Reducing mechanical activation-induced amorphisation of salbutamol sulphate by co-processing with selected carboxylic acids
File Type:
Microsoft WordItem Type:
Journal ArticleDate:
2013Access:
openAccessCitation:
Curtin V, Amharar Y, Gallagher KH, Corcoran S, Tajber L, Corrigan OI, Healy AM, Reducing mechanical activation-induced amorphisation of salbutamol sulphate by co-processing with selected carboxylic acids, International Journal of Pharmaceutics, 456, 2, 2013, 508 - 516Download Item:
Curtin paper 2_TARA.doc (Microsoft Word) 185Kb
VCurtin_paper 2_figures.docx (Unknown) 811.8Kb
Abstract:
The unintentional generation of amorphous character in crystalline active pharmaceutical ingredients (APIs) is an adverse consequence of mechanical activation during dosage form manufacture. In this study, we assess and compare the ability of low glass transition temperature (Tg) dicarboxylic acids to mitigate amorphisation of a model API, salbutamol sulphate (SS), on both co-milling and co-mixing. SS processed alone, as well as co-milled and co-mixed composites of the API with glutaric acid (GA), adipic acid (AA) and pimelic acid (PA) were characterised by powder X-ray diffraction (pXRD), differential scanning calorimetry (DSC) and dynamic vapour sorption (DVS). Milling and dry mixing of SS both resulted in pXRD amorphous materials. No amorphous content of SS was detected by DVS on co-milling with 50% (w/w) GA, while amorphisation was more than halved, relative to the API milled alone, on co-milling with 50% (w/w) AA and PA, respectively. Co-mixing with each excipient also resulted in a decrease in API amorphicity, although the extent of reduction was considerably less compared to the co-milling experiments. The solubility (Solexcipient) of each excipient in amorphous SS was determined by thermal methods. No further reduction in API amorphisation was achieved on co-mixing with 50% (w/w) excipient, compared to concentrations corresponding to the solubility of each excipient in the amorphous API (SolGA=36%, SolAA=21%, SolPA=22%). PXRD confirmed gradual dissolution over time of GA in amorphous SS on co-mixing. In contrast to co-mixing, co-milling SS at excipient weight fractions above their respective solubilities in the amorphous drug resulted in further reductions in API amorphisation. This is thought to be due to the generation of a molecular dispersion of amorphous API, supersaturated with excipient, thereby leading to a more pronounced composite Tg lowering effect. The results indicate that co-processing with low Tg excipients is an effective strategy at minimising amorphisation of an API on mechanical activation.
Author's Homepage:
http://people.tcd.ie/ltajberhttp://people.tcd.ie/healyam
Description:
PUBLISHED
Author: TAJBER, LIDIA; HEALY, ANNE
Type of material:
Journal ArticleSeries/Report no:
International Journal of Pharmaceutics456
2
Availability:
Full text availableKeywords:
Salbutamol sulphate, Mechanical activation, Glass transition temperature, Crystalline, AmorphousDOI:
http://dx.doi.org/10.1016/j.ijpharm.2013.08.025ISSN:
0378-5173Licences: