Abstract
A wide variety of formulations have been explored in attempt to improve the apparent aqueous solubility of poorly-water soluble drugs such as oil-in-water nanoemulsions (NE), oil-in-water microemulsions (ME) and drug nanoparticles (NPs). There would be advantage gained if two poorly-water soluble drugs could be combined in a single formulation, particularly with respect to the ability to personalise a patient’s medicine. In this study therefore, two novel combination formulations, which we have termed a “nanosusponanoemulsion (NSNE)” and a “nanosuspomicroemulsion (NSME)”, consisting of either NE or ME containing a low dose drug and NP comprised of a high dose drug, respectively have been studied. The particular aim of this study is to prove the principal that, by the rational design of NSNE and NSME, it is possible to prepare combination formulations suitable for the delivery of two poorly-water soluble drugs for use in personalised medicine.Studies involved the preparation and physico-chemical characterization of NSNE and NSME prepared from the mixing of NP, prepared by wet bead milling and stabilised by the anionic surfactant, sodium dodecyl sulphate (SDS), and either NE stabilised by the nonionic surfactant, Brij 97, and containing the triglyceride oil, glyceryl trioctanoate (TON) or a ME stabilised by SDS and containing either ethyl butyrate (EB) or ethyl caprylate (EC). Testosterone propionate (TP) was used as the low-dose model drug and was solubilised in the NE and ME, whilst griseofulvin (GF) was the high-dose model drug used to prepare the NPs. A range of physico-chemical techniques were used to characterize the individual systems, namely the NP, NE and ME, as well the NSNE and the NSME and included UV spectroscopy, photon correlation spectroscopy (PCS) as well as small angle neutron scattering (SANS) which was used to individually monitor the in situ stability of the individual components of the NSNE and NSME.
Significantly in the combined formulations, some of the GF from the NPs was solubilised in the NE and the ME. In addition, while the solubility of TP in the NE remained constant in the presence of the SDS-stabilised GF-NPs, the amount of TP in the ME decreased upon contact with the GF-NP, suggesting that the GF displaced some of the TP molecules in the ME. PCS studies showed that the particle size of GF-NP, when in the form of a NSNE, i.e. in contact with the NE initially increased in size but thereafter remained relatively stable whilst the particle size of GF-NP in the form of a NSME remained unchanged. On the other hand, the SANS studies indicated that the TP-containing NE with a low amount of TON were stable for at least 24 hours contact with the GF-NP when in the form of a NSNE. These results suggest that the NSNE is more suitable than the NSME for the administration of two poorly water-soluble drugs in a single formulation for use in personalised medicine.
| Date of Award | 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Margaret Lawrence (Supervisor) & Gino Martini (Supervisor) |