For the proper handling of powdered active pharmaceutical ingredients (APIs) and excipients, excellent flowability is of paramount importance. Powders that tend to agglomerate or exhibit poor flowability pose significant challenges in transportation and accurate dosing. The achievement of homogeneous blending between APIs and other formulation components is compromised in the presence of caking, wall sticking, or electrostatic charging issues.

The incorporation of a small dosage (0.2-2%) of SYLOID® FP Silica can effectively enhance the flow properties of pharmaceutical formulations. The precisely engineered porous structure of SYLOID® FP Silica enables unique intermolecular interactions, charge regulation, and capillary force generation, thereby imparting superior free-flow characteristics, glidant performance, and anti-caking effects to the formulations.

SYLOID® 244FP, AL-1FP (for EU market), and 63FP (for US market) are synthetic amorphous silica excipients. Manufactured under strictly controlled conditions, they ensure exceptional chemical purity. W. R. Grace & Co.-Conn. is the exclusive manufacturer of SYLOID® FP Silica, providing full supply chain traceability and custody. All SYLOID® FP Silica grades are certified to comply with the latest monograph requirements for Silicon Dioxide in the United States Pharmacopeia - National Formulary (USP-NF), Hydrated Silicon Dioxide in the Japanese Pharmaceutical Excipients (JPE), and Colloidal Hydrated Silica in the European Pharmacopoeia (EP).

Powder flow behavior is influenced by a combination of factors, including the intrinsic characteristics of raw materials, interparticle interactions, surface properties of contact materials, and various environmental conditions. The most common flow-related challenges in pharmaceutical manufacturing include caking, wall sticking, and electrostatic charging. This relationship is illustrated in the graph below, which correlates the force required to initiate and sustain powder flow with the powder's movement velocity.

Free Flowing Zone Caking Zone

Figure 1 A higher initiation force is required to set stationary powder in motion, and this force decreases as the powder maintains flow. Caking typically occurs at the initial stage characterized by high force and low flow velocity, while free flowability is progressively improved with the increase of flow speed.

Hygroscopic pharmaceutical products, such as plant-derived APIs, anti-infective drugs, lyophilized formulations, probiotics, and many others, tend to adsorb atmospheric moisture based on the ambient relative humidity (RH), leading to particle agglomeration and stickiness. Caking can also occur when powders are not fully dried, or when moisture migrates to the particle surface after the drying step in wet granulation processes.

SYLOID® FP Silica is a highly porous, micronized silica powder. When added to formulations, its high porosity enables the adsorption of a substantial amount of moisture, keeping the product dry and enhancing formulation stability. This unique property is clearly demonstrated in Figure 2, which presents the moisture adsorption capacity of various flow-enhancing additives under different RH conditions. The optimal moisture-controlling additive can be selected according to the specific ambient RH of the manufacturing and storage environment. Maintaining low moisture levels in formulations prevents moisture migration to APIs, thus preserving the chemical and physical stability of the final product.

Figure 2 The higher specific surface area and internal porosity of SYLOID® FP Silica confer superior moisture adsorption capacity compared to other silicon dioxide excipients.

Direct compression offers numerous advantages over other tablet manufacturing processes, including enhanced formulation stability, lower production costs, and simplified operational procedures. However, the successful implementation of direct compression requires API-excipient blends with both excellent flowability and compressibility, which is a well-recognized challenge in formulation development. The two-step glidant mixing process provides an effective solution to prepare such ideal blends, achieving optimal flow and compression properties for direct compression while maintaining the homogeneity and stability of the formulation throughout the manufacturing process.

SYLOID® FP Silica excipients can be utilized in both stages of the two-step glidant mixing process. In the API pre-mixing stage, SYLOID® AL-1FP (EU) or SYLOID® 63FP (US) is recommended to maximize API stability. Its ultra-high specific surface area forms hydrogen bonds with moisture molecules, converting free moisture into bound water with high stability. In the secondary blending stage, SYLOID® 244FP is employed to prevent caking and particle segregation during mixing and subsequent processing. SYLOID® 244FP adsorbs an optimal amount of moisture to achieve free-flowing powder blends, while its internal porosity retains a sufficient quantity of physically adsorbed water to provide the plasticizing and binding properties essential for tablet processing.

Particle shape and size exert a profound influence on powder free flowability, segregation tendency, and blend uniformity. In general, spherical particles exhibit better flow properties than non-spherical ones, and larger particles outperform smaller ones in flowability. Additionally, a more homogeneous particle size distribution contributes to improved flow behavior. SYLOID® FP Silica features a narrow, well-controlled particle size distribution, which is critical for maintaining blend uniformity in direct compression processes.

The micronization of SYLOID® FP Silica particles effectively prevents segregation and significantly improves the flow properties of blends containing micronized APIs or other micronized excipients. Such enhanced flowability not only facilitates general pharmaceutical processing but also brings particular benefits to co-processing and pre-mixing operations.

Elevated temperatures have a detrimental effect on powder free flowability and may induce severe caking. This effect is particularly pronounced in oil and lipid-containing formulations, where even a slight temperature increase can lead to significant agglomeration. Temperature fluctuations can alter the moisture adsorption capacity of materials and cause condensation on cold surfaces, both of which contribute to caking formation.

Prolonged storage of packaged pharmaceutical products under pressure, especially when combined with high moisture levels, can result in caking due to particle compaction and agglomeration.

Binders, hygroscopic materials, and oil-containing formulations are inherently prone to caking. Lyophilized and freeze-dried products (e.g., probiotics, peptides) frequently encounter electrostatic charging issues during processing. For electrostatic problems, the porous structure and capillary forces of SYLOID® 244FP enable efficient charge neutralization, reducing electrostatic behavior and minimizing the adhesion of powder particles to processing equipment. For formulations with a tendency to stick to processing surfaces, the addition of finely milled silica powder such as SYLOID® FP Silica forms a protective coating on the surface of other ingredients, reducing adhesion and effectively preventing caking and wall sticking.

*For more detailed information on the two-step glidant mixing process, please request our dedicated application note.

Washburn’s Equation can be used to quantitatively predict the wettability of pharmaceutical powders. Its potential applications in formulation development include the calculation of drug release kinetics, optimization of formulation composition, and determination of adhesion tendencies during manufacturing processes.

Washburn's Equation: $$L^2=(C \times r) \times \gamma \times cos\Phi / 2 \times \eta$$

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For more information about SYLOID® FP Silica, please visit: SYLOIDFP.com

The information contained herein is based on W. R. Grace & Co.-Conn.'s internal testing and practical experience, and is provided for your consideration and verification. Due to the significant variation in operating conditions which are beyond our control, W. R. Grace & Co.-Conn. disclaims all warranties, express or implied, regarding the results obtained from the use of our products. W. R. Grace & Co.-Conn. and its subsidiaries shall not be liable for any damage or injury arising from the improper installation or use of our products. Grace reserves the right to modify product prices and/or specifications without prior notice.

GRACE® and SYLOID® are registered trademarks of W. R. Grace & Co.-Conn. in the United States and/or other countries. TALENT TECHNOLOGY TRUST™ is a trademark of W. R. Grace & Co.-Conn. This trademark list is compiled based on published information available at the time of this brochure's publication and may not reflect the current trademark ownership or status accurately.

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