(T1030-05-30) Moisture Sorption of Microcrystalline Cellulose

Purpose: Excipients are inert components accompanying active pharmaceutical ingredients in pharmaceutical products. Microcrystalline cellulose (MCC) is extensively used as an excipient in pharmaceutical solid dosage forms due to its exceptional compressibility and compactibility and ability to serve as dry solid binder, diluent, disintegration, and absorbent, MCC has also been considered in multiple novel applications such as 3D printing, carriers for proteins and peptides, etc. Due to the wide applications of MCC, it is marketed for the pharmaceutical industry by different manufacturers in numerous grades. These grades vary based on particle size, source, extraction techniques, co-processing materials, and downstream processing methods. Despite all these variabilities, the primary chemical structure of the MCC is the same for all different grades. The only properties that might show differences are physical properties. The physical properties of commercial MCC have been extensively studied, including variations in different grades for crystallinity, moisture content, surface area, porosity, molecular weight, etc. Literature suggests that MCC moisture content influences compaction, tensile strength, and viscoelastic properties. There are many reports from the manufacturers and suppliers of MCC, as well as literature reports suggesting that the moisture sorption by different grades of MCC, as well as the performance of products developed by using them, may vary. This research primarily focuses on the absorption and desorption patterns of various grades of MCC and the effect of moisture sorption on the solid-state properties of MCC at high moisture levels.

Methods: A systematic study of moisture sorption was conducted using a VTI SA dynamic vapor sorption analyzer. Initially,samples were dried, followed by dynamic vapor sorption analyses at 25°C. Relative humidity (RH) was systematically increased from 10% to 90% at 10% RH intervals to assess moisture sorption. Subsequently, desorption studies were conducted by decreasing humidity from 90% to 10% RH at 10% RH intervals to evaluate materials' desorption behavior. This study considered equilibration at a certain humidity (RH) as percentage weight change below 0.004% within 5 minutes. Each equilibration period was allowed a maximum of 24 hours to reach this threshold. If the weight change remained below 0.004% in 5 minutes, RH progressed to next step. Otherwise, sample remained at given RH for up to 24 hours before transitioning to the next RH level. The MCC grades used were Avicel® (FMC Corporation, Princeton, NJ, USA), Vivapur®, Emocel®; Prosolve® SMCC, PROSOLV^® 730 (PS730) (JRS Pharma, Patterson, NY). Additionally, these samples are subjected to 90% relative humidity (RH) at 25^oC until the weight and observed for changes in solid-state characterizations by DSC and PXRD.

Results: Fig. 1 shows moisture sorption and desorption graphs for various MCCs. Even though every grade had some or the other difference in particle size, moisture content, morphology, or processing method, all the MCCs were superimposable for moisture sorption and desorption. The only exception was seen to be PS 730, which is a co-processed MCC along with silicon dioxide and copovidone. Fig. A(I) shows combined moisture sorption and desorption for MCC to 90% RH value, where a hysteresis loop was observed between the moisture sorption and desorption cycle. This loop indicates that the material retains moisture differently during adsorption and desorption. To avoid the hysteresis loop, samples were only run to 80% RH levels (Fig. B(II)). It reduced the hysteresis loop but could not eliminate it, indicating that some water is tightly bound with MCC. To understand what physical changes it might have made, solid-state analysis was done using DSC and PXRD. Fig. 2(A) shows DSC analysis of all the samples of MCC showing very similar thermal events, first at ~90^oC and another at ~330^oC, the only exception being PS 730. PS 730 showed thermal events at ~80^oC and ~365^oC due to the presence of other co-processed materials. The DSC analysis of PH 102NF was conducted at 90% RH (Fig. 2(B)). Although there is no significant change in the temperatures of the thermal events, the heat flow of the sample at 90% RH was changed more than the sample. Fig. 3(A) shows PXRD for the MCC samples showing major halos at 2θ – 18⁰ and 23⁰. Fig. 3(B) shows changes in the halos of PH102NF after keeping it at 90% RH. Analyzing the area under the curve suggests that there is a 32% increase in the crystallinity of PH102 after keeping it at 90%RH until equilibration.

Conclusion: Even though there are numerous grades available for the MCC in the pharmaceutical market, they are chemically similar. Hence, the ability of all these MCCs to absorb and desorb moisture at various levels of %RH is also similar. The DSC results in the present investigation show that their crystal structures are also similar as all the MCCs studied showed similar melting points. The current study provides a comprehensive investigation into the moisture sorption behaviors of various microcrystalline cellulose (MCC) grades, providing helpful insight for pharmaceutical formulations.

References: Amidon, G.E., Houghton, M.E., 1995. The Effect of Moisture on the Mechanical and Powder Flow Properties of Microcrystalline Cellulose. Pharm. Res. 12, 923–929. https://doi.org/10.1023/A:1016233725612
Chaerunisaa, A.Y., Sriwidodo, S., Abdassah, M., Chaerunisaa, A.Y., Sriwidodo, S., Abdassah, M., 2019. Microcrystalline Cellulose as Pharmaceutical Excipient, in: Pharmaceutical
Formulation Design - Recent Practices. IntechOpen. https://doi.org/10.5772/intechopen.88092
Patel, N.G., Serajuddin, A.T.M., 2022. Moisture sorption by polymeric excipients commonly used in amorphous solid dispersion and its effect on glass transition temperature: I. Polyvinylpyrrolidone and related copolymers. Int. J. Pharm. 616, 121532. https://doi.org/10.1016/j.ijpharm.2022.121532
Sun, C.C., 2008. Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose. Int. J. Pharm. 346, 93–101. https://doi.org/10.1016/j.ijpharm.2007.06.01

Acknowledgements: Thank you, JRS Pharma, IFF for providing samples for MCC


Figure 1 A(I) Moisture absorption and desorption of various MCCs till 90%RH level. A(II) Moisture absorption of MCCs till 90%RH. A(III) Moisture desorption of MCCs from 90%RH till 0% RH.
B(I) Moisture absorption and desorption of various MCCs till 80%RH level. B(II) Moisture absorption of MCCs till 80%RH. B(III) Moisture desorption of MCCs from 80%RH till 0% RH.


Figure 2 (A) DSC thermogram of all the MCC samples from temperature -20oC till 400oC. (B) DSC thermogram of PH102 NF at normal conditions and at 90%RH. The sample with 90%RH does not show a significant change in melting temperatures but shows an increased heat flow rate change, suggesting a slight increase in the crystallinity of the sample.


PXRD for the MCC samples showing major halos at 2θ – 18o and 23o(Left). Fig. 3(B)(Right)shows changes in the halos of PH102NF after keeping it at 90% RH. Analyzing the area under the curve suggests that there is a 32% increase in the crystallinity of PH102 after keeping it at 90%RH until equilibration