Supramolecular derivatives of selected bioactive compounds : a physicochemical study

The author’s objective was to prepare new solid phases of three bioactive compounds: the steroidal anticancer agent 2-methoxyestradiol [polymorphs and cyclodextrin (CD) inclusion complexes], its derivative 2-methoxyestradiol-bis-sulfamate (polymorphs), and the antiretroviral agent, nevirapine (co-crystals). The solubility and dissolution profiles of the three compounds and those of selected ‘supramolecularly-derived’ species were also assessed. Three distinct phases of 2-methoxyestradiol (2ME) were successfully isolated, the most stable form (a polymorph) by the recrystallisation method, an amorph by melt studies and a solvated form by recrystallisation. 2-methoxyestradiol-bis-sulfamate (2MES), in the form of a hemihydrate, remained unchanged when recrystallised from various solvents. Several CDs were used for possible 2-methoxyestradiol inclusion; these were α-, β -,γ-CD, and nine derivatised cyclodextrins. Co-precipitation and kneading techniques were employed in attempts to produce inclusion complexes. An inclusion complex of 2ME was isolated with each of the following: -CD, HPBCD, RAMEB, DIMEB and TRIMEB. Co-crystallisation of nevirapine was attempted using twelve potential co-formers with GRAS status. Two co-crystals, one with saccharin and one with rac-tartaric acid, were isolated by the co-precipitation method. Physicochemical characterisation techniques used to assess the thermal behaviour of the products included hot stage microscopy, differential scanning calorimetry and thermogravimetric analysis. UV spectrophotometry and elemental analysis were used for hostguest stoichiometric assay and purity determination respectively. X-ray powder diffraction and single crystal X-ray structure determination were used for structural analysis.

Grantor dc:publisher.institution

Department of Chemistry

Year dc:date.issued

2010

Author dc:creator

• Samsodien, Halima

Advisors dc:contributor.advisor

• Caira, Mino R
• Bourne, Susan

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/11427/6360

OAI identifier oai:identifier

oai:open.uct.ac.za:11427/6360