ABSTRACT
This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM.
Subject(s)
Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Polyurethanes/administration & dosage , Polyurethanes/chemistry , Administration, Oral , Chemistry, Pharmaceutical/methods , Dosage Forms , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Compounding/methods , Dyphylline/administration & dosage , Dyphylline/chemistry , Excipients/chemistry , Hot Temperature , Humans , Metoprolol/administration & dosage , Metoprolol/chemistry , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemistry , Porosity , Tablets/administration & dosage , Tablets/chemistryABSTRACT
Recent developments in material design have seen an exponential increase of polymers and polymer composites that can repair themselves in response to damage. In this review, a distinction is made between extrinsic materials, where the self-healing property is obtained by adding healing agents to the material to be repaired, and intrinsic materials, where self-healing is achieved by the material itself through its chemical nature. An overview of the crosslinking chemistries used in self-healing materials will be given, discussing the advantages and drawbacks of each system. The review is not only aiming to enable researchers to compare their ongoing research with the state-of-the-art but also to serve as a guide for the newcomers, which allows for a selection of the most promising self-healing chemistries.
