ABSTRACT
Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.
Subject(s)
Chemistry, Pharmaceutical/methods , Pharmacokinetics , Animals , Biological Availability , Chemistry, Pharmaceutical/instrumentation , Dosage Forms , Food-Drug Interactions , Humans , Hydrogen-Ion Concentration , Intestinal Absorption , SolubilityABSTRACT
This paper describes the development and validation of a rapid, direct, and stability-indicating method for analysis of etidronate, a bisphosphonate compound without a UV chromophore. A mixed-mode column was used to separate etidronate from its impurities in an 8-min gradient method and a charged aerosol detector (CAD) was used for detection. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, and stability. The method can be used for release and stability testing of etidronate and has applicability to other similar bisphosphonate compounds.
