Formulation stage bioequivalence

Zemplar (paricalcitol) injection is a synthetically manufactured selective vitamin D receptor activator (SVDRA) indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease (CKD) stage 5. The U.S. Food Drug Administration (FDA) approved a capsule form of Zemplar for development to satisfy a need for an oral formulation. The objective of study M04-693 was to assess the bioequivalencies of several dosage strengths of paricalcitol capsules under fasting conditions. 

In case of partial change in the formulations during the development stage, clinical data with the current formulation can be used for the application data if bioequivalence between both formulations is confirmed. In cases of a slight change in oral formulation such cis a vehicle before Phase II trials, the dissolution test can be acceptable instead of the bioequivalence study. 

Figure 2.5 Stages in drug absorption from an extravascular administration site (stomach, small intestine, intramuscular injection). Only drug in solution is absorbed. If the rate of dissolution (K2) is less than the rate of absorption (K3) then the rate at which drug is released from the dosage form controls absorption. This permits modified or sustained-release formulations, but can also lead to bioequivalence problems.

---