Corticosteroids hydrocortisone sodium phosphate

Dexamethasone, prednisolone and hydrocortisone are systemically active via the rectal route. The best chemical form of the active substance must be chosen and a dosage form that provides good release of the active substance. A corticosteroid as salt in solution is often optimal for an enema and the preparation is easy. As a solution in water it avoids problems such as release from a fatty base and subsequent dissolution. Dexamethasone and prednisolone for instance are used as sodium phosphate salts. Conversion and factorisation must not be forgotten. For stability reasons... 

Esters of corticosteroids with a polyvalent acid group, for example succinic acid or phosphoric acid, are soluble in their salt form. This is because most of the non-esterified acid groups are deprotonated when sufficiently high pH is chosen. Examples of corticosteroids which are esterified with polybasic acids are hydrocortisone sodium succinate, prednisolone sodium phosphate and dexamethasone sodium phosphate. In an aqueous medium with a pH of about 7 or higher, hydrocortisone sodium succinate is largely ionised and thus fairly soluble. At this pH, however, the hydrolysis of the ester is quite fast (this ester is most stable at a pH of about 4.5). As a result, dissolved in water, this substance is unstable and therefore its shelf life is limited. 

In aqueous solution, prednisolone sodium phosphate and dexamethasone sodium phosphate are more stable than hydrocortisone sodium succinate. At a pH of about 8, the acid groups are sufficiently ionised to make the substance very soluble, while the phosphate ester is reasonably stable at this pH. Water soluble corticosteroids are mainly used in parenteral preparations, eye drops, oral mixtures and enemas. Examples are prednisolone oral mixtures and dexamethasone injections. 

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