Dissolution

For us dissolution testing is never a routine test but an essential tool in pharmaceutical formulation development to:

• evaluate the physicochemical 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 is to be a discriminatory method that is sensitive to variables that impact the release rate and ideally is predictive of bio-performance.

Equipment

Within Avivia we have a complete array of dissolution testing equipment available:

USP apparatus I (Basket)
USP apparatus II (Paddle)
USP apparatus III (Reciprocating Cylinder/BioDis)
USP apparatus IV (Flow Through Cell)
Pion µDiss Profiler (in situ fiber optic UV monitoring dissolution and solubility system)

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 of these systems in support of formulation development, troubleshooting and optimization.

Development

The development of such 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.)
Process type (blending, granulation, drying, tableting, coating, etc.)
Process variables (adding, speed, time, temperature, water, 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 expert teams, allowing the analytical researcher to be directly involved in the process of formulation development.

In this setting, effective dissolution methods can be developed and significantly more important information can be derived from the 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 observations during interactions with the pharmaceutical developer offers additional guidance in the evaluation of dissolution profiles, release mechanisms, excipient performance and setting process parameters.

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 system

USP IV

Different types of flow cells:

(from left to right)

– Flow cell for powders and granulates

– 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