Moisture sorption and desorption of different commercially available microcrystalline cellulose grades as a function of relative humidity

Abstract

Microcrystalline cellulose (MCC) is extensively used in pharmaceutical formulations due to its exceptional functionality as a diluent, dry binder, disintegrant, and absorbent. Despite being marketed in numerous grades that vary in particle size, source, extraction techniques, and co-processing methods, its basic chemical structure remains consistent across grades, with differences primarily in physical properties. This study investigates moisture sorption and desorption behavior and its effects on solid-state properties of thirteen different MCC grades, including eleven regular and two co-processed varieties, as moisture content significantly influences compaction, tensile strength, and viscoelastic properties. Dynamic vapor sorption analysis was conducted at 25 °C by systematically increasing relative humidity (RH) from 10% to 90% RH in one case and from 10% to 80% RH in another, and then decreasing the RH to 0%. All MCC grades, except one co-processed MCC, exhibited identical moisture sorption- desorption profiles, adsorbing 9.5-10.3% moisture at 80% RH and 12.4-13.5% at 90% RH. Prosolv® 730, a co-processed MCC with silicon dioxide and copovidone, was the only exception showing lower moisture uptake of ~11% and ~8 % at 90 and 80% RH, respectively. Powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) confirmed the semi-crystalline nature of all grades, with increased crystallinity observed at 90% RH, except for Prosolv® 730, which had only minimal change in crystallinity at 90% RH. BET Type II moisture sorption-desorption isotherms were observed with all MCC grades. There were hysteresis loops in the sorption-desorption profiles, where the difference between moisture contents of desorption and sorption profiles was larger when the materials were exposed to the maximum 90% RH versus those exposed to 80% RH, which indicates that moisture is more tightly bound when it is exposed to a higher RH. Despite the reported differences in moisture contents of different marketed MCC grades, this investigation demonstrates that they equilibrate to similar moisture contents when exposed to identical RH conditions. Therefore, protection from humidity would be required to maintain any difference in moisture content among different MCC grades during product processing, stability testing, and storage.

Introduction

Excipients are critically important to the development of drug products, as active pharmaceutical ingredients (API) are rarely taken by or administered to patients alone. Rather, excipients ranging from less than 5% w/w to as high as 99% w/w are used in developing drug products to make the size of individual units convenient for administering to patients, increase accuracy in dosing, improve drug absorption, improve therapeutic effects by modifying drug release rates, improve manufacturability of products, and so forth (1,2). However, despite the importance of excipients to the development of drug products, not as much attention is given in the pharmaceutical field to the physicochemical properties and variability of excipients as is given to different APIs. To fill this gap, we have undertaken systematic investigations of the physicochemical properties of different classes of pharmaceutical excipients as part of our teaching and research program (3–9) Microcrystalline cellulose (MCC) is one of the most versatile and widely used pharmaceutical excipients, serving multiple functions, including as a diluent, dry binder, disintegrant, and absorbent in solid oral dosage forms. Its widespread application can be attributed to its excellent compressibility, superior binding properties, and good flow characteristics. Additionally, it has versatile functionality in various dosage forms as a spheronizing aid for pellet formation and a matrix former for sustained drug release formulations (10). However, like many cellulose-based materials (8), MCC exhibits hygroscopic behavior, making its moisture sorption characteristics a critical quality attribute that demands a thorough understanding for optimal pharmaceutical applications (11). The interaction of MCC with atmospheric moisture is complex and dynamic, significantly influencing its functionality in pharmaceutical formulations. Moisture affects several critical quality attributes of MCC, including flowability, compressibility, and mechanical strength of the resultant tablets (11). Studies have shown that changes in relative humidity (RH) can alter the mechanical properties of MCC-based tablets, with higher moisture generally leading to decreased tablet tensile strength and increased tablet capping tendency. Moisture impacts MCC’s functional properties through several mechanisms.

In particular, moisture can disrupt hydrogen bonding between cellulose chains at a molecular level, affecting the material’s mechanical properties (12). In one recent study, Koumbogle et al. (13) demonstrated that moisture sorption may negatively impact the tableting of MCC as moisture evaporation from the powder bed and accumulation at the punch-tablet interfaces can induce capillary condensation of water between the tablet and the punch during the dwell time, leading to sticking. Based on these considerations, it is essential that the moisture content of the MCC used be controlled for optimal processing and performance of dosage forms.

The chemical structure of MCC is shown in Figure 1. It is generally produced by the acid hydrolysis of cellulose from natural sources, primarily wood and cotton, whereby the chain length of cellulose reduces to a molecular weight in the range of 30,000 to 50,000 (14,15). The hydrolyzed materials are obtained as aqueous slurries, which are then neutralized, washed, and dried. Spray drying is currently the preferred method for drying MCC. Different commercial grades of MCC are produced by controlling their particle size distribution, bulk density, specific surface area, and moisture content during drying, while their fundamental chemical structure remains consistent.

The issue of the moisture content of MCC remains contentious. It is generally recognized that moisture sorption by MCC occurs by hydrogen bonding of water with the hydroxyl groups of MCC. Therefore, different MCC grades should exhibit comparable moisture sorption-desorption patterns, as the interactions between MCC and water are primarily governed by the cellulose chemical structure rather than physical characteristics (14). However, there are different reports in the literature, especially from the manufacturers of MCC, that the commercially available MCC of different grades and sources may differ in their moisture contents. It has been suggested that MCC grades with lower moisture contents should be used for moisture-sensitive drugs. However, no explanation for how moisture contents for different MCC grades vary despite having similar chemical structures, and whether the difference could be retained during the processing and storage of drug products, has been reported in the literature. Therefore, understanding similarities and differences in moisture sorption and desorption patterns across various MCC grades is crucial for optimal excipient selection and process design in pharmaceutical manufacturing. For determining any possible differences in equilibrium moisture contents of different MCC grades, we have conducted a comparative investigation of moisture sorption and desorption as a function of humidity by 13 commercially available grades, where 11 are regular MCC, and two are co-processed MCC. While there are several studies on moisture sorption and desorption by individual MCCs, comparing multiple grades under identical conditions is scarce. Such a comparison is essential for understanding whether the chemical similarity of different MCC grades translates to similar moisture sorption behaviors despite their physical differences.

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Materials

Table 1 lists 13 MCC grades used in the present investigation, along with the names of their manufacturers and some relevant physicochemical properties collected from the literature. Eleven of them are regular MCCs with differing physical properties, and two are co-processed MCCs containing colloidal silicon dioxide only or a combination of colloidal silicon dioxide and copovidone. Microcrystalline cellulose containing silicon dioxide is also commonly known as silicified microcrystalline cellulose or SMCC. There are certain differences in particle sizes of MCC grades in Table 1; however, their bulk densities are around 0.3 and do not differ significantly. According to the manufacturers’ brochures, the moisture contents of different grades could differ. All materials were supplied as gifts by their manufacturers.

Table 1: Microcrystalline cellualose (MCC) used for moisture sorption-desorption analysis*

*All specifications are based on manufacturers’ technical documentation. **IFF announced the sale of its Pharma Solutions business to Roquette Frères S.A., France, in March 2025. ***NMT = Not More Than.

Vishvesh Raje1, Hari P. Kandagatla, Abu T.M. Serajuddin, Moisture sorption and desorption of different commercially available microcrystalline cellulose grades as a function of relative humidity, Received 01 February 2025, Accepted 28th April 2025, IPEC-Americas

Read also our introduction article on Microcrystalline Cellulose here: