(T1130-11-70) Application of Colloidal MCC and Xanthan in Challenging Suspension Formulation

Purpose: Colloidal MCC Avicel® RC-591 is widely used in various suspension formulations as a suspending agent in food and pharmaceutical industry due to its excellent thixotropic property ^[1]. Xanthan gum is an exocellular heteropolysaccharide produced by a distinct fermentation process and could be used as suspending agent and thickener in pharmaceutical suspension dosage form due to high at-rest viscosity ^[2]. Although Avicel® RC-591 based suspensions are very stable, there are some challenging conditions for Avicel® RC-591 based suspension. Flocculation or sedimentation may occur due to neutralization of the negative charge of CMC. Low pH condition (pH < 4), divalent cations, acidic drug and anionic surfactant are main reasons for such stability issues. Prior research showed that combination of Avicel® RC-591 and xanthan gum could be helpful to get more robust and stable suspension formulation in these challenging conditions ^[3]. In this study, xanthan was utilized together with Avicel® RC-591 as stabilizers in above challenging suspension formulations to evaluate their synergistic effect on improvement of suspending stability. Although Avicel^® RC-591 based suspensions are very stable, there are some challenging conditions for Avicel® RC-591 based suspension. Flocculation or sedimentation may occur due to neutralization of the negative charge of CMC. Low pH condition (pH < 4), divalent cations, acidic drug and anionic surfactant are main reasons for such stability issues. Prior research showed that combination of Avicel® RC-591 and xanthan gum could be helpful to get more robust and stable suspension formulation in these challenging conditions ^[3]. In this study, xanthan was utilized together with Avicel® RC-591 as stabilizers in above challenging suspension formulations to evaluate their synergistic effect on improvement of suspending stability.

Methods: Rheological properties of colloidal MCC suspension and colloidal MCC/xanthan suspension were characterized and compared to understand the impact of combination of colloidal MCC and xanthan on suspension rheological properties. Challenging suspension formulations containing acidic ingredient, anionic surfactant and divalent cations were prepared with colloidal MCC or combination of colloidal MCC and xanthan as suspending agents. The synergistic effect of colloidal MCC and xanthan were evaluated in ibuprofen suspension and paracetamol suspension low pH formulations. Suspension particle morphology was observed by polarized light microscope. Rheological properties of suspension formulations, such as thixotropy and gel strength, were analyzed by TA Discovery HR-3 rheometer. Stability test of challenging suspension formulation was performed as well.

Results: The thixotropy and gel strength profiles of both colloidal MCC suspension and colloidal MCC/xanthan suspension are shown in Figure 1 and Figure 2. As shown in Figure 3 and Figure 4, pure Avicel® RC-591 based challenging suspension formulations containing acidic ingredient, anionic surfactant and divalent cations will result in aggregation or sedimentation issues while adding xanthan gum GRINDSTED® Clear 80 as protective colloid can significantly improve the stability of these challenging suspension formulations.

Conclusion: According to this study we can see pure Avicel® RC-591 suspensions are not stable under some challenging conditions like contacting with SLS, citric acid or calcium ions. Xanthan is an effectively protective colloid to improve the stability of Avicel® RC-591 based suspension in such conditions. Case studies of paracetamol suspension showed that combination of Xanthan and Avicel® RC-591 provide good stability and no obviously visible sedimentation happened in ambient condition for 2 months.

References: [1] Aulton M.E. "Suspension" Pharmaceutics-the Science of Dosage Form Design, Churchill Livingstone,
Edinburgh Second Edition, 2002; Page No. 84-86, 273.
[2] Sanderson G.R., Applications of Xanthan Gum[J]. The British polymer Journal, 1981,13
[3] pH Impact on the Suspension Capability of Colloidal MCC. Yeli Zhang. AAPS ePoster Library. Zhang
Y. 10/18/2022; 367046; T1230-12-71