Biowaiver monograph for immediate-release solid oral dosage forms: Amlodipine besylate.

Amlodipine besylate is a calcium channel blocker widely used for treating hypertension and coronary artery disease. This biowaiver monograph evaluates the suitability of BCS-based biowaivers for immediate-release (IR) oral dosage forms containing amlodipine besylate. A comprehensive review of available data was conducted to assess solubility, permeability, bioavailability, dissolution, pharmacokinetics, safety, and excipient interactions. Amlodipine besylate is a highly soluble base across the pH range 1.2-6.8. Although mass balance in humans showed a fraction absorbed of ≥96%, inconclusive in vitro permeability data revealed a risk associated with a BCS class I classification. Nonetheless, several IR formulations, including fixed-dose combinations (FDC), have demonstrated bioequivalence (BE). This has been related to very rapid in vitro dissolution profiles at 75 rpm for the reference product, as recommended by guidelines. Taken together, the risk of BE failure due to formulation or manufacturing differences is low, provided a very rapid dissolution and the use of standard excipients. With a favorable safety profile and a wide therapeutic index, the overall evidence leads to a conservative classification of amlodipine besylate to BCS III. Thus, IR products containing this drug can be candidates for the BCS-based biowaiver, thereby enabling substitution of surrogate in vitro methods for in vivo BE approval of multisource products.