quantity of BM and powder feeding rate), at different ratios of the solid mixture of CW and HPMC K100M. The study demonstrated that the novel hot melt process is fast, efficient, reproducible and predictable. Therefore, it can be adopted in a lean and agile manufacturing setting for the production of flexible pellet dosage forms with various release rates easily customized between immediate and modified delivery.
Subject(s)
Drug Implants/chemistry , Technology, Pharmaceutical/methods , Excipients/chemistry , Fats/chemistry , Hypromellose Derivatives/chemistry , Oils/chemistry , Polymethacrylic Acids/chemistry , Powders/chemistry , Research Design , Waxes/chemistryABSTRACT
It is well established that several diseases exhibit circadian behavior, following the relevant rhythm of the physiological functions of the human body. Their study falls in the fields of chronobiology and chronotherapeutics, the latter being essentially the effort of timely matching the treatment with the disease expression, in order to maximize the therapeutic benefits and minimize side effects. Pulsatile drug delivery is one of the pillars of chronopharmaceutics, achieved through dosage form design that allows programmable release of active pharmaceutical ingredients (APIs) to follow the disease's time profile. Its major characteristic is the presence of lag phases, followed by drug release in a variety of rates, immediate, repeated or controlled. The scope of this review is to summarize the recent literature on pulsatile oral drug delivery systems and provide an overview of the ready to use solutions and early stage technologies, focusing on the awarded and pending patents in this technical field during the last few years.
Subject(s)
Drug Chronotherapy , Drug Delivery Systems , Pharmaceutical Preparations/administration & dosage , Administration, Oral , Chronobiology Phenomena , Humans , Patents as Topic , Pulse Therapy, DrugABSTRACT
Pellets exhibit major therapeutic and technical advantages which have established them as an exceptionally useful dosage form. A plethora of processes and materials is available for the production of pellets, which practically allows inexhaustible configurations contributing to the flexibility and versatility of pellets as drug delivery systems. The scope of this review is to summarize the recent literature on pelletization processes for pharmaceutical applications, focusing on the awarded and pending patents in this technical field. The first part of the article provides an overview of innovation in pelletization processes, while the second part evaluates their novel applications.
