Formulation trials with Ibuprofen DC100 for direct compression

Before diving into the formulation trials with Ibuprofen, it is important to understand its global significance. Indeed, Ibuprofen remains a widely used drug for treating fever, pain, and inflammation. Globally, the Ibuprofen market reaches approximately USD 573 million [1] and continues to grow steadily, with a CAGR of 4.8% [2]. The drug can be administered either intravenously or orally; focusing on oral administration, marketed formulations include tablets, capsules, sachets, and stick packs.

Notably, most formulations rely on compaction and compression to create solid dosage forms. However, this process highlights a key challenge with Ibuprofen. Compressing Ibuprofen requires careful handling to achieve adequate compressibility. Consequently, long compression cycles become necessary, as the drug tends to stick over time due to its low melting point. Moreover, applying low compression forces exacerbates these problems, making the process even more demanding.

A simple attempt …

A simple approach can effectively address this issue: granulating Ibuprofen transforms the drug into a novel physical form. Building on this idea, IPC Process-Center GmbH & Co. KG (Dresden, Germany) developed a patented granulation process that does not require additional excipients. As a result, the chemical properties of Ibuprofen remain unchanged, and the new granule, Ibuprofen DC100, can directly replace conventional Ibuprofen in existing formulations while maintaining the registered composition in the outer phase.

Moreover, granules naturally facilitate coating and layering processes with other excipients, which simplifies taste-masking and enables targeted drug release profiles. For a more detailed discussion on how this approach enhances production efficiency, further application notes are available.

Expert’s opinion

Ibuprofen shows stickiness behavior which stresses the compression process in tableting. Take the granulated Ibuprofen DC100 and get rid of that. It will also simplify further coating and layering.

Test the product

Formulation trials with Ibuprofen

Let’s now compare tablet formulations of conventional Ibuprofen with the granulated form, Ibuprofen DC100, focusing specifically on compression runs, which have proven problematic for the conventional drug.

The first formulation uses standard Ibuprofen combined with microcrystalline cellulose (MCC), silica (SiO₂), magnesium stearate (Mg Stearate), and a disintegrant. The exact composition is provided in Table 1. The second formulation replaces standard Ibuprofen with granulated Ibuprofen DC100, while keeping MCC, SiO₂, Mg Stearate, and the disintegrant unchanged. Both formulations are designed to produce tablets weighing approximately 250 mg.

Formulation 1	%
Ibuprofen common formulation including MCC/SiO₂/disintegrant	99.5
Mg stearate	0.5
Sum	100

Table 1: formulation 1 based on conventional Ibuprofen.

Formulation 2	%
Ibuprofen DC100	85.0
+ MCC/SiO₂/disintegrant	14.5
Mg stearate	0.5
Sum	100

Table 2: formulation 2 based on granulated Ibuprofen DC100.

Compression runs

Compression runs were performed on both formulations, and the results reveal clear differences in tablet mass, compression force fluctuation, and crushing strength. Formulation 2 consistently outperformed formulation 1, exhibiting lower compression force fluctuations and slightly lower crushing strength.

Similarly, stickiness to the punch was monitored over time. Conventional Ibuprofen in formulation 1 showed increasing stickiness during a 5.5-hour run, at which point the process had to be stopped. In contrast, granules from Ibuprofen DC100 in formulation 2 displayed no stickiness even after 10 hours.

This striking difference in stickiness has a direct impact on manufacturing efficiency, as reduced sticking minimizes interruptions, shortens production cycles, and ensures more consistent tablet quality.

Parameter	formulation 1	formulation 2
Tablet mass, S_rel (%)	0.9 – 1.4	0.4 – 0.8
Compression force fluctuation	medium	low
Crushing strength, S_rel (%)	10.4	7.4
Sticking to punch	Increasing, process stopped after 5.5 hours	no (after 10 h)

Table 3: Parameters of the compression runs.

Surface properties of Ibuprofen tablets

Examining the tablets’ surfaces reveals notable differences between the two formulations. Formulation 1 exhibits a pronounced roughness, whereas formulation 2, free from stickiness, shows a more homogeneous surface with a clear and even structure. For example, Figure 1 illustrates the rough surface of formulation 1 on the left and the smooth surface of formulation 2 on the right.

Additionally, punches accumulate more material when compressing formulation 1 than formulation 2. This observation indicates a potential quality issue, as the rough surface of formulation 1 could lead to lower production yields due to defective tablets.

Ibuprofen and Ibuprofen DC100 tablet surface

Figure 1: Tablet surface of Ibuprofen formulation 1 (left) and Ibuprofen DC100 formulation 2 (right).

Figure 2: Sticky drug at the punch at the end of the run. Ibuprofen formulation 1 (left) and Ibuprofen DC100 formulation 2 (right).

Summary

Finally, formulation trials using Ibuprofen DC100 for direct compression were conducted.

Although most marketed products still rely on conventional Ibuprofen, examining granulated forms highlights new formulation possibilities and emphasizes the advantages of this approach. In particular, granulated Ibuprofen DC100, as a distinct physical form, enables easier compression during production cycles. This property effectively addresses major challenges, such as stickiness during compression, and helps reduce yield losses. Consequently, Ibuprofen DC100 emerges as a promising alternative for oral formulations.

References

[1] Global Ibuprofen Market Size to Grow at 2-3 Percent CAGR by 2023, Says Beroe Inc

[2] Ibuprofen-API-Markt | 2022 – 27 | Branchenanteil, Größe, Wachstum – Mordor Intelligence