Effect of modulation of alimentary and formulation pH on the pharmacokinetics of BCS-Class I, II, III, and IV compounds in rats following cassette dosing.

OBJECTIVE

This study was performed to appraise the effect of modulation of formulation pH and abdominal pH on the pharmacokinetics (PK) of the selected compounds from different drugs of the Biopharmaceutics Classification System (BCS) when administered via cassette dosing in rats.

METHODS

Pharmacokinetics of four different BCS class drugs viz. propranolol HCl, diclofenac sodium, atenolol, and acetazolamide (BCS-I, II, III, and IV, respectively) in different formulation pH conditions and different abdominal pH conditions were evaluated. The animal groups were dosed orally.

RESULTS

Propranolol HCl exhibited a significant increase in area under the curve (AUC0-last) when the alimentary canal pH was modulated to acidic (195%), and a significant increase in maximum concentration at a given time point (Cmax) (102%) for formulation with basic pH in healthy animals. Diclofenac exhibited a significant increase in AUC0-last when the alimentary canal pH was modulated to acidic (95%), and a significant decrease in Cmax (55%) for formulation with basic pH in healthy animals. Atenolol displayed a substantial increase in AUC0-last in basic pH conditions in the alimentary canal (38%), and a significant decrease in AUC0-last (49%) for basic pH formulation in healthy animals. Acetazolamide demonstrated a considerable increase in AUC0-last when alimentary canal pH was modulated to basic (55%), and a substantial enhancement in AUC0-last (39%) for acidic pH formulation in healthy animals.

CONCLUSION

The results suggest that both alimentary canal conditions with acidic and basic pH and formulation with acidic and basic pH have a considerable influence on the PKs of different compounds not only based on their acid dissociation constant (pKa) but also independently on the pH in the area of absorption in the alimentary canal and salt form of the compound.