Ali, Shazia; (2001) Adsorption of the poloxamer surfactants onto model hydrophobic surfaces in suspension systems. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The work presented in this thesis is concerned with adsorption of the poloxamer surfactants to model hydrophobic drug surfaces for the purpose of stabilising pharmaceutical suspensions. A poloxamer molecule consists of a central poly(propylene oxide) (PPO) chain and two terminal poly(ethylene oxide) (PEO) chains. The length of the chains can be varied to obtain a wide range of molecular weights and PEO/PPO ratios which can alter their adsorption characteristics and stabilising capabilities. The first type of adsorption studies were performed in an attempt to quantify the extent of adsorption of the poloxamers to hydrophobic drug surfaces (ibuprofen and ketoprofen). It was found that all the investigated surfactants showed a higher affinity to ibuprofen than ketoprofen. The ranking obtained for extent of adsorption was as follows: P407>P 188>P237>P338. Studies were then conducted using the theories of interfacial phenomena in order to characterise the drug surfaces. Ibuprofen was found to possess a more hydrophobic surface and thus it was concluded that the poloxamers show a greater affinity for very hydrophobic surfaces. The second adsorption study used the technique isothermal titration microcalorimetry to look at the thermodynamics of the adsorption process. The results obtained supported the findings from the previous adsorption studies where exactly the same ranking for adsorption was obtained. Furthermore, this study also showed that the poloxamers demonstrated a higher affinity for the ibuprofen surface. The final study consisted of determining the ability of the poloxamers to stabilise the drug suspensions. By assessing the particle size over a period of six months it was found that, in keeping with adsorption studies, P407 produced the most stable suspensions on both drug surfaces. Thus it can be concluded that in order for a poloxamer surfactant to adsorb strongly to a surface and form stable pharmaceutical suspensions, the molecule must consist of a high molecular weight as well as an equally balanced PEO/PPO ratio such as P407. An ideal adsorbing surface should be very hydrophobic, however if the surface is relatively hydrophilic, then a poloxamer which fits the above criteria can still effectively stabilise the suspension.

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