(T1530-06-40) Application of Colloidal Microcrystalline Cellulose in Reconstitutable Suspension

Purpose: Reconstitutable suspension offers several advantages, including enhanced stability and extended shelf life, as the active pharmaceutical ingredient (API) remains in a dry state until reconstitution. This formulation is particularly advantageous for APIs that are sensitive to moisture or have limited stability in liquid form. With proper formulation, the reconstitutable powder can be easily converted into a liquid form just before use, providing a convenient and effective solution for both healthcare providers and patients. The choice of suspending agent is crucial for the effectiveness and stability of reconstitutable suspensions. An appropriate suspending agent facilitates easy reconstitution, allowing the powder to disperse quickly and uniformly when mixed with water. It also keeps the API uniformly dispersed in the reconstituted suspension, preventing sedimentation and ensuring consistent dosing. Colloidal microcrystalline cellulose (cMCC) is a well-established suspending agent that forms a strong gel-like network, effectively suspending the API in suspension formulations. This study aimed to assess the performance of a specific pharmaceutical-grade cMCC, Avicel® CL-611, in reconstitutable suspension applications. Additionally, the study outlined commonly used analytical methods for evaluating reconstitutable suspensions.

Methods: As shown in Table 1, a calcium carbonate model formulation was used to evaluate the suspending capability of Avicel® CL-611 for reconstitutable suspensions. To study the effectiveness and variability, three dry powder blends, each containing Avicel® CL-611 from different lots, were prepared. The dry powder formulations were created by proportionally weighing calcium carbonate, Avicel® CL-611, sucrose, and potassium sorbate into a wide-mouth plastic jar, followed by uniform blending using a turbula mixer at 49 rpm for 15 minutes. Three 600 ml reconstituted suspensions were prepared from the three dry powder blends. For each suspension, 360 grams of water was added to the dry powder blend and mixed using a turbula mixer at 101 rpm for 5 minutes. This method was developed to simulate the process of hand shaking to prepare reconstitutable suspensions. Microscopy analysis was performed on all reconstituted suspensions using a Nikon Eclipse Ci Microscope to verify their uniformity. The initial viscosity and the viscosity after 24 hours of rest at room temperature were measured for each suspension using a Brookfield RVT viscometer. Additionally, comprehensive rheological analysis was conducted with a TA-Instruments DHR3 rheometer, utilizing a 50 mm parallel plate geometry with a 1.8 mm gap size at 20°C. All model suspensions were stored in a refrigerator at 4°C for stability studies over a period of up to three weeks.

Results: Figure 1 showed representative microscope images of reconstituted suspensions both initially and after three weeks of storage at 4°C. The Avicel® CL-611 was fully dispersed within the liquid suspension, effectively suspending calcium carbonate particles throughout the formulation. Notably, no phase separation was observed during the three-week stability study, indicating robust suspension stability. Figure 2 illustrates the G’ and G” values, as well as the thixotropic properties of the suspension, demonstrating its stability over the three-week period. The G’ and G” values indicate the gel-like network formed by Avicel® CL-611. The stability of these values throughout storage confirms the integrity of the gel-like structure, ensuring uniform dispersion of calcium carbonate and preventing sedimentation, which is crucial for consistent dosing. The strong thixotropic behavior exhibited by Avicel® CL-611 ensures user-friendly application, allowing the suspension to flow easily when shaken or stirred, yet remain stable when at rest. The consistent thixotropic properties throughout the storage period indicate a stable reconstituted suspension, demonstrating the reliability and effectiveness of Avicel® CL-611 as a suspending agent in reconstitutable suspensions.

Conclusion: Colloidal microcrystalline cellulose is a highly effective suspending agent, known for its stable and robust suspending capabilities. However, only specific types of cMCC are suitable for use in reconstitutable suspensions. The study's findings demonstrated the effectiveness of Avicel® CL-611 as a suspending agent for reconstitutable suspensions, emphasizing its ability to form a stable gel-like network through the preparation method for reconstitutable suspensions. This stable gel-like network maintains the suspension's properties over extended storage periods. The thixotropic nature of the suspension further enhances its user-friendliness, allowing it to flow easily when shaken or stirred while remaining stable at rest. These characteristics make Avicel® CL-611 an ideal component in the formulation of reconstitutable suspensions, ensuring both stability and ease of use for the end user.

References: 1. Kaushal Arora, A Review on Pharmaceutical Suspension and Its Advancemement, Annals of Clinical Case Reports – Medicine, 2022.


Table 1. Formulation details


Figure 1. Microscope images of reconstituted suspension


Figure 2. Rheological analysis of reconstituted suspension