title: Investigation and correlation of physical stability, dissolution behaviour and interaction parameter of amorphous solid dispersions of telmisartan: a drug development perspective.
abstract: The aim of this study was to investigate if amorphous solid dispersions of telmisartan, prepared in presence of different polymers, exhibit different structural and thermodynamic characteristics and whether these differences can be correlated to their physical stability (time to crystallisation) and dissolution behaviour. Amorphous samples were prepared by melt quenching. The resulting amorphous materials were characterised using X-ray diffraction, Raman spectroscopy and differential scanning calorimetry. All freshly prepared samples were completely X-ray amorphous (with a halo being the only feature in the diffractograms). The shape of the halos in the diffractograms varied suggesting structural variations in the near order of the molecules between the different amorphous solid dispersions (ASDs). Principal component analysis of the Raman spectra of the various ASD revealed that the samples clustered in the scores plot, again suggesting structural differences due to the presence of different drug-polymer interaction. The ranking of the samples with respect to physical stability and interaction parameter was: ASD of telmisartan:eudragit>ASD of telmisartan:soluplus>ASD of telmisartan:HPMC>ASD of telmisartan:PVP>amorphous telmisartan. The interaction parameter, calculated by using the Flory Huggins theory, showed a good correlation with the experimentally determined stability whereas a weak correlation was found with dissolution behaviour of different ASD. This study showed that correlation of physical stability and dissolution behaviour with calculated interaction parameter is possible for the same amorphous systems prepared by using different polymers. This could aid in selecting the most appropriate polymer for the development of optimised formulations containing amorphous drugs. It can be concluded that ASD prepared by using different polymers have different structural and thermal properties. These differences affect the physical stability and dissolution profiles of the amorphous solids. Thus, choosing the right polymer for preparing ASD is critical for producing materials with desired dissolution profiles and enhanced stability.
authors.affiliation: Department of Drug Discovery Support, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss 88397, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Dukeck
authors.forename: P
authors.initials: P
authors.lastname: Sieger
authors.forename: P
authors.initials: P
authors.lastname: Karmwar
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004355:Drug Stability; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D000077333:Telmisartan
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D011109:Polymethacrylic Acids; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D008747:Methylcellulose; D011205:Povidone; D000077333:Telmisartan
keywords: Amorphous; Dissolution; Drug–polymer interaction; Solid dispersions; Stability; Telmisartan