AEROSIL® Pharma, the reference glidants: from classic tableting to continuous manufacturing
The Formulation Challenge: Why Powder Flow Cannot Be an Afterthought
Every pharmaceutical manufacturer working with solid dosage forms — whether tablets, capsules, or sachets — understands that a formulation that looks perfect on paper can fail catastrophically on the production floor. The culprit, more often than formulation scientists would like to admit, is powder flow.
Poor flowability is not just an inconvenience. It drives tablet weight variability, out-of-specification batches, and costly production stoppages. In an environment where health care cost pressure grows relentlessly and regulatory scrutiny of content uniformity has never been higher, suboptimal powder flow translates directly into financial and compliance risk.
The underlying physics are well understood. Particles in a powder blend experience a constant tug-of-war between gravity — which drives flow — and attractive interparticle forces that resist it. Two types of force dominate in practice:
- Van der Waals forces, which scale inversely with the square of the distance between particle surfaces. Fine powders and micronized APIs are particularly susceptible because the particle-to-particle distances are inherently small.
- Liquid bridges, which form when moisture gathers in particle pores or on surfaces. Even modest humidity can create capillary bonds strong enough to make a previously free-flowing blend cohesive.
The challenge intensifies as particle size decreases. Crystal micronizsation, increasingly used to improve the dissolution of poorly soluble APIs and to ensure dose uniformity in highly potent formulations, systematically worsens flow. A glidant that can intervene at the particle surface level is therefore not optional — it is structurally necessary. For tackling solubility challenges of poorly water soluble API´s Evonik is offering the mesoporous silica carrier product AEROPERL® 300 Pharma. AEROPERL® 300 Pharma increases the dissolution of poorly liquid and solid API`s, in continuous or batch processes. For more info please click bellow to download our AEROPERL® 300 Pharma one pager !
Key Formulation Problem
Fine and micronized powders, moisture-sensitive APIs, and continuous manufacturing lines all share one common vulnerability: they are severely impacted by inadequate powder flow. A glidant that addresses both van der Waals or capillary forces — while remaining compatible with high-speed and continuous equipment — is essential to protect batch quality and manufacturing efficiency.
AEROSIL® 200 Pharma: The Reference Standard in Pharmaceutical Glidants
Developed by Evonik, one of Azelis's Trusted Partners, AEROSIL® 200 Pharma is a pharmaceutical-grade silicon dioxide (Silica colloidalis anhydrica) manufactured by flame hydrolysis — a continuous, high-purity gas-phase process. The reaction involves the hydrolysis of silicon tetrachloride in a hydrogen-oxygen flame.
Because the process relies exclusively on inorganic raw materials — no metal catalysts, no organic solvents, no biogenic materials — the resulting powder achieves a silicon dioxide purity exceeding 99.8% by weight. Elemental impurity levels fall below the ICH Q3D Option 1 thresholds, making AEROSIL® 200 Pharma compatible even with APIs that are highly sensitive to heavy metal contamination.
The material's three-level particle architecture — constituent particles, aggregates (held together by covalent bonds), and agglomerates (held by van der Waals and hydrogen bonds) — is key to its mechanism of action. When blended into a powder mixture, the agglomerates break down and the silica particles distribute across the surface of host powder particles, physically separating them and reducing both van der Waals attractions or moisture-mediated bridges.
Key Physical Properties
Property | Value / Specification |
|---|---|
Type | Powder (hydrophilic) |
Specific Surface Area (BET) | 175 – 225 m²/g |
Tamped Density | approx. 50 g/L |
pH (4% aqueous dispersion) | 3.5 – 5.5 |
SiO₂ content (dried substance) | > 99.8% |
Behaviour in water | Hydrophilic |
Pharmacopoeia Compliance
AEROSIL® 200 Pharma offers comprehensive compliance with all major pharmacopoeias simultaneously, providing unmatched regulatory flexibility across global markets.
Pharmacopoeia | Monograph | Status |
|---|---|---|
Ph. Eur. | Silica, Colloidal Anhydrous (monograph 0434) | ✓ Compliant |
USP/NF | Colloidal Silicon Dioxide | ✓ Compliant |
JP | Light Anhydrous Silicic Acid | ✓ Compliant |
IP (India) | Colloidal Silicon Dioxide | ✓ Compliant |
ChP (China) | Colloidal Silicon Dioxide (Jiaotai Eryanghuagui) | ✓ Compliant |
Manufacturing is conducted in full compliance with IPEC GMP guidelines for pharmaceutical excipients, with complete raw material traceability, stringent hygiene protocols during bag filling, and certificates of analysis certified against pharmacopoeial requirements.
Safety Profile and Regulatory Status
AEROSIL® 200 Pharma has been used safely as a pharmaceutical excipient for over 60 years. Its synthetic amorphous structure is fundamentally different from crystalline silica and does not cause silicosis. Based on available toxicological data:
- Acute oral LD50 > 10,000 mg/kg (rat)
- Not irritating to skin or eyes (rabbit)
- No evidence of genotoxic, carcinogenic, or reproductive toxicity
- Not significantly absorbed from the gastrointestinal tract
- Inert towards the vast majority of APIs and excipients
Note: AEROSIL® 200 Pharma is not recommended for parenteral delivery or drug delivery by inhalation routes. Adsorption of active components onto the silica surface is possible but typically reversible and low in magnitude.
From a regulatory standpoint, AEROSIL® 200 Pharma is registered across all major chemical substance inventories (REACH, TSCA, DSL, IECSC, and others). It is listed with a monograph in most relevant pharmacopoeias and is fully compliant with IPEC GMP guidelines. Kosher and Halal certificates, BSE/TSE and GMO standard statements are available on request. The production process involves no plant, animal, or biogenic raw materials and no organic solvents.
Regulatory Attribute | Status |
|---|---|
IPEC GMP compliance | Full — manufacturing, traceability, hygiene protocols |
Ph. Eur. / USP-NF / JP / IP | All four monographs: compliant |
ICH Q3D elemental impurities | Below Option 1 threshold values |
REACH registration | Registered (EINECS 231-545-4) |
BSE/TSE statement | Available on request |
Kosher / Halal certificates | Available on request |
GMO statement | Available on request |
How AEROSIL® Pharma Solves the Flow Problem
Mechanism 1: Reducing Van der Waals Forces in Dry Powders
When AEROSIL® Pharma is mixed with a host powder, its silica particles — once the agglomerates are broken down by mixing shear — adsorb onto the surface of the host particles. This creates a physical separation effect: the effective centre-to-centre distance between host particles increases, which according to the Hamaker equation causes a sharp reduction in van der Waals attractive forces. The net result is a powder blend where gravity can overcome interparticle attraction — enabling reliable, consistent flow.
Mechanism 2: Absorbing Moisture in Hygroscopic Formulations
In hygroscopic or moist powders, liquid bridges between particles are often the dominant source of cohesion. AEROSIL® Pharma's high specific surface area and hydrophilic silanol-rich surface allow it to absorb this inter-particle moisture, effectively eliminating the capillary forces that cause sticking and clumping. This is particularly valuable when working with humidity-sensitive APIs or in production environments where temperature and humidity control is imperfect.
Mechanism 3: Inhibiting Agglomeration of Fine and Micronised APIs
Crystal micronisation improves dissolution kinetics [CM8.1]and ensures content uniformity in high-potency formulations — but it dramatically increases the specific surface area and agglomeration tendency of the API. Blending AEROSIL® Pharma with micronised APIs before incorporation into the final blend creates a protective coating that inhibits re-agglomeration, preserving the particle size reduction achieved by milling and protecting dissolution performance in the final dosage form.
AEROSIL® Pharma in Direct Compression: Batch and Continuous Processes
Direct compression has become the preferred tableting technology in cost-sensitive environments — especially in generics manufacturing — because it eliminates granulation steps, reduces excipient complexity, and shortens process time. Its success, however, depends entirely on the flow properties of the compression blend. AEROSIL® Pharma has been the industry standard glidant for direct compression since the earliest days of the technology.
Performance in Batch Direct Compression
In conventional batch direct compression, the role of AEROSIL® Pharma is well established across decades of industrial use. At concentrations as low as 0.2 w.-%, measurable improvements in tablet crushing strength and friability are observed. At 0.5 w.-% and above, the improvements become substantial:
- Tablet weight variation is strongly reduced, reflecting the improved and consistent die filling enabled by better powder flow.
- Crushing strength increases, as the silica particles contribute to the mechanical cohesion of the tablet matrix.
- Friability decreases, reducing tablet breakage during handling and packaging.
- Content uniformity improves, directly impacting regulatory compliance and patient safety.
Performance in Continuous Direct Compression
Continuous manufacturing is rapidly evolving from a regulatory aspiration to an operational reality across the pharmaceutical industry. It eliminates batch-to-batch variation, reduces intermediate storage, and aligns with emerging regulatory requirements. Continuous direct compression — the simplest and most widely adopted continuous manufacturing setup — integrates continuous powder feeders, a continuous dry powder mixer, and a tablet press into a single, uninterrupted process stream. In this environment, powder flow is not merely important — it is the controlling variable for the entire system.
AEROSIL® 200 Pharma has been evaluated for use in continuous direct compression through an internal case study conducted in cooperation with Gericke (continuous mixer GCM 500) and L.B. Bohle (QbCon® System). The findings are clear and actionable:
- Feeding at very low rates (down to 100 g/h) is achievable with appropriate loss-in-weight feeding equipment, making micro-dosing of the glidant technically feasible.
- The short residence time of materials in a continuous mixer is sufficient for AEROSIL® 200 Pharma to distribute across host powder particle surfaces and fulfil its flow-enhancing function.
- Consistent powder flow from the mixer to the tableting machine is maintained, reducing powder retention in transfer tubing and facilitating reliable compression chamber filling.
- In the case study formulation, tablets produced with AEROSIL® 200 Pharma showed higher average tablet weight, strongly reduced weight variation, increased crushing strength, and reduced crushing strength variance — all simultaneously.
Case Study Insight (Evonik / Gericke / L.B. Bohle)
Internal case study formulation: 99.0 w.-% Microcrystalline Cellulose (Avicel PH 101) + 0.5 w.-% AEROSIL® 200 Pharma + 0.5 w.-% Magnesium stearate, tested in the QbCon® DG continuous line at L.B. Bohle. Results demonstrated that AEROSIL® 200 Pharma is not merely compatible with continuous direct compression — it is a central excipient for the process, enabling homogeneous and stable tablets across the continuous production run.
The AEROSIL® & AEROPERL® Pharma Portfolio: Choosing the Right Grade for Your Process
While AEROSIL® 200 Pharma is the universal reference standard, Evonik has developed a portfolio of colloidal silicon dioxide grades to address specific formulation and manufacturing challenges. The table below summarizes the range and its primary differentiation points.
Grade | Key Differentiator | Primary Use Case |
|---|---|---|
AEROSIL® 200 Pharma | Universal reference glidant | BET 175–225 m²/g | Full pharmacopoeia compliance | Batch & continuous direct compression; all solid dosage forms |
AEROSIL® 200 VV Pharma | Densified (120 g/L) — half the storage footprint | Same physico-chemical properties | Reduced dust | Space-constrained facilities; coarse or porous host powders; improved dust profile |
AEROSIL® 300 Pharma | Higher BET (270–330 m²/g) | Superior anti-caking | Stronger effect on mechanical tablet stability | Fine powders below 100 µm; thickening of low-polarity oils; enhanced mechanical tablet stability |
AEROSIL® R 972 Pharma | Surface-modified | Hydrophobic | Water repellent | Moisture-sensitive APIs; controlling disintegration time; stabilizing emulsions in semi-solid forms |
AEROPERL® 300 Pharma | Granulated | High density (270 g/L) | Mesoporous carrier | Incorporation of solid & liquid APIs; improving dissolution of poorly soluble actives (BCS II/IV) |
Selection guidance: For most direct compression applications, AEROSIL® 200 Pharma remains the logical first choice. AEROSIL® 200 VV Pharma becomes advantageous when dust management or storage space is a constraint. AEROSIL® 300 Pharma is preferred for finer host powders or when superior mechanical tablet stability is a priority. AEROSIL® R 972 Pharma is the grade of choice when moisture sensitivity drives formulation decisions. And AEROPERL® 300 Pharma is not a glidant but a mesoporous carrier silica for solubility improvement of poorly water soluble APIs. Contact Azelis to discuss which grade best matches your specific formulation constraints.
Processing Guidance: Getting the Most from AEROSIL® Pharma
Mixing Sequence
The order of addition in the blending process significantly affects glidant performance. AEROSIL® Pharma should be incorporated early — either by premixing it with a portion of the excipient mass and sieving the premix (710 µm recommended), or by adding it as the first component to the blender. Early addition ensures that the agglomerates are broken down efficiently and the silica particles distribute evenly across all host powder surfaces before the lubricant phase is added.
Avoiding Lubricant Inactivation
Due to its high specific surface area, AEROSIL® Pharma will absorb stearates and stearic acids if they are introduced simultaneously or before the silica. This adsorption can inactivate both the lubricant and the glidant. Best practice is to add magnesium stearate (or any stearate lubricant) in a separate final mixing step after the silica-containing premix has been fully incorporated.
Mixing Equipment
AEROSIL® Pharma is compatible with all standard pharmaceutical blending equipment: free-fall mixers (V-blenders, double-cone), ploughshare mixers, and continuous powder mixers. The degree of agglomerate break-down is proportional to the shear forces and mixing duration applied — an important consideration when formulating with coarser host powders, which require larger silica particle clusters to remain on their surface for effective flow improvement.
Concentration Optimization
The optimal glidant concentration depends on the host powder particle size, shape, and composition. As a general principle: the finer the host powder, the greater its specific surface area, and the higher the AEROSIL® Pharma concentration required for full coverage. Start at 0.5 w.-% and titrate up or down based on angle-of-repose or shear-cell measurements. For capsule filling and sachet applications, the same principles apply — consistent die/capsule filling is directly dependent on achieving the threshold flow improvement.
Formulator's Rule of Thumb
A starting concentration of 0.5 w.-% AEROSIL® Pharma is recommended for most direct compression formulations. This concentration can be optimized experimentally — increasing for fine powders (greater surface area requires greater silica coverage) or adjusting based on mixing conditions. To maximize efficiency, it is advisable to premix the silica with a portion of the other excipients and pass the premix through a 710 µm sieve before incorporating into the full blend.
Why Source AEROSIL® and AEROPERL® Pharma Through Azelis?
As an Evonik Trusted Partner, Azelis provides more than product supply. Our technical experts in the Pharma & Nutraceuticals sector combine formulation expertise across EMEA with direct access to Evonik's application science — enabling us to support your development team from early formulation screening through technology transfer and commercial scale-up.
- Regulatory documentation support: CoA, SDS, regulatory dossier information for EMEA markets
- Formulation guidance: grade selection, concentration optimization, and mixing protocol design
- Sample provision: for feasibility and pre-formulation studies
- Access to the full AEROSIL® and AEROPERL® Pharma range through a single regional partner
- Multi-country supply capability across the EMEA region with consistent product quality