Now you can overcome the severe limitations of current dissolution approaches for orally inhaled drug products (OIDPs) and significantly increased the reliability, ruggedness and discriminatory capability in the dissolution measurements with our Dissohale technology.
Dissohale constitutes a significant step change towards gaining a better understanding of the relationship between raw materials critical material attributes and drug product performance. The advent of the Dissohale technology will help support the development of OIDPs using a quality-by-design (QbD) approach that can be used for:
- Formulation development and optimization
- Product quality control
- Determining characteristic changes of a product over time
- Facilitating certain regulatory determinations (e.g. absence of effect of minor formulation changes or of a change in manufacturing site on structure
- Indicating how a formulation may perform in vivo.
- Current Collection System Graph
- Current Dose Collection - 5 shot filter
The major challenge in developing a predictive in vitro dissolution method is the collection of a representative inhalable dose and the dissolution step of dissolving the collected dose.
Dissolution measurements need to be independent of the method of collection and the loaded dose. For a whole range of different approaches, slower relative dissolution rate is observed with increasing mass loading (typically achieved by varying the number of actuations). The absence of this consistency in the dissolution rate measurements within current systems is thought to be directly attributable to an artefact of the collection process itself. These systems limit sensitivity and creates a challenge when comparing formulations with differing fine particle dose.
The approach View Nanopharm Site
- New Unidose Collection System
To overcome the limitations of current collection systems, we have developed a proprietary aerosol dose collection system – UniDose™. The UniDose™ uniformly deposits the whole in vitro lung dose (e.g. ex-cast dose, impactor stage mass etc.) directly onto a high surface area filter membrane under laminar flow and low impaction velocity.
The uniformity of deposition on the filter surface of the UniDose is illustrated upon increasing number of actuations of a red ink dye, which has been formulated as a solution MDI.
The drug loaded filters can be subsequently used for dissolution studies with a standardized, compendial dissolution test apparatus such as Franz cell, USP IV flow through, USP V Paddle over Disk apparatus etc.
The solution View Nanopharm site
This uniform dosing achieved with the UniDose apparatus leads to an independence of drug loading on dissolution characteristics. This has been demonstrated for both carrier based DPI and suspension based MDI formulations with varying number of actuations and loaded mass.
In overcoming the severe limitations of current collection systems, our Dissohale technology has increased the discriminatory capability in determining dissolution differences of OIDPs.
Our in vitro predictive dissolution model can study the effect of formulation factors (drug particle size, formulation composition, etc.) on dissolution of aerosolized drug particles and thereby gain possible in vitro-in vivo relationships for orally inhaled drugs.