Pharmacy Courses

What is the Intrinsic Dissolution Rate and Why It is so Important?


Going back to the Noyes-Whitney equation below, we see that the dissolution rate is correlated to the intrinsic dissolution rate.  

The intrinsic dissolution rate is how quickly the pure drug substance (API) dissolves in a media under controlled conditions.  

The intrinsic dissolution rate can be performed by either putting the API directly into the dissolution vessel (particulate method) or using something like the Woods Apparatus in the slide below to contain and control the API (constant surface method).  The constant surface method is preferred because it limits the impact of variables - primarily surface area (S), but also electrical charges.

The intrinsic dissolution rate can help determine your BCS class, identify optimal dissolution medias, and guide API selection.  To get your intrinsic dissolution rate, you would load your API into the intrinsic dissolution device, compress it, and then put it on your dissolution system as you would a paddle or basket shaft.  Perform your dissolution, and take samples at relatively quick intervals.  The data of interest will begin after the initial wetting until about 10-20% of your drug has dissolved.  In between this area, we should see minimal impacts from surface area changes as well as little slowing of the dissolution rate due to what has already dissolved (Cs-Ct).  This rate should be fairly linear - and is your intrinsic dissolution rate.

Rates above 1.0mg/min/cm2 are considered highly soluble and generally don't present issues with dissolution rate limitations.  Rates below 0.1mg/min/cm2 are considered poorly soluble and will likely have challenges with dissolution rate limitations.  If you are between 0.1-1, then you are considered soluble, but in this middle area you don't necessarily know if the dissolution or absorption will be the rate limiting step.

The intrinsic dissolution rates can be helpful to guide which API will be used in the final dosage form.  The closer the intrinsic rate is to the target formulation rate, the less work the excipients will need to do!  The rate can help guide media selection in finding optimal pHs for testing.  You can really gain a lot of information from this simple test to help guide dissolution method development and formulation development.

Resource Person: Ken Boda

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