AEROPERL® 300 Pharma – Improving the dissolution of poorly soluble APIs

Active pharmaceutical ingredients (APIs) by Evonik in oral dosage forms need to dissolve before they can be absorbed in the intestine to enter the systemic circulation. Therefore, both the dissolution of the APIs, as well as the permeation of the dissolved API through the intestinal membrane into the systemic circulation are important processes to reach the required blood concentration for the API to become effective. A high dissolution rate of the API in the intestinal fluid can positively influence permeation rates.

The importance of drug dissolution and permeability is reflected by the Biopharmaceutics Classification System (BCS) originally proposed by Amidon, which groups the APIs into four different classes according to their permeability and solubility in aqueous media (see Figure 1).

Drugs categorized in class II of the BCS system primarily
suffer from poor aqueous solubility, which therefore is
the limitation to achieve therapeutically necessary blood
concentrations.

Changes in the way new chemical entities are developed and identified have led to a situation where many of the possible API innovations have poor aqueous solubility. Although numbers deviate by source, there is general agreement that many new drug candidates, and even more coming from synthesis, face aqueous solubility challenges. According to a recent survey, drug solubility and bioavailability are the most important formulation challenges in pharmaceutical development. Insufficient solubility may lead to the abandonment of an otherwise promising new chemical entity.

Unfortunately, no single formulation approach can solve the issue of poor aqueous solubility for all actives and innovative concepts from academia can be hard to implement at a commercial scale. Formulators in the pharmaceutical industry have limited freedom as they need to consider the availability of technical equipment in the plants as well as production costs.

In the previously mentioned survey, several technologies for the improvement of formulations with APIs having low aqueous solubility are listed. Among these, API crystal micronization, solid dispersions and lipid-based drug delivery proved to be more successful.

AEROPERL® 300 Pharma is a member of the AEROSIL® Pharma colloidal silicon dioxide family. AEROPERL® 300 Pharma features all the advantages of the AEROSIL® Pharma silicon dioxides such as:

• Composed of purely amorphous synthetic silicon dioxide
• High purity precursors, therefore extraordinary low elemental contamination levels
• No organic or biogenic material used in production, therefore no contaminations with these kind of material
• Tested against the high quality requirements of monographs “Silica Colloidal Anhydrous” (Ph. Eur.) and “Colloidal Silicon Dioxide” (USP/NF)
• GMP production according to the guideline of IPEC16
• Production audits available on request according to an annual schedule

However, unlike the fluffy and often dusty AEROSIL® Pharma powders AEROPERL® features a greatly increased density as it consists of round shaped granules in the range of 20–60 μm. Figure 2 shows the particle shape of the material in a scanning electron microscopy image. In Figure 3 the difference in density of 8 g of AEROPERL® 300 Pharma compared to the same amount of AEROSIL® 200 Pharma is shown.