Why Blaine Air Permeability Best Measures Surface Area for VEGHA - Sodium Stearyl Fumarate

I. Abstract

This study by Pehel Specialities addresses the characterisation of specific surface area (SSA) for our Sodium Stearyl Fumarate (SSF), a key lubricant in pharmaceutical manufacturing.

It is recognised that different analytical methods, notably the Blaine air permeability technique (as per Ph. Eur. 2.9.14) and gas adsorption (BET) methods (e.g., Ph. Eur. 2.9.26, USP <846>), yield numerically different SSA values for the same material sample due to the distinct aspects of surface morphology they assess.

This study elucidates why, for the primary function of SSF as a boundary lubricant in standard tableting operations, the "envelope" surface area measured by the Blaine method is considered by Pehel Specialities to be a more direct and critical quality control parameter for ensuring consistent lubricant performance than the "true" total specific surface area determined by BET.

Pehel Specialities' SSF, with a Blaine SSA specification of 1.2 - 2.0 m²/g, is designed for optimal lubrication. While a BET analysis of this same material would yield a significantly higher SSA value (e.g., potentially 3.0 - 5.0 m²/g or more) due to its measurement of total microscopic surface including internal lamellae and particle roughness, it is the consistent "envelope" surface reflected by the Blaine value that governs macroscopic lubricant film formation, die-wall interaction, and ejection performance.

This report details the scientific rationale for prioritising Blaine SSA for routine quality control, its correlation with consistent tablet manufacturing and quality attributes, and clarifies how this approach, in line with Good Manufacturing Practices (GMP), mitigates potential out-of-specification (OOS) interpretations that can arise when specifications are not method-specific.

This ensures that Pehel Specialities consistently delivers SSF with predictable and effective lubricant performance. The complementary role of BET for deeper material characterisation and research and development is also acknowledged.

II. Introduction: Sodium Stearyl Fumarate – The Importance of Functionally Relevant Surface Area in Lubrication

Sodium Stearyl Fumarate (SSF), manufactured by Pehel Specialities, is an established and highly effective excipient in the pharmaceutical industry, primarily functioning as a lubricant in the production of tablets and capsules.[1,2]

Its critical role involves minimising frictional forces between powder particles themselves and between the tablet surface and the die walls and punches during the high-speed compression and ejection phases of manufacturing.[3,4]

This action prevents common tableting issues such as sticking, picking, and capping, and reduces wear on manufacturing equipment.[4,5] SSF is frequently preferred over more traditional lubricants like magnesium stearate due to its comparatively lower hydrophobicity. This characteristic often translates into tangible benefits for the final dosage form, including improved tablet disintegration, faster drug dissolution rates, and reduced sensitivity of the formulation to variations in blending times.[2,6]

The physical characteristics of SSF, particularly its specific surface area (SSA), play a crucial role in its performance. However, the term "specific surface area" can be ambiguous unless the method of measurement is defined, as different methods assess different aspects of a particle's surface.

For a lubricant, the functionally relevant surface area is that which effectively participates in the lubrication mechanisms at macroscopic interfaces (e.g., die walls, granule surfaces).

Pehel Specialities employs the Blaine air permeability method (Ph. Eur. 2.9.14) for routine quality control of our SSF, adhering to a specification of 1.2 - 2.0 m²/g. This value pertains to the "envelope" surface area.

It is understood that if the same batch of SSF were tested by a gas adsorption (BET) method (e.g., Ph. Eur. 2.9.26, USP <846>), a numerically higher SSA value would be obtained because BET measures the "true" total specific surface area, including all microscopic surface roughness, internal pores, and surfaces within particle agglomerates.[7,8]

For SSF, known for its flat, lamellar particles that tend to agglomerate,[9,10] this distinction is significant.

Leading SSF manufacturers, such as JRS Pharma (with their PRUV® brand), provide materials with varying SSA characteristics. Manufacturer-reported data indicates that coarser grades (e.g., PRUV® Coarse Grade) typically exhibit a lower Blaine SSA (in the range of 0.3-1.0 m²/g), while standard grades intended for general tableting (e.g., standard PRUV®) have a moderate Blaine SSA (often in the 1.2-2.0 m²/g range).[11]

Materials processed to achieve very fine particle sizes or high porosity would, by contrast, exhibit significantly higher SSA values if measured by BET, reflecting their increased total surface area. This highlights that the same base material can have different SSA values by different methods, and these different values may be relevant for different grades or characterisation purposes.

This Pehel Specialities study, conducted in adherence with the highest standards of Good Manufacturing Practice (GMP), aims to:

1. Clarify the distinction between "envelope" SSA (Blaine) and "total" SSA (BET).

2. Provide the scientific rationale for why Pehel Specialities considers the Blaine SSA the more critical parameter for routine quality control of standard SSF's lubricant function.

3. Explain how this Blaine-measured envelope surface directly impacts tablet manufacturing (e.g., lubrication efficiency, ejection forces) and final tablet quality (e.g., hardness, friability, disintegration), even though the inherent properties of the material itself are constant.

4. Discuss strategies for clear, method-specific specifications and communication to prevent OOS interpretations when different testing methods are used by different parties.

III. Methodologies for Specific Surface Area Measurement: Assessing Different Aspects of the Same Material

The numerical value obtained for the specific surface area of a given sample of Sodium Stearyl Fumarate is entirely dependent on the analytical technique employed. Two principal pharmacopoeial methods, Blaine air permeability and BET gas adsorption, interrogate the material's surface differently.

A. The Blaine Air Permeability Method (Ph. Eur. 2.9.14): Measuring the "Envelope" Surface Area

The Blaine method determines SSA by measuring the resistance to airflow through a compacted powder bed of defined porosity.[12] The Kozeny-Carman equation, used for calculation, relates this resistance to the surface area of the particles constituting the bed.[13]

Importantly, this method primarily reflects the outer "envelope" surface area of the particles or their agglomerates.[7]

It is the surface accessible to the bulk flow of air and is influenced by particle size, shape, and how the particles pack together. For SSF, composed of flat, lamellar particles which tend to agglomerate,[9,10] the Blaine SSA provides a measure of the surface area presented by these agglomerates and their packing structure.

Why this is relevant for SSF as a lubricant:

The primary die-wall lubrication mechanism involves the formation of a relatively uniform film of lubricant between the tablet edge and the die surface. The Blaine SSA, reflecting the effective surface of SSF agglomerates that will constitute this film and interact macroscopically, is directly pertinent to this function. It also relates to how SSF particles distribute and coat other formulation components during blending.

B. The Gas Adsorption (BET) Method (Ph. Eur. 2.9.26 / USP <846>): Measuring the "True" Total Specific Surface Area

The BET method is based on the physical adsorption of an inert gas (e.g., nitrogen) onto the solid surface at cryogenic temperatures.[8,14] It calculates the amount of gas required to form a monomolecular layer over the entire accessible surface. This includes all external surfaces, plus the area within pores, cracks, surface roughness, and the surfaces of individual primary particles within agglomerates, including the inter-lamellar surfaces of SSF.[7,8] Thus, BET provides a measure of the "true" total specific surface area.

C. Considerations and Potential Interferences in SSA Measurement

While both Blaine air permeability and BET gas adsorption are established pharmacopoeial methods, it is important to acknowledge certain factors that can influence their results and require careful control for accurate and reproducible measurements:

• For Blaine Air Permeability (Ph. Eur. 2.9.14):

  • Powder Bed Packing Consistency: The Blaine method relies on a defined porosity of the compacted powder bed. Variations in the packing procedure, compaction force, or sample preparation can affect the resistance to airflow and thus the calculated SSA. Strict adherence to pharmacopoeial procedures is crucial to minimise such variability.

  • Moisture Content: Moisture adsorbed onto particle surfaces can affect the airflow through the powder bed, potentially leading to inaccurate SSA measurements. Samples should be dried and handled appropriately to ensure consistent moisture levels, as specified in the method.

  • Particle Density: The Kozeny-Carman equation, fundamental to Blaine calculations, assumes a uniform particle density. While generally robust for homogeneous materials like SSF, significant density variations within a sample could introduce minor inaccuracies.

• For Gas Adsorption (BET) (Ph. Eur. 2.9.26/USP <846>):

  • Sample Degassing: Proper and complete degassing of the sample prior to analysis is paramount for BET. Residual adsorbed gases or moisture on the surface can block adsorption sites, leading to an underestimation of the true surface area. Degassing parameters (temperature, time, vacuum) must be carefully optimised and controlled for SSF.

  • Adsorbate Gas Purity: The purity of the inert gas used (e.g., nitrogen) is critical, as contaminants can interfere with the adsorption process.

  • Temperature Control: Maintaining cryogenic temperatures (typically liquid nitrogen) precisely during the adsorption process is essential for accurate measurement of the adsorption isotherm.

  • Selection of Pressure Range: The BET theory assumes a monolayer formation within a specific relative pressure range. Selection of an appropriate pressure range for the adsorption data points is necessary for accurate calculation of the monolayer capacity and thus the SSA.

• Particle Morphology and Agglomeration: For materials like SSF, known for its lamellar particles and tendency to agglomerate, both methods interpret the "surface" differently. The Blaine method measures the effective outer surface of these agglomerates, while BET penetrates into the internal structure and inter-lamellar surfaces. This fundamental difference is not a limitation but rather the reason for the numerical discrepancy, reinforcing the need for method-specific interpretation.

Why this value differs for the same SSF sample:

For an SSF sample that yields a Blaine SSA of 1.5 m²/g, the BET SSA will invariably be higher (e.g., 3.0-5.0 m²/g or more) because it additionally measures the extensive surface area of the lamellae, fine surface features, and inter-particle surfaces within agglomerates that are not fully accounted for by bulk airflow in the Blaine apparatus. Highly micronised or specially processed SSF grades designed to have very fine particle sizes or increased porosity would exhibit even higher BET SSA values.

Table 1: Conceptual Comparison of Blaine and BET for the Same SSF Sample

Feature	Blaine Air Permeability (Ph. Eur. 2.9.14)	Gas Adsorption (BET) (Ph. Eur. 2.9.26 / USP <846>)
Aspect of Surface Measured	"Envelope" surface area of particles/agglomerates [7]	"True" total specific surface area, including all microscopic features [7, 8]
Relevance to SSF Morphology	Reflects how agglomerates of flat, lamellar particles pack and present an outer surface for macroscopic interaction.	Quantifies all accessible lamellar surfaces, roughness, and internal agglomerate surfaces.
Expected Numerical Value for the Same Standard SSF Sample	e.g., 1.2 - 2.0 m²/g	e.g., Significantly > 2.0 m²/g (potentially 3.0 - 5.0 m²/g or more)
Primary Utility for Standard SSF Lubricant QC (Pehel's View)	Critical for assessing consistent macroscopic film-forming and die-wall interaction properties.	Valuable for R&D, deep characterisation, understanding effects of high microporosity or extreme fines.

IV. Correlation of Surface Area with SSF Lubricant Performance and Tablet Characteristics: Prioritising the Functionally Relevant "Envelope" Surface

For Pehel Specialities' Sodium Stearyl Fumarate, the material itself is consistent from batch to batch, and its inherent performance characteristics are therefore also consistent. The Blaine and BET tests simply provide two different numerical descriptions of its surface. Our decision to utilise the Blaine method for routine quality control, targeting an SSA of 1.2 - 2.0 m²/g, is based on the scientific rationale that the "envelope" surface area measured by Blaine is more directly correlated with SSF's primary functional performance as a boundary lubricant in standard pharmaceutical tableting operations.

Table 2: Conceptual Comparison of Blaine and BET for different grades

SSF Grade (Hypothetical)	Expected Blaine SSA (m2/g)	Expected BET SSA (m2/g)
Coarse Grade SSF	0.3−1.0 (eg, 0.6)	1.0−2.5 (eg., 1.8)
Standard Grade SSF (Pehel's)	1.2−2.0 (eg., 1.5)	3.0−5.0 (eg, 4.0)
Highly Micronized SSF	2.5−4.0 (eg., 3.0)	7.0−15.0+ (eg, 10.0)

Note: These values are conceptual and illustrative, reflecting typical industry trends for different grades. Actual values would depend on specific manufacturing processes and material characteristics."

Why the "Envelope" Surface Area (Blaine SSA) is Critical for SSF's Lubricant Function:

1. Effective Die-Wall Lubrication: The most critical role of SSF is to form a coherent, low-shear strength film between the compacted tablet edge and the die wall, thereby minimising ejection forces.[3,4] The Blaine SSA reflects the surface characteristics of SSF particles and their agglomerates as they pack and orient at this interface. A consistent Blaine SSA ensures that a predictable and effective lubricating film is formed by the bulk material, leading to smooth tablet ejection. The internal surfaces of SSF's lamellar structure or fine surface roughness (measured by BET) are less directly involved in this primary macroscopic film formation at the die wall.

2. Uniform Blending and Particle Coating: During blending, SSF must distribute uniformly to coat the surfaces of the API and other excipients. The Blaine SSA, by characterising the "envelope" or effective interacting surface of the SSF agglomerates, provides an indication of its bulk distributive properties. This ensures adequate coverage of host particles, preventing direct contact and reducing inter-particulate friction during compaction.

3. Controlling Effective Lubricant Concentration at Interfaces: The Blaine value represents the surface area that is effectively presented by the SSF particles to other surfaces (granules, die walls, punches) during the dynamic process of tableting. It's this effectively interacting surface that dictates lubrication.

4. Optimising Lubrication Without Over-Lubrication: While a larger surface area might intuitively seem better, "more" is not always optimal for lubricants. Excessive lubrication can significantly weaken inter-particulate bonding, leading to soft tablets with poor mechanical strength (over-lubrication).[15] The Blaine SSA helps control the amount of effectively interacting surface area. For standard SSF grades, it prevents the selection or production of material that might have an excessively high total surface area (as BET would reveal for highly micronised or extremely porous variants) which could lead to over-lubrication. General pharmaceutical formulation principles indicate that lubricants with excessively high surface areas (e.g., due to extreme micronisation) can lead to decreased tablet tensile strength.[15,16] By focusing on a controlled Blaine SSA, Pehel Specialities ensures sufficient lubrication without compromising tablet integrity.

5. Practical and Reliable Quality Control: The Blaine method is a well-established, relatively simple, and rapid technique suitable for routine QC.[13] By ensuring batch-to-batch consistency of the functionally critical "envelope" surface area, Pehel Specialities assures consistent lubricant performance of its SSF.

Impact of the Blaine-Measured "Envelope" Surface Area on Tablet Properties:

The same batch of Pehel Specialities' SSF, consistently meeting our Blaine SSA specification of 1.2 - 2.0 m²/g, will exhibit predictable performance. If this same batch were also tested by BET, it would give a higher SSA value, but this does not change its inherent performance characteristics; it simply provides a different descriptor. The following impacts are discussed based on the Blaine SSA being the controlled variable:

• Lubrication Efficiency and Ejection Forces:

  
  

  A Pehel Specialities SSF batch meeting the 1.2-2.0 m²/g Blaine SSA specification will provide optimal surface coverage for die-wall film formation and inter-particulate lubrication. This leads to consistent and low ejection forces, minimising stress on tablets and tooling. This performance is comparable to other standard SSF grades with similar Blaine SSA values (e.g., manufacturer-reported data for standard grades of JRS PRUV® are in this range). If a batch had a Blaine SSA significantly below this range (e.g., akin to manufacturer-reported data for PRUV® Coarse Grade, ~0.6 m²/g), it would imply a coarser effective particle envelope, potentially leading to less efficient surface coverage and requiring higher usage levels to achieve the same lubrication.

• Tablet Hardness and Friability: Achieving target tablet hardness and low friability depends on a delicate balance: sufficient lubrication to enable tablet formation and ejection, but not so much as to significantly impair inter-particulate bonding. Pehel Specialities' SSF, with its controlled Blaine SSA of 1.2-2.0 m²/g, is designed to strike this balance.

• An SSF with a Blaine SSA too low might lead to poor distribution and insufficient lubrication, resulting in high frictional stresses, potentially leading to capping, lamination, or sticking, and inconsistent tablet strength.

• An SSF with a Blaine SSA that is too high (implying an extremely fine "envelope" surface even before considering the total BET surface) could begin to exhibit over-lubrication tendencies itself, leading to weaker tablets. The problem is exacerbated if decisions are based on an uncontrolled, very high BET SSA (as would be seen in highly micronised SSF [15,16]). By controlling the Blaine SSA, we manage the effective interacting surface to ensure robust tablet bonding.

• Tablet Disintegration and Drug Dissolution:

  
  

  SSF's favourable hydrophilic character promotes faster disintegration and dissolution compared to lubricants like magnesium stearate.[2,6]

• The Blaine SSA reflects the external surface of SSF agglomerates initially exposed to the dissolution medium. Consistent Blaine values contribute to predictable initial wetting behaviour and de-agglomeration of the lubricant within the tablet matrix.

• Once the tablet disintegrates and SSF particles are dispersed, the "true" total surface area (which BET would quantify) becomes available for interaction with the dissolution medium. SSF's lamellar structure means this total surface is extensive.[9,10] However, the initial performance and consistency of disintegration are strongly influenced by how the lubricant behaves as a bulk component, a characteristic better controlled by the Blaine SSA for standard grades.

While BET analysis provides valuable data for R&D, for understanding highly specialised grades (e.g., micronised), or for deep material characterisation, Pehel Specialities maintains that for routine quality control of standard SSF intended for general lubrication purposes, the Blaine SSA is the more direct and functionally relevant parameter. Our focus on the 1.2-2.0 m²/g Blaine SSA ensures our SSF consistently delivers the expected lubrication performance and contributes positively to final tablet quality, batch after batch.

V. Pehel Specialities' Approach to Ensuring Product Quality and Mitigating Method-Related Discrepancies: A Risk-Based Framework

Pehel Specialities is dedicated to supplying Sodium Stearyl Fumarate (SSF) that consistently meets the highest pharmaceutical quality standards. Our approach to specific surface area (SSA) characterisation is rooted in a scientific understanding of SSF's function as a lubricant and is rigorously aligned with Good Manufacturing Practices (GMP). We prioritize the analytical method that best reflects the functionally critical attributes of our SSF, thereby implementing a robust risk mitigation strategy for pharmaceutical manufacturing.

A. Prioritising the Blaine Method for Functionally Relevant SSA Control: A Risk Mitigation Strategy

Pehel Specialities utilises the Blaine air permeability method (Ph. Eur. 2.9.14) for routine quality control and release of our SSF, with a specification of 1.2−2.0 m2/g. This decision is a deliberate risk mitigation strategy based on our assessment that the "envelope" surface area measured by Blaine is the most direct and relevant indicator of SSF's bulk performance as a lubricant in standard tableting operations. Controlling this specific parameter directly minimises the risk of:

• Inconsistent Die-Wall Lubrication: Ensuring consistent film formation on die walls, thereby reducing the risk of high ejection forces, tablet sticking, and tooling wear.

• Poor Blend Uniformity: Promoting uniform distribution during blending, which prevents localized friction and potential tablet defects like capping or lamination.

• Over-lubrication Induced Tablet Weakness: By controlling the effectively interacting surface area, we prevent the selection or production of material that could lead to compromised tablet hardness and increased friability due to excessive lubrication.

Our historical data confirm our ability to consistently manufacture SSF within this target Blaine SSA range, providing a reliable and predictable lubricant. This approach aligns with how standard lubricant grades are often characterised for QC, where Blaine SSA reflects effective surface properties.

B. Understanding the Complementary Role of BET Characterisation and Associated Risks

We recognise that the BET gas adsorption method (e.g., Ph. Eur. 2.9.26, USP <846>) provides a measure of the "true" total specific surface area, which for the same sample of our SSF, will yield a numerically higher value (e.g., anticipated 3.0−5.0 m2/g or more) than the Blaine method. This is due to BET's ability to account for SSF's lamellar particle structure, surface roughness, and inter-particle surfaces within agglomerates. While invaluable for fundamental material science, R&D, and characterising highly specialised grades, relying solely on BET for routine QC of standard SSF's lubricant function presents inherent risks:

• Risk of Misleading OOS Results: A standard SSF batch perfectly suitable for lubrication could appear 'out-of-specification' if a BET-based specification were applied without functional justification, leading to unnecessary investigations and potential batch rejection.

• Irrelevant Control Parameter: The vast internal surface area measured by BET may not directly influence the macroscopic lubrication process in standard tableting, making it a less efficient primary QC parameter for this specific application.

• Complexity and Cost: BET analysis is generally more complex, time-consuming, and expensive than Blaine, making it less practical for high-throughput routine QC unless functionally justified.

Pehel Specialities utilises BET analysis for:

• In-depth material characterisation during product development and research.

• Understanding the properties of specialised grades (e.g., if developing a micronised version or material with enhanced porosity) where the total surface area may be more functionally relevant.

• Investigating any unexpected performance correlations where total surface interaction might be implicated.

However, for routine QC of standard grade SSF for its lubricant function, we maintain that Blaine SSA is the primary control parameter, effectively mitigating the risks outlined above.

C. Bridging Understanding Between Methods: Mitigating Communication Risks

While we do not aim to establish a direct numerical conversion or "correction factor" between Blaine and BET results (as they measure fundamentally different aspects of surface), Pehel Specialities invests in understanding the typical relationship between Blaine and BET values for our SSF. This involves periodically testing batches by both methods to confirm that our material, which meets the Blaine specification, also exhibits a BET SSA consistent with a high-quality standard SSF grade possessing a well-defined particle morphology. This understanding aids in technical discussions and ensures a comprehensive material profile, mitigating communication risks with customers who may utilize different analytical methods.

D. Clear Communication, Specification Strategy, and GMP Compliance: Ensuring Supply Chain Integrity

To proactively prevent OOS interpretations and ensure robust supply chain integrity arising from the use of different SSA methodologies, Pehel Specialities adheres to the following GMP principles:

• Method-Specific Specifications: Our release specification of 1.2−2.0 m2/g is unequivocally tied to the Blaine air permeability method (Ph. Eur. 2.9.14). This clarity is paramount to avoid ambiguity and is explicitly stated on our Certificates of Analysis and in all product documentation.

• Transparent Information: We proactively communicate with users about the SSA measurement method used for our SSF and explain why the Blaine SSA is critical for its intended lubricant function. We also provide information on the expected differences if other methods like BET are used, thereby reducing the risk of misinterpretation.

• Adherence to ICH Guidelines: Our specification setting aligns with ICH Q6A principles, ensuring that acceptance criteria are justified and linked to product performance and manufacturing consistency. Our analytical methods are validated or verified according to ICH Q2(R1) and relevant pharmacopoeial chapters (e.g., USP <1225>), providing documented assurance of method suitability.

• Quality Technical Agreements (QTAs): We strongly advocate for and work with customers to establish QTAs. These agreements clearly define, among other parameters, the analytical methods to be used for testing SSF (including SSA), the corresponding specifications, and procedures for addressing any discrepancies. This proactive approach minimizes the risk of disputes and ensures mutual understanding and alignment throughout the pharmaceutical supply chain.

By focusing our routine QC on the functionally relevant Blaine SSA, while utilising BET for deeper characterisation and transparently communicating our approach, Pehel Specialities ensures that our Sodium Stearyl Fumarate consistently delivers optimal performance as a pharmaceutical lubricant, thereby contributing to the consistent quality and safety of finished drug products.

VI. Conclusion

This Pehel Specialities study has systematically addressed the critical issue of specific surface area (SSA) measurement for Sodium Stearyl Fumarate (SSF) and its implications for pharmaceutical applications. Our core finding is that while different analytical methods like Blaine air permeability and BET gas adsorption will yield numerically different SSA values for the exact same sample of SSF, it is the "envelope" surface area, as measured by the Blaine method (Ph. Eur. 2.9.14), that Pehel Specialities considers most directly relevant for controlling the functional performance of our standard grade SSF as a lubricant.

Pehel Specialities' commitment to a Blaine SSA specification of 1.2 - 2.0 m²/g is founded on the scientific understanding that this parameter effectively characterises the macroscopic surface properties governing SSF's ability to form consistent lubricating films at die walls, distribute uniformly during blending, and reduce ejection forces without causing detrimental over-lubrication. This ensures predictable and reliable performance in tablet manufacturing. The inherent properties of SSF, including its lamellar structure and tendency to agglomerate,[9,10] mean that its "true" total specific surface area, as measured by BET (e.g., Ph. Eur. 2.9.26, USP <846>), will be substantially higher (potentially 3.0 - 5.0 m²/g or more for the same material). While BET SSA is invaluable for fundamental material science, R&D, and characterising specialised grades (e.g., highly micronised SSF, where very high BET SSA can correlate with over-lubrication [15,16]), it is not the primary parameter for routine QC of standard SSF's bulk lubricant function.

The potential for out-of-specification (OOS) interpretations when different parties use different SSA methods for the same material is significant. Pehel Specialities mitigates this risk through a GMP-compliant strategy: clearly defining our release specification as Blaine-specific, transparently communicating the scientific rationale for our method choice, and utilising Quality Technical Agreements to align with customer expectations. Our approach is consistent with ICH guidelines on method validation (ICH Q2(R1) [20]) and specification setting (ICH Q6A [18,19]).

Ultimately, Pehel Specialities ensures that each batch of our SSF, meeting our Blaine SSA specification, possesses the consistent material attributes necessary for optimal performance as a pharmaceutical lubricant.

References

[1] Hölzer, A. W., & Sjögren, J. (1979). Evaluation of sodium stearyl fumarate as a tablet lubricant. International Journal of Pharmaceutics, 2(3), 145-153.

[2] Wang, J., Wen, H., & Desai, D. (2010). Lubrication in tablet formulations. European Journal of Pharmaceutics and Biopharmaceutics, 75(1), 1-15.

[3] Moreton, R. C. (2009). Tablet lubricants. In L. Augsburger & S. W. Hoag (Eds.), Pharmaceutical Dosage Forms: Tablets (Vol. 2, 3rd ed., pp. 225-261). Informa Healthcare.

[4] Schiller, M., Glinecke, R., & Lammens, R. (2007). Characterisation of lubricants using a compaction simulator. European Journal of Pharmaceutics and Biopharmaceutics, 65(2), 226-236.

[5] Gilding, D. K., & Webb, P. (1980). Sodium stearyl fumarate as a tablet lubricant. Manufacturing Chemist, 51(11), 34-37.

[6] Shah, N. H., Stiel, D., Weiss, M., & Infeld, M. H. (1986). Evaluation of two new tablet lubricants—sodium stearyl fumarate and glyceryl behenate. Measurement of physical parameters (compaction, flowability, and particle size) of the lubricants and their effects on the dissolution of a model drug from a tablet. Drug Development and Industrial Pharmacy, 12(8-9), 1329-1346.

[7] Lowell, S., Shields, J. E., Thomas, M. A., & Thommes, M. (2004). Characterization of Porous Solids and Powders: Surface Area, Pore Size and Density. Springer.

[8] Brunauer, S., Emmett, P. H., & Teller, E. (1938). Adsorption of Gases in Multimolecular Layers. Journal of the American Chemical Society, 60(2), 309-319.

[9] Hussain, M. S. H., York, P., & Timmins, P. (1992). Physico-chemical and crystallographic characterization of sodium stearyl fumarate. International Journal of Pharmaceutics, 80(1-3), 65-73.

[10] Müller, F., & Schaefer, T. (1991). Characterization of sodium stearyl fumarate samples with respect to their lubricating properties in direct tableting. Drug Development and Industrial Pharmacy, 17(10), 1329-1348.

[11] (Statement based on common industry knowledge of lubricant grades and manufacturer-reported data for products such as JRS Pharma's PRUV® range; specific CoAs or internal manufacturer data are not citable as research papers but reflect industry practice for grade differentiation by SSA.)

[12] European Pharmacopoeia (Ph. Eur.), 11th Edition. (2023). 2.9.14. Specific surface area by air permeability. Council of Europe, EDQM.

[13] Kozeny, J. (1927). Über kapillare Leitung des Wassers im Boden. Sitzungsber Akad. Wiss. Wien, 136(2a), 271-306.

[14] European Pharmacopoeia (Ph. Eur.), 11th Edition. (2023). 2.9.26. Specific surface area by gas adsorption. Council of Europe, EDQM. (See also: United States Pharmacopeia and National Formulary (USP-NF). General Chapter <846> Specific Surface Area.)

[15] Kikuta, J. I., & Kitamori, N. (1994). Effect of lubricant mixing time on tablet properties. Drug development and industrial pharmacy, 20(3), 319-333. (Discusses over-lubrication phenomena).

[16] Roberts, R. J., & Rowe, R. C. (1987). The effect of lubrication on the compaction of a range of direct compression excipients. International journal of pharmaceutics, 37(1-2), 167-171. (General principles of lubricant effects on tablet strength).

[17] Strickland, W. A., Jr., & Sugita, E. T. (1970). Study of the mechanism of action of tablet lubricants I: Effect of concentration and mixing time of magnesium stearate and talc on the specific surface area of sulfadiazine granulations. Journal of Pharmaceutical Sciences, 59(5), 657-660. (While about MgSt/Talc, discusses SSA changes and lubricant mechanisms which have conceptual relevance).

[18] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). (1999). ICH Harmonised Tripartite Guideline Q6A: Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances.

[19] FDA, Center for Drug Evaluation and Research (CDER). (2018). Guidance for Industry: Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances — Questions and Answers.

[20] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). (1995/2005). ICH Harmonised Tripartite Guideline Q2(R1): Validation of Analytical Procedures: Text and Methodology.

[21] United States Pharmacopeia and National Formulary (USP-NF). General Chapter <1225> Validation of Compendial Procedures.

[22] FDA, Center for Drug Evaluation and Research (CDER). (2016). Guidance for Industry: Contract Manufacturing Arrangements for Drugs: Quality Agreements.