Drug Dissolution Testing - GLP

Contact us for help with dissolution studies of your drug compound.

Drug absorption from a solid dosage form (tablet, capsule) after oral administration depends on:

• the release of the drug substance from the drug product
• the dissolution or solubilization of the drug under physiological conditions
• the permeability across the gastrointestinal tract

Because of the critical nature of the first two of these steps, in vitro drug dissolution is predictive of in vivo performance. Based on this general consideration, in vitro drug dissolution tests for immediate-release tablets and capsules are used to:

• guide development of new drug formulations
• assure conformity of a drug product to its specifications and its lot-to-lot quality

Knowledge of the dissolution properties of a drug should be considered in defining dissolution test specifications for the drug approval process. This knowledge should also be used to ensure continued bioequivalence of the drug, as well as to ensure the drug's sameness under scale-up and post-approval changes. Acceptable bioequivalence and comparable in vitro dissolution data should submitted to the FDA together with Chemistry, Manufacturing, and Controls (CMC) data to characterize the quality and performance of the drug, as these are required for FDA approval of new-drug applications (NDAs) and abbreviated new-drug applications (ANDAs) (21 CFR 314.94).

FDA Drug Dissolution Study Requirements

For approval, all new drugs should meet current USP dissolution test requirements, if they exist. The approaches for setting dissolution specifications for generic drugs fall into three categories, depending on whether an official compendial test for the drug product exists, and on the nature of the dissolution test employed for the reference listed drug:

1. USP Drug Product Dissolution Test Available
2. USP Drug Product Dissolution Test Not Available; Dissolution Test for Reference Listed NDA Drug Product Not Publicly Available
3. USP Drug Product Dissolution Test Not Available; Dissolution Test for Reference Listed NDA Drug Product Publicly Available. In this instance, a dissolution profile at 15-minute intervals of test and reference products (12 units each) using the method approved for the reference listed product is recommended.

The FDA's Division of Bioequivalence may also request submission of additional drug dissolution testing data as a condition of approval, when scientifically justified. For further information, see Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), August 1997.

Drug Dissolution Analysis

Generally, drug dissolution is measured below saturation, at 37ºC in water or aqueous based buffers (pH range of 1 to 7) in a dissolution apparatus under precisely controlled mechanical and operational parameters. Depending on the nature of the drug (and in accordance with a developed and validated protocol), the tests are conducted for various durations from 15 minutes to 24 hours with appropriate sampling. The results of the dissolution analysis are reported as cumulated percent drug dissolved at specified time intervals.

Apredica's drug dissolution studies are performed in partnership with BioVolutions, in a GLP-certified lab.

Contact us if you need a CRO to provide a dissolution study of your drug compound.