Dissolution Media l FDA Database l pH Range l Temperature

                                         

Dissolution Media

The dissolution profile test is one of the most useful methods used in different stages of the drug product lifecycle: pharmaceutical development, stability studies, interchangeability evaluation, routine quality control, and scale-up and post-approval changes.

The Food and Drug Administration Dissolution Database is open access and is updated on a quarterly basis. There were 1350 drug products in the database at the time of search (Jan 2021). The database provides information on drug products in terms of International Nonproprietary Name (INN), dosage form, USP apparatus type, speed (rpm), dissolution medium, volume, sampling time points, and date of latest update. The database is one of the most accessible, suitable, full, and informative resources on dissolution. Refer below link to get the dissolution /dissolution method information for any particular drug product.

https://www.accessdata.fda.gov/scripts/cder/dissolution/dsp_getalldata.cfm

  

The FDA Dissolution Database describes a large number of different media, from water or simple buffer solutions with different pH values to solutions with added surfactants, organic solvents, and enzymes.

pH Range of Dissolution Medium

The most common dissolution media in the database have pH values in the range of 1–7.5 (i.e., 1.2, 2, 4, 4.5, 5, 6, 6.8, 7.2, and 7.5). These pH values are found in the GI tract and are considered physiologically relevant.

It is important to note that FDA database methods are primarily developed to determine in vitro dissolution profiles of drug products; therefore, these media may not reflect in vivo physiological conditions in some cases. Nowadays the agency is emphasizing the discriminatory power of the method. It does not have to mimic what happens in vivo, but it must be discriminatory for the critical quality attributes. For this reason, the FDA database describes eight media whose pH values are outside the physiological parameter range (e.g., pH 12 for Celecoxib Capsules, pH 9.5 for Glyburide Tablets, pH 8.0 for Rabeprazole Sodium Tablets and Proguanil Hydrochloride Tablets; pH 7.8 for Glimepiride Tablets, Azilsartan Kamedoxomil Tablets, and Tretinoin and Isotretinoin Capsules).

Dissolution Medium - Acidic in nature

According to the database, several aqueous solutions of acids could be used as dissolution media. The most commonly used acidic media are based on hydrochloric acid: 0.1 М, 0.01 М, and 0.001 М HCl. Phosphoric acid (0.01 М) and other acidic solutions may also be used.

 

Dissolution Medium – Basic in nature

Various buffer solutions (acetate, citrate, and phosphate) are recommended for dissolution testing in mildly low pH. Dissolution media with high pH values are prepared by adding sodium hydroxide solution, borate buffers, and Tris buffers.

Dissolution Medium with Surfactant

For water-insoluble or sparingly soluble drug products (BCS Class II or IV), the use of a surfactant (about 18.5% of methods) such as sodium lauryl sulfate, Tweens (polysorbate 20 and 80), lauryl dimethylamine oxide (LDAO), Triton X, Brij 35 (polyoxyethylene lauryl ether), cetyl trimethyl ammonium bromide (CTAB), and others (Figure 3) is recommended. The most commonly used surfactant is sodium lauryl sulfate (SLS, SDS); its concentrations are reported in the range of 0.01–3%.

Dissolution Medium with Organic compounds

Dissolution media in the database may contain enzymes. The addition of enzymes may be considered, for example, for formulations containing gelatin in the outer layer (e.g., hard and soft gelatin capsules) (4). Pepsin solution in hydrochloric acid is used for the dissolution of dutasteride, loratadine, imipramine pamoate, enzalutamide, and emtricitabine capsules. Addition of pancreatin to the dissolution medium is recommended in the cases of dissolution of ibuprofen, bexarotene, and pseudoephedrine hydrochloride capsules.

Dissolution Medium with Enzyme

In some specific cases, the use of organic compounds is recommended. For instance, a medium containing 40% isopropanol is used in the method for Atovaquone Tablets. A medium containing 5% methanol is recommended for the injectable suspension of Triptorelin Pamoate. The necessity of an organic solvent for the dissolution test in these formulations is associated with the extremely low water solubility of atovaquone (<0.2 µg/mL) and triptorelin pamoate.

Volume of Dissolution Medium

Dissolution medium volume – Range 500 – 1000 mL

The volume of the dissolution medium is generally in the range of 500–1000 mL. The most commonly used volumes are 900 mL (about 56% of methods), 500 mL (about 12% of methods), and 1000 mL (about 10% of methods). Volumes of 750 mL and 600 mL often occur in methods that require a pH change of the dissolution medium.

Dissolution medium volume less than 500 mL

In specific cases, the FDA database recommends a volume less than 500 mL (e.g., 400 mL for Diclofenac Potassium Suspension). A decrease in dissolution volume is often dictated by the need to increase the sensitivity of quantitative determination methods and obtain dissolution profiles for low doses of drug products. For example, the database recommends Apparatus 1 and 2 that are specially adapted for small volumes of dissolution medium (60–200 mL) for buccal tablets and films of fentanyl at doses of 0.1–1.2 mg.

Temperature of Dissolution Medium

Most dissolution tests in the FDA database should be conducted at 37 ± 0.5 °C.

The temperature of the dissolution medium is specified in cases where it differs from 37 °C. Generally, the temperature of the medium should be the same as the temperature of the application site of the product. The most commonly used temperature for topical dosage forms is 32 °C.

In cases of certain extended-release dosage forms where the product will remain at the site of application for a long time, generally for several months, it may be possible to reduce the duration of the dissolution test if the temperature of the test is greater than 37 °C. The test temperature is 45 °С for Dexamethasone Implant (intravitreal), 40 °С for Mesalamine Suppository, and 38 °С for Prochlorperazine Rectal Suppository.

The temperature of the dissolution medium may also be less than 32 °С. For instance, it is 25 °С for oral suspensions and tablets of nitazoxanide and injectable suspensions of paliperidone palmitate.