When it is too much: Identifying butamben excess on the surface of pharmaceutical preformulation samples by Raman mapping

Abstract

In nanostructured lipid carriers (NLC), the type and amount of excipients will determine API solubility and therefore the maximum drug load. Butamben is a topical local anesthetic which formulation in lipid-based DDS is difficult due to its affinity for hydrophilic solvents, which might not miscible with the solid lipid. This indicates that a medium polarity excipient might be needed. The first step of this study comprised a throughout screening study to evaluate API solubilization in different excipients. Then excipients with low (Dhaykol® 6040 LW) and high (Capryol® 90) solubilization capacities were selected for microscopic evaluation by Raman mapping. For Capryol® 90 a mixture design of experiments was carried out to study the proportions of excipients, using as responses the DHI (distributional homogeneity index) and standard deviation of the histograms. Clusters of the API were observed I the samples prepared with Dhaykol®, confirming the low solubilization capacity. In this case, DHI was an adequate parameter to indicate solubilization/miscibility. In the case of Capryol®90 samples, no clusters were observed due to its higher solubilization capacity, however since it was homogeneously distributed throughout the analyzed surface, the DHI values were low, indicating the need for a 3D image.

Neither too little nor too much: finding the ideal proportion of excipients

“…More recently, our research group showed that 3D images might be required for visualizing drug overload when surface analysis is not sufficient. 6 In particular, Raman confocal microscopy enables 3D images acquisition that can be crucial in some situations, including pharmacological, biological and pharmaceutical studies. For instance, Gotter et al 17 applied this approach to follow the dithranol (antipsoriasis) diffusion in artificial acceptor membranes using semisolid formulations, while Chen et al 18 tracked the fate of the anticancer drug cisplatin in cells, proving the great potential of this technique for theragnostic purposes.…”

“…even though it is poorly water soluble, it also presents poor solubility in lipids. 6 Homogeneity can be evaluated either in a macroscopic way, by visual inspection and using microscopic imaging, especially chemical imaging methods that allow evaluating the chemical distribution. [7][8][9] .…”

Neither too little nor too much: finding the ideal proportion of excipients

“…even though it is poorly water soluble, it also presents poor solubility in lipids. 6 Homogeneity can be evaluated either in a macroscopic way, by visual inspection and using microscopic imaging, especially chemical imaging methods that allow evaluating the chemical distribution. [7][8][9] .…”

“…More recently, our research group showed that 3D images might be required for visualizing drug overload when surface analysis is not sufficient. 6 In particular, Raman confocal microscopy enables 3D images acquisition that can be crucial in some situations, including pharmacological, biological and pharmaceutical studies. For instance, Gotter et al 17 applied this approach to follow the dithranol (antipsoriasis) diffusion in artificial acceptor membranes using semisolid formulations, while Chen et al 18 tracked the fate of the anticancer drug cisplatin in cells, proving the great potential of this technique for theragnostic purposes.…”