Microcrystalline Cellulose in Solid Dosage Forms: A Guide to Quality and Sourcing

In 1955, microcrystalline cellulose (MCC) was first discovered as a potential ingredient for use in solid pharmaceutical dosage forms. A decade later, its first commercial product was made available to the pharmaceutical industry under the brand name Avicel® PH. Fast-forward to today and MCC is one of the most popular pharmaceutical excipients used in tablet manufacturing and is manufactured globally by numerous suppliers. 

In this article, we will give you a complete overview of microcrystalline cellulose, from its description to its production process, application in the pharmaceutical industry, and tips for sourcing high-quality MCC for your organization. 

So, without further ado, let’s dive right into the article! 

What is Microcrystalline Cellulose (MCC)?

Microcrystalline Cellulose (MCC) is a refined form of cellulose, the most abundant natural polymer on Earth. It is derived from alpha cellulose, which is sourced from plant materials such as wood pulp or purified cotton linters. MCC is produced as a highly purified, partially depolymerized cellulose by controlled acid hydrolysis. This process removes the amorphous regions of cellulose, resulting in a crystalline structure with unique physicochemical properties, and is widely used in pharmaceuticals. 

Chemical Structure

Cellulose is a linear polymer composed of D-glucose units linked by β(1→4)-glycosidic bonds. In its natural state, cellulose chains form microfibrils, which are aggregates of molecules held together by hydrogen bonds, resulting in a semi-crystalline structure comprising crystalline and amorphous regions. The crystalline regions confer rigidity and strength, while the amorphous regions are more flexible. 

During the production of MCC, acid hydrolysis selectively removes these amorphous regions, yielding shorter, crystalline segments. The resulting MCC consists of crystalline cellulose fragments, which contribute to its desirable properties such as high compressibility and binding capacity. 

Production Process

Microcrystalline Cellulose is produced through a series of processes briefly discussed below: 

Sourcing of Cellulose

In the first step, the primary raw material (cellulose) is sourced from high-quality sources like wood pulp and purified cotton linters. However, wood pulp is the preferred raw material due to its high cellulose content, which ensures that the final MCC product meets the required specifications for pharmaceutical applications.

Pulping Process

In the next step, the raw plant material undergoes a process called pulping to extract cellulose from other components like lignin and hemicellulose. Pulping is performed through chemical treatments such as the Kraft process, which uses a mixture of sodium hydroxide and sodium sulfide to break down lignin and release cellulose fibers. Alternative pulping processes, such as sulfite and organosolv methods, can also be used depending on the desired properties of the final cellulose product.

Alkali Treatment

Once the cellulose fibers are extracted, they are then treated with an alkaline solution at high temperatures. Alkali treatment is used to remove residual hemicelluloses and purify the cellulose even further. 

Acid Hydrolysis

The purified cellulose is subjected to acid hydrolysis using mineral acids like hydrochloric acid. Acid hydrolysis is a critical step because it selectively hydrolyzes the amorphous regions of the cellulose fibers, leaving behind only the crystalline regions. The controlled nature of acid hydrolysis allows manufacturers to optimize the degree of depolymerization, influencing the final properties of the MCC, such as its crystallinity and particle size distribution.

Washing and Filtration

After hydrolysis, the crystalline cellulose fibers are thoroughly washed to remove soluble by-products and residual acids. The insoluble crystalline cellulose is then separated by filtration. 

Drying and Milling

In the final step, the filtered cellulose is dried to produce a fine powder. After drying, a final process called Milling is employed to achieve the desired particle size distribution, producing the final product – MCC.  

MCC as an Excipient in Solid Dosage Forms

Microcrystalline cellulose is a versatile and most commonly used excipient in pharmaceutical solid dosage forms. Its versatility stems from its unique physicochemical properties that allow it to perform various roles. For example,

Compressibility and Compactibility

MCC exhibits excellent compressibility, making it ideal for direct compression processes in tablet manufacturing. Its ability to form hard compacts under pressure imparts the tablets with the much-needed mechanical strength. 

Inertness and Stability

MCC is chemically inert, so it does not react with active pharmaceutical ingredients (APIs) or other excipients, which makes it compatible with a wide range of APIs. The stability of MCC under various environmental conditions, such as humidity and temperature, also makes it a reliable excipient for long-term storage and transport.

MCC as a Multipurpose Excipient

What makes microcrystalline cellulose unique is its ability to serve different functions in tablet formulation. Thus, it’s used as a binder, diluent(filler), disintegrant, lubricant, and glidant. 

As a Binder

When used as a binder, MCC enhances the cohesion and mechanical strength of tablets. Its plastic deformation under compression contributes to the formation of strong interparticle bonds, which imparts high tensile strength to tablets. The use of MCC as a binder is particularly advantageous when formulating tablets with poorly compressible APIs, where higher binding capacity is required.

As a Diluent

For tablets containing low-dose active ingredients, MCC is used as a filler/diluent to add bulk, facilitating the production of tablets of appropriate size and weight for patient handling. 

As a Disintegrant

Disintegrants cause tablet breakdown to release API. MCC serves this purpose so that upon ingestion, tablets disintegrate readily inside the gut. The disintegrant property of MCC arises from its capillary action and swelling properties that facilitate the rapid uptake of gastrointestinal fluids, leading to tablet disintegration. In fact, recent innovations in MCC formulations have focused on optimizing these disintegration properties for fast-release formulations that enhance bioavailability.

Lubricant and Glidant

MCC improves powder flow properties during manufacturing, acting as a glidant. While it is not a lubricant in the traditional sense, its ability to reduce friction between particles enhances flowability, which is integral for uniform die filling and weight consistency in tablet production. 

Quality Considerations for MCC

When sourcing MCC, the first thing to consider is its quality, which is assessed by reviewing its physicochemical properties, compliance with regulatory standards, and functional performance testing. 

Physicochemical Properties

● The particle size and distribution of MCC impact its flow properties and compressibility. Uniform particle size ensures consistent flow during processing, leading to tablets with uniform weight and strength. On the other side, variations in particle size can cause issues like segregation and inconsistent tablet hardness. 

● MCC is hygroscopic, meaning it readily absorbs moisture from the environment. Controlling its moisture content is essential, as excessive moisture can lead to microbial growth and compromise tablet integrity, while insufficient moisture may affect compressibility and tablet formation. 

● The degree of polymerization and crystallinity of MCC affects its mechanical properties, such as hardness and tensile strength. 

Regulatory Standards

● Compliance with regulatory standards like those outlined in the USP and EP provides assurance that the MCC used is of pharmaceutical grade, and adheres to established purity and performance criteria. In addition, manufacturers should also ensure that the MCC conforms to the International Pharmacopoeia and other regional guidelines, depending on their market.

Functional Performance Testing

● Good flow properties are vital for uniform die-filling during tablet compression. Aspects like Angle of Repose and Bulk Density are used to provide insights into the flowability of MCC, ensuring consistent tablet weight and content uniformity. 

● Tablet Hardness and Friability Tests are yet another notable functional performance testing parameters used to evaluate compressibility and compactibility. These tests help evaluate whether the tablets can withstand mechanical stresses during packaging, transportation, and handling without breaking or chipping. 

● Disintegration and dissolution tests confirm that tablets release the active pharmaceutical ingredient (API) within the prescribed. 

Sourcing Tips for High-Quality MCC

As a pharmaceutical manufacturer, there are three important aspects you should consider when sourcing high-quality microcrystalline cellulose. These include: selecting reputable suppliers, evaluating supply chain transparency, and cost considerations.

Selecting Reputable Suppliers

When evaluating suppliers for Microcrystalline Cellulose (MCC), it is essential to choose those who adhere to Good Manufacturing Practices (GMP) and hold relevant quality certifications, assuring that the MCC meets stringent quality standards. Suppliers should also have a proven track record of reliability, with quality assurance systems in place to address potential quality issues effectively.

Assessing Supply Chain Transparency

Suppliers should be asked to provide complete documentation on the origin and handling of raw materials throughout the supply chain. 

Cost Considerations

While cost is a significant factor, it should not be accompanied by a poor-quality product. Investing in high-quality MCC can prevent issues in tablet formulation and production, eventually saving costs associated with product recalls or compliance issues that might arise in the future. Furthermore, working with suppliers who prioritize sustainability and quality can prevent hidden costs related to non-compliance and market reputation.

Conclusion 

Microcrystalline Cellulose (MCC) is a popular excipient used in solid dosage form development. Its unique physicochemical properties allow it to serve as a multifunctional excipient that enhances tablet compressibility, stability, and performance. When sourcing MCC, it’s integral to ensure that your potential supplier maintains stringent quality control measures. You can do so by evaluating physicochemical properties and checking for compliance with pharmacopeial standards—both of which are prerequisites to maintaining consistency and efficacy in pharmaceutical formulations. 

Once you have evaluated a few suppliers, the next step is to carefully develop a vendor shortlist followed by a careful selection of reputable suppliers, thorough audits, and a commitment to sustainable and transparent procurement practices. 

However, it doesn’t end here. Continuous monitoring of MCC's performance in your formulations, along with ongoing supplier relationships will help you maintain a consistent supply of high-quality excipients that meet regulatory requirements.