title: Systematic identification of thermal degradation products of HPMCP during hot melt extrusion process.
abstract: A systematic identification of the degradation products of hydroxypropyl methylcellulose phthalate (HPMCP) during hot melt extrusion (HME) has been performed. A reverse phase HPLC method was developed for the extrudates of both hydroxypropyl methylcellulose acetate succinate (HPMCAS) and HPMCP polymers to quantify their thermal hydrolytic products: acetic acid (AA), succinic acid (SA) for HPMCAS and phthalic acid (PA) for HPMCP, without hydrolysing the polymers in strong alkaline solutions. The polymers were extruded in the temperature range of 160-190 °C at different screw rotation speeds and hydrolytic impurities were analysed. Investigation of extruded HPMCP showed an additional thermal degradation product, who is structural elucidation revealed to be phthalic anhydride (PAH). Moreover, two environmental analytical impurities, dimethyl phthalate and methyl benzoate formed in situ were recorded on GC-MS and their origin was found to be associated with PAH derivatization. Using the experimental data gathered during this study, a degradation mechanism for HPMCP is proposed.
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom.
authors.forename: Hrushikesh
authors.initials: H
authors.lastname: Karandikar
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom.
authors.forename: Rohan
authors.initials: R
authors.lastname: Ambardekar
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kelly
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom.
authors.forename: Tim
authors.initials: T
authors.lastname: Gough
authors.affiliation: Centre for Pharmaceutical Engineering Science, University of Bradford, Richmond Road, Bradford, Yorkshire BD7 1DP, United Kingdom. Electronic address: a.paradkar1@bradford.ac.uk.
authors.forename: Anant
authors.initials: A
authors.lastname: Paradkar
mesh_terms: D019342:Acetic Acid / Q000032:analysis; D001565:Benzoates / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D008401:Gas Chromatography-Mass Spectrometry; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D010795:Phthalic Acids / Q000032:analysis; D010796:Phthalic Anhydrides / Q000032:analysis; D013055:Spectrophotometry, Infrared; D019802:Succinic Acid / Q000032:analysis; D013818:Thermogravimetry
chemical_list: D001565:Benzoates; D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C024629:dimethyl phthalate; C044605:methyl benzoate; C032279:phthalic acid; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D019802:Succinic Acid; D019342:Acetic Acid; C043103:phthalic anhydride
keywords: Degradation products and mechanism; HME; HPMCAS; HPMCP; Thermal degradation