Primer on the Science of In Vitro Dissolution Testing of Oral Dosage Forms and Factors Influencing its Biological Relevance

Abstract

In vitro dissolution testing can serve as an effective and efficient tool for evaluating the influence of formulation and manufacturing variables on drug release characteristics. The targeted purpose will determine the method used and the implications of the test results. Regardless of its intended purpose, it is necessary to understand the factors influencing in vitro dissolution outcomes to avoid the introduction of error into the data interpretation. This will influence the selection of the in vitro test procedure, ensuring that the method can identify changes in the critical formulation and manufacturing variables. There is also a need to understand the rate limiting factors influencing in vivo product bioavailability both from a dissolution and an absorption perspective. Finally, to achieve in vivo biorelevance, it is necessary to understand how the selected in vitro dissolution test method reflects the variables impacting in vivo product dissolution behavior. This primer summarizes and integrates these diverse variables, fostering an appreciation of the strengths and potential pitfalls that may be encountered during the generation and analysis of in vitro dissolution profiles associated with oral dosage forms. This understanding is needed for developing a well-designed dissolution test procedure that is appropriately fit for purpose.

The development of an innovative method to improve the dissolution performance of rivaroxaban

“…Under fasting conditions, its bioavailability decreases by up to 66 % when administered at high doses, whereas dose proportionality and had high oral bioavailability were obtained for all doses under fed conditions [ 92 ]. In-vitro dissolution testing is a useful tool to assess the variables that affect the rate and extent of drug release from drug products and therefore serve as a substitute for bioavailability studies [ 93 ]. The USP dissolution test conditions for RIV recommend the addition of sodium lauryl sulfate (SLS) to the dissolution medium to ensure the sink condition when testing RIV tablets of 10 or 20 mg [ 53 ].…”

Evaluation of Different Methods for Dissolution Profile Similarity Comparison of Montelukast Tablets in Türkiye

“…In the current study, despite in vivo bioequivalence being established for the generic MS tablets in 0.5% SDS, similarity with the innovator product could not be established based on dissolution profiles using Bootf2BCA and PhEq_bootstrap methods. Possible reasons for the observed differences are that the dissolution medium might not be sufficient to show differences or similarities in the drug release profile, and/or the dissolution method (with USP apparatus 2) may not fully reflect the in vivo conditions for pH-dependent, poorly water-soluble, firstpass metabolism-exposed drugs such as MS (34,35).…”