Choosing a Medium and Volume for Dissolution Testing....

Choosing a Medium and Volume

When choosing a dissolution medium, several factors need to be considered:

1. Solubility: The medium should be able to dissolve the drug substance to a sufficient extent.
Solubility studies should be conducted to determine the solubility of the drug substance in
different media. The chosen medium should have a solubility that allows for accurate and reliable
dissolution testing.
2. Sink Conditions: Sink conditions should be maintained during dissolution testing. This means
that the volume of the medium should be at least three times the volume required to form a
saturated solution of the drug substance. Sink conditions ensure that the dissolution results reflect
the true dissolution behavior of the dosage form.
3. pH: The pH of the dissolution medium should be appropriate for the drug substance. Some drugs
may have pH-dependent solubility, and it is important to select a medium with a pH that mimics
the physiological conditions in which the drug will be administered.
4. Stability: The medium should not cause degradation or instability of the drug substance. Care
should be taken to ensure that the drug remains stable throughout the dissolution analysis. In
some cases, antioxidants or stabilizers may need to be added to the medium to maintain the
stability of the drug.

When developing a dissolution procedure, it is important to choose an appropriate medium and volume
for the test. The goal is to have sink conditions, which means that the volume of the medium should be at
least three times the volume required to form a saturated solution of the drug substance. Sink conditions
ensure that the dissolution results accurately reflect the properties of the dosage form.

The appropriate composition and volume of the dissolution medium should be determined based on
solubility investigations. These investigations will provide information on the solubility of the drug
substance in different media. The chosen medium should be able to maintain sink conditions and provide
accurate dissolution results.

If the use of surfactants is necessary, it should be justified by data showing low solubility of the drug
substance in aqueous media. The concentration of the surfactant should also be justified by providing
dissolution profiles in media with higher and lower concentrations of the surfactant.
Critical Micelle
Surfactant Concentrations (CMC)
(% wt/volume)
 Sodium dodecyl sulfate (SDS) 0.18–0.23%
 Sodium lauryl sulfate (SLS) 0.18–0.23%
Anionic  Taurocholic acid sodium salt 0.2%
 Cholic acid sodium salt 0.16%
 Desoxycholic acid sodium salt 0.12%
 Cetyltrimethyl ammonium bromide (CTAB, 0.033%–0.036%
Cationic Hexadecyltrimethylammonium bromide) (0.92–1.0 mM)
 Benzethonium chloride (Hyamine 1622) 0.18%(4 mM)
Nonionic  Polysorbate 20 (Polyoxyethylene (20) sorbitan monolaurate
0.006%–0.093%
Tween 20)
 Polysorbate 80 (Polyoxyethylene (80) sorbitan monooleate, 0.002 %0.082%
Tween 80)
  Caprylocaproyl polyoxyl-8 glycerides (Labrasol) 0.01%
 Polyoxyl 35 castor oil (Cremophor EL) 0.02%
 Polyoxyethylene 23 lauryl ether (Brij 35) 0.013%
 ZwitterionLauryldimethylamine N-oxide (LDAO) 0.023%

Enzymes can be used in the dissolution medium if dissolution failures occur due to cross-linking with
gelatin capsules or gelatin-coated products.

Another option is to use media that closely resemble the fluids in the stomach and intestinal tract. These
media may contain physiological surface-active ingredients, emulsifiers, and components that increase
osmolality. The ionic strength or molarity of the buffer solutions may also be manipulated. These media
are useful for modeling the in vivo dissolution behavior of immediate-release dosage forms, especially
those with lipophilic drug substances.

For delayed-release products, an acid stage is included in the testing. However, for poorly acid-soluble
drugs or drugs that degrade in acid, detecting the drug may be challenging. In such cases, the addition of
surfactant to the acid stage or adjustment of specifications may be necessary.

During the selection of the dissolution medium, stability of the sample should be considered.
Antioxidants like ascorbic acid can be used to stabilize the drug in some cases. In other cases, monitoring
the degradation product alone or in combination with the drug substance may be more suitable.

The volume of the dissolution medium can vary depending on the apparatus used. For compendial
Apparatus 1 (basket) and Apparatus 2 (paddle), the volume can range from 500 to 1000 mL, with 900 mL
being the most common. The volume should be determined to maintain sink conditions. In some cases,
larger volumes (2-4 L) may be used with larger vessels, depending on the concentration and sink
conditions of the drug. Justification for this approach is expected.

Alternatively, other compendial apparatus such as a reciprocating cylinder (Apparatus 3), reciprocating
holder (Apparatus 7), or flow-through cell (Apparatus 4) can be used. In certain applications, low
volumes of dissolution media (100-200 mL) may be required, and in such cases, noncompendial
apparatus like a small-volume apparatus can be used.