ABSTRACT
The application of three-dimensional printing (3DP) in the pharmaceutical industry brings a broad spectrum of benefits to patients by addressing individual needs and improve treatment success. This study investigates the sustained release properties of 3DP tablets containing Theophylline (TPH), which is commonly used to treat respiratory diseases and recently having a comeback due to its potential in the treatment of conditions like Covid-19. Since TPH is a narrow therapeutic window (NTW) drug with serious side effects in the event of overdose, the release properties must be observed particularly closely. We employed a state-of-the-art single screw extrusion 3D printer, which is fed with granules containing the drug. By employing a Taguchi orthogonal array design of experiments (DOE), tablet design parameters and factor related process stability were sought to be evaluated fundamentally. Following this, examinations regarding tailored TPH dosages were undertaken and a relationship between the real printed dose of selected tablet designs and their sustained drug release was established. The release profiles were analyzed using different mathematical model fits and compared in terms of mean dissolution times (MDT). Finally, in-vivo/in-vitro correlation (IVIVC) and physiologically based pharmacokinetic (PBPK) modeling showed that a paradigm patient group could be covered with the dosage forms produced.
Subject(s)
Delayed-Action Preparations , Drug Liberation , Printing, Three-Dimensional , Tablets , Theophylline , Theophylline/chemistry , Theophylline/administration & dosage , Theophylline/pharmacokinetics , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Humans , Drug Compounding/methods , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/pharmacokinetics , Bronchodilator Agents/chemistryABSTRACT
This study, using functional magnetic resonance imaging (fMRI) technology, demonstrated that distant intentionality (DI), defined as sending thoughts at a distance, is correlated with an activation of certain brain functions in the recipients. Eleven healers who espoused some form for connecting or healing at a distance were recruited from the island of Hawaii. Each healer selected a person with whom they felt a special connection as a recipient for DI. The recipient was placed in the MRI scanner and isolated from all forms of sensory contact from the healer. The healers sent forms of DI that related to their own healing practices at random 2-minute intervals that were unknown to the recipient. Significant differences between experimental (send) and control (no send) procedures were found (p = 0.000127). Areas activated during the experimental procedures included the anterior and middle cingulate area, precuneus, and frontal area. It was concluded that instructions to a healer to make an intentional connection with a sensory isolated person can be correlated to changes in brain function of that individual.