Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.
Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility.
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
G
G
Verstraete
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
J
J
Van Renterghem
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
P J
PJ
Van Bockstal
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
S
S
Kasmi
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
B G
BG
De Geest
Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Ghent, Belgium.
T
T
De Beer
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
J P
JP
Remon
Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
C
C
Vervaet
D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation; D004400:Dyphylline / Q000008:administration & dosage* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D011140:Polyurethanes / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011140:Polyurethanes; D013607:Tablets; D004400:Dyphylline; D000082:Acetaminophen; D013806:Theophylline
High drug load; Hot melt extrusion; Injection molding; Rheology; Sustained release; Thermoplastic polyurethanes