Dissolution Method Development

Teamwork

At Avivia we work in small multidisciplinary pharmaceutical expert teams. This allows the analytical researcher to be directly involved in the process of formulation development and interact with clinical R&D.

This way of working is essential for effective dissolution method development. In this setting, dissolution method development will be more successful and significantly more important information can be derived from each dissolution test.

Educated observations made by the researcher during, and at the end of the dissolution test, provide extremely valuable additional data about disintegration, hydration, swelling, erosion, particles size, granulation and coating properties, floating, cone formation, sticking, etc.

Discussing these dissolution observations during interactions with the pharmaceutical developer, offers extremely important additional guidance in the evaluation of dissolution profiles, release mechanisms, excipient performance, formulation composition, setting process parameters and to fine-tune the dissolution method itself.

Preferably, (pre)clinical data will be evaluated, discussed and used to support dissolution method development and adjust or validate dissolution method(s). 

More than performing a dissolution test
Evaluation of the formulation after the dissolution test

Comparing the results of different tests helps to interpret dissolution results, formulation performance and provides valuable additional information
USP Apparatus III observations
Evaluation of the tablet remains after a BioDis dissolution test.

Product remains can be evaluated on e.g. appearance, dimensions, mass and drug content
USP apparatus IV observations
Zooming in on the disintegration process of immediate release products

A powerful tool to observe and compare different batches at the same time
USP Apparatus II Observations
Observations of a matrix tablet provides additional information about:

hydration, swelling, erosion, release
USP Apparatus III observations
Evaluation of excipient release during and after a BioDis dissolution test.

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Dissolution Method Development

In dissolution method development, information from different disciplines in the team is collected, combined and processed into dissolution methods:

 

Active pharmaceutical ingredient (API):  dose, morphological form, wetting, particle size, intrinsic solubility, hydrophobicity, pKa, etc.

Excipients:  function, properties, type, grade, particle size, etc.

Pharmaceutical process type:  blending, granulation, drying, tableting, coating, etc.

Process variables:  adding, speed, time, temperature, solvent, compression force, spraying time, etc.

Dosage form:  tablet, capsule, suspension, powder, cream, patch, rod, multi particulate, etc.
 
Dosage design:  matrix, floating, osmotic, erosion, stimuli inducing release, etc.
 

Time release technology:  delayed release, extended release, immediate release, timed release, etc.

Route of administration:  oral, buccal, sublingual, rectal, injection, etc.

Pharmacokinetic properties:  absorption, distribution, metabolism, excretion

Clinical study program:  fasted, fed, timing, volumes, etc.

 

To link all this information together, extract the critical parameters and translate this to a relatively simple in-vitro test, requires extensive knowledge about the different disciplines involved.

Years of experience help us in selecting the most appropriate dissolution technique, method parameters and dissolution media to come to a selective bio-relevant set of dissolution methods.

Ultimately, from knowledge, a suitable discriminatory QC release method will be extracted and selected.

Dissolution Equipment

To facilitate dissolution method development a complementary range of dissolution testing equipment is available within the Avivia dissolution laboratory:

USP apparatus 1 / Basket dissolution apparatus
USP apparatus 2 / Paddle dissolution apparatus
USP apparatus 3 / Reciprocating cylinder dissolution apparatus / BioDis
USP apparatus 4 / Flow through cell dissolution apparatus

Pion µDiss Profiler (low volume in situ fiber optic UV monitoring dissolution and solubility system)

 We know from experience what the strengths are of each technique, and how we can best apply them to highlight and optimize the most relevant properties of each formulation.

If desired, other less common or more academic dissolution testing techniques are accessible in our network, or we design a tailor-made dissolution setup with, for example, glass fiber optic probes and semi permeable membranes.