Effect of Vehicle Composition on the Preparation of Different Types of Dapsone Crystals for Topical Drug Delivery

Topical formulations composed of
API-pure crystals have been increasingly
studied, especially in regards to the impact of particle size in penetration
efficiency. Less attention, however, has been devoted to the solid-state
properties of drugs delivered to the skin. In this study, we address
the effect of formulation composition on the crystal form existing
in topical products. Dapsone (DAP) gel formulations were prepared
by mixing an organic solution containing DAP with an aqueous solution
containing polymers and preservatives. The organic solvent was chosen
as ethoxydiglycol (DEGEE), polyethylene glycol (PEG), or 1-methyl-2-pirrolidone
(MPR) to assess the impact of composition on DAP crystal form. Such
solvent variations resulted in different particulate matter. In terms
of crystalline nature, the presence of DEGEE in formulations induced
the crystallization of DAP hydrate, while PEG cocrystal and a mixture
of hydrate and MPR solvate crystallized from the same amounts of PEG
and MPR, respectively. Microscopic analysis of the gels showed heterogeneous
particles with different characteristics. The behavior of gels after
application to the skin was also tested. Interestingly, the different
formulations seemed to accumulate in different regions of the skin.
This could be the result of the effect of vehicle composition/excipients
on the characteristics of the skin, such as hydration. The site-specific
accumulation, however, was more pronounced in crystal-loaded gels
as opposed to blank formulations. These results indicate that future
studies should consider the effect of formulation composition on the
API crystal form landscape as part of the strategies used to successfully
target drug delivery to the skin.