Dissolution Testing Services

The experience and knowledge-based dissolution method development platform within Avivia focuses primarily on supporting formulation development and problem solving. For dissolution method development, ideally, clinical data will be used for fine-tuning and validation of dissolution method(s) to ensure discriminatory dissolution method development and biorelevant dissolution testing. For us dissolution testing is never a routine test but an essential tool in pharmaceutical formulation development to:

• evaluate the physico-chemical properties of drug candidates to select the most appropriate solid form for further development (pre-formulation)
• compare prototype formulations (preclinical selection),
• elucidate drug release mechanism (diffusion, erosion, etc.)
• as an indicator of stability (e.g., temperature, humidity)
• as an indicator of the robustness of the manufacturing and
• assure safe release and reproducibility of the products to the market.

Dissolution testing in pharmaceutical industry is to be a discriminatory method that is sensitive to variables that impact the release rate and ideally is predictive of bio-performance.

Dissolution Apparatus Equipment

Within Avivia dissolution testing services we have the complete range of dissolution testing equipment available:

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

Pion µDiss Profiler (low volume in situ fiber optic UV monitoring dissolution and solubility system)
 
Avivia dissolution laboratory
 
As intrinsic dissolution apparatus both the Pion µDiss Profiler and Wood apparatus are present, while specific cells for flow through cell dissolution apparatus are used for testing the apparent dissolution of powders like granules and active pharmaceutical ingredients (API).
 
And when required, other less common or more academic techniques are accessible in our network.
 

But most important we know how and when to apply all these systems in support of formulation development, troubleshooting and optimization.

Dissolution Method Development

The development of a discriminatory dissolution method, or a coherent program of dissolution methods, combines information about:

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 years of experience and knowledge about the different disciplines involved.

 

Teamwork

At Avivia we work in small multidisciplinary pharmaceutical expert teams, allowing the analytical researcher to be directly involved in the process of formulation development.

In this setting, method development of dissolution methods will be more effective 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 valuable 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 additional guidance in the evaluation of dissolution profiles, release mechanisms, excipient performance and setting process parameters.

in-vitro in-vivo correlation (IVIVC)

In cooperation with our clinical research partners we have successfully established in-vitro in-vivo correlations (IVIVC) for several modified release dosage forms.

USP Apparatus III

Reciprocating Cylinder/BioDis in action

USP IV

Flow Through Cell apparatus

USP IV

Different types of flow cells:

(from left to right)

– Flow cell for powders and granules

– Flow cell for small tablets

– Flow cell for large tablets

Observations

USP Apparatus II Paddle

Observations of a matrix tablet provides additional information about

– hydration

– swelling

– erosion

More than performing a dissolution test

Evaluation of the formulation after the dissolution test

– compare the results of different tests

– helps to understand dissolution results

– provides valuable additional information

More than performing a dissolution test

Evaluation of the tablet remains after a BioDis dissolution test

– compare the results of different tests

– helps to understand dissolution results

– provides valuable additional information