Prednisolone crystalline forms

PW Taylor Jr, DE Wurster. Dissolution kinetics of certain crystalline forms of prednisolone II Influence of low concentrations of sodium lauryl sulfate. J Pharm Sci 54 1654-1658, 1965. 

For this reason, the amorphous form is often preferred over the crystalline form and several drugs, including hydrocortisone and prednisolone, are marketed in the amorphic form. 

Variations in lattice energies between amorphous and crystalline forms can significantly influence a drug s aqueous solubility, and increases of several hundredfold were observed for morphine and benzimidazole derivatives. Furthermore, a substance may exist in more than one crystalline form, such as chloramphenicol, dehydroepiandrosterone (DHEA), progesterone, sul-fathiazole, carbamazepine, cortisone, or prednisolone, to name a few. Polymorphic transformations, routinely observed for pharmaceuticals, are structural differences resulting from different crystal arrangements of molecules in the solid state. Although thermodynamic differences between polymorphs disappear once dissolved. 

In another study by Byrn et al., five crystalline forms of prednisolone tert-butylacetate were studied and correlations to crystal structures and oxygen reactivity were made. Four of the forms were solvatomorphic. 

Crystalline packing is an important parameter for auto-oxidation in the sohd state, as molecular oxygen must be able to access susceptible moieties in the molecule. Lyn et al. [63] showed that only one (hexagonal form) of the five different polymorphic forms of prednisolone tert-butylacetate were susceptible to oxidation, yielding the 11-ketone product. The authors attributed this oxidative reactivity to channels in the crystal structure allowing access to the labile 11-alcohol position. Bryn et al. [64] also identified a similar phenomenon in the photo-mediated oxidation of 21-cortisol tert-butylacetate to the corresponding ketone. 

Solid-state NMR is extremely useful in investigating solid modifications of both the drug substance and the solid drug product. Crystalline material typically affords sharp and narrow C resonance peaks similar to solution spectra. In addition, because the molecules in one polymorphic form of a drag are arrayed differently than those in another polymorphic form, differences in the solid-state spectra of the polymorphs are quite apparent. For example. Fig. 7.13 clearly shows that there are a number of differences in the solid-state C CP/ MAS spectra of the two prednisolone polymorphs [56]. 

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