Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.
Pharm Res
; 34(12): 2689-2697, 2017 Dec.
Article
in En
| MEDLINE
| ID: mdl-28929263
ABSTRACT
PURPOSE:
Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated.METHODS:
Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC.RESULTS:
Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO.CONCLUSIONS:
Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polyethylene Glycols
/
Anti-Inflammatory Agents, Non-Steroidal
/
Indomethacin
/
Cimetidine
/
Drug Compounding
/
Excipients
/
Histamine H2 Antagonists
Language:
En
Journal:
Pharm Res
Year:
2017
Document type:
Article
Affiliation country: