Discriminatory dissolution profiles
Drug dissolution profiles are increasingly used to evaluate drug release characteristics of pharmaceutical products. The dissolution
media adopted by the pharmacopoeias or recommended by the FDA for in vitro dissolution testing are designed to maximize drug release for a given drug. Thus, for a given marketed drug, the recommended
medium becomes the quality control standard to assure batch to batch consistency, and ensure continuing product quality and
performance are maintained should changes be made to the manufacturing process.
Although the recommended media for in vitro dissolution testing can be used to guide formulation development, it is typically nondiscriminatory between formulation ingredients,
as drug release with a poorly soluble drug is usually driven more by the medium than by formulation ingredients.
Discriminatory dissolution profiles are highly desirable for distinguishing between products with differences in pharmaceutical
attributes (formulation and/or manufacturing process differences).5
In the present study, dissolution testing was conducted in the recommended media for the drug (the US Pharmacopeia or FDA
recommended medium), as well as in modified dissolution media designed to produce drug release profiles that discriminate
between formulations with different superdisintegrants. The discriminating media were selected with at least one formulation
achieving 80% drug release. The recommended and discriminating media for each drug tested are shown in Table 2.
Table 2: Dissolution media tested for drugs with varying degrees of aqueous solubility.
Tablet physical properties
For a given drug, the formulations were produced using the same process, ingredients and ingredient levels. Tablets were prepared
at the highest market dose using a direct compression or wet granulation process, as considered appropriate through a review
of the ingredients listed in the Physician's Desk Reference and patent literature. In addition, tablets were compressed to equivalent tablet breaking force to minimize the impact of
the tablet's physical properties on the dissolution results. Only the selection of superdisintegrant varied.
With the 13 poorly soluble drugs evaluated, no significant differences were observed in the breaking force and disintegration
times of the tablets prepared using the various superdisintegrants for a given drug studied. The full results can be viewed
Choice impacts dissolution
The t80 results for all 13 drugs studied in both media are shown in Table 3. As examples, the dissolution profiles for the tablets with atorvastatin in the recommended and discriminating media are
shown in Figures 1 and 2.
Table 3: T80 values of drugs tested in different dissolution media.
In the recommended media, crospovidone Type A and Type B provided the fastest t80 for 12 of the 13 drugs studied, while crospovidone Type B provided the fastest t80 for 10 of the 13 drugs studied.
Figure 1: Dissolution profile for 80 mg Atorvastatin tablets in recommended media.
In the discriminating media, crospovidone Type B provided the fastest release for 12 of 12 drugs — a discriminating medium
for raloxifene HCl tablets was not developed as the recommended medium was sufficiently discriminating; hence only 12 drugs
were evaluated in a discriminatory medium.
Figure 2: Dissolution profile for 80 mg Atorvastatin tablets in discriminating media.
The dissolution profiles indicate that the tablets with crospovidone Type B in both the recommended and discriminating media
had the fastest rate of dissolution.