Curcumin-loaded Soluplus® based ternary solid dispersions with enhanced solubility and biological activities

This presentation summarizes a study on improving the properties of curcumin, a natural compound with anti-inflammatory and antioxidant benefits. The research focuses on creating ternary solid dispersions using different polymers to increase curcumin's poor water solubility. The most effective formulation, using the polymer Soluplus®, was found to significantly enhance the drug's solubility, dissolution rate, and biological activities, including its antioxidant, antibacterial, and anti-inflammatory properties. The study concludes that this method is a promising approach for developing formulations of other poorly water-soluble drugs.

1. Curcumin-loaded soluplus® based ternary solid dispersions with Enhanced solubility, dissolution, and biological activities Presented by Mr.Sumit Mundhe B. Pharm Memoona Ishtiaq, Hina Manzoor, Ikram Ullah Khan, Sajid Asghar, Muhammad Irfan, Norah A. Albekairi, Abdulrahman Alshammari, Abdulrahman F. Alqahtani, Saad Alotaibi, Rabia Munir, Pervaiz A. Shah, Liaqat Hussain, Muhammad Abubakar Saleem, Fizza Abdul Razzaq, Syed Haroon Khalid* Date:  2024-07-14 Journal:  Heliyon DOI:  10.1016/j.heliyon.2024.e34636

2. Contents Introduction Previous Research Insights Formulation of Ternary Solid Dispersions Characterization Study summary Conclusion References 03-04-2025 RSCP, Buldhana. 2

3. Introduction to Curcumin Definition:  Curcumin is a natural polyphenolic compound. Source:   O btained from the root of plant Curcuma longa Therapeutic Potential:  anti-inflammatory, antioxidant, and antibacterial properties. Limitations:  Curcumin, a plant extract, is characterized by its structure consisting of two polar phenyl rings, two hydroxyl and ortho-methoxy groups, and an aliphatic chain (C7) which makes curcumin essentially insoluble in water. Focus of Study:  Development of ternary solid dispersions to improve curcumin's properties. 03-04-2025 RSCP, Buldhana. 3

4. Solid Dispersions (SD):  A method to enhance solubility and bioavailability. Binary vs. Ternary Systems:  Ternary systems are more effective than binary systems. Polymers Used:   Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 in combination with HPMC E5 (binary carrier) Techniques Employed:  solvent evaporation (SE) were used. Formulation Goals:  Achieve higher solubility and stability. Selection Criteria:  Choosing the right polymer is critical for success . 03-04-2025 RSCP, Buldhana. 4   Solid Dispersion Techniques

5. 03-04-2025 RSCP, Buldhana. 5 Previous Research Insights Earlier Studies:  Focused on binary solid dispersions. Polymers Tested:  BSA, HPMC E5, PEG 6000, and PVP K30 were previously used. Findings:  Binary systems showed some improvement in solubility. Formulation Techniques:  Kneading and solvent evaporation were utilized. Key Formulations:  CUR: HPMC E5 (1:4 SE) and CUR: PVP K30 (1:4 KN). Research Gap:  Limited studies on ternary solid dispersions for curcumin.

6. 03-04-2025 RSCP, Buldhana. 6 Formulation of Ternary Solid Dispersions Polymers chosen for this study are Soluplus®, Syloid® XDP 3150, Syloid® 244 and Poloxamer® 188 Overall, the solubility value of curcumin was highest with Soluplus® followed by Poloxamer 188®, Syloid ® XDP 3150 and Syloid® 244. An increase in con-centration of soluplus® from 5 to 20 percent notably enhanced the solubility from 70.302 ± 5.32 μg/ml (F1) to 125.302 ± 4.87 μg/ml (F2) and 186.38 ± 3.95 μg/ml (F3)

7. 03-04-2025 RSCP, Buldhana. 7 Sr. no Formulation code Binary carrier Drug: HPMC (W/W) Ternary Carrier Percentage of ternary polymer (W/W) 1 F1,F2,F3 HPMC E5 1:4 Soluplus® 5 %,10 %, 20 % 2 F4,F5,F6 HPMC E5 1:4 Poloxamer 188® 5 %,10 %, 20 % 3 F7,F8,F9 HPMC E5 1:4 Syloid® XDP 5 %,10 %, 20 % 4 F10,F11,F12 HPMC E5 1:4 Syloid® 244 5 %,10 %, 20 %

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9. 03-04-2025 RSCP, Buldhana. 9 FTIR Analysis Technique Overview: Fourier Transform Infrared Spectroscopy (FTIR) is used to identify functional groups and molecular interactions in solid dispersions. Key Findings: FTIR spectra indicated characteristic peaks of curcumin and Soluplus®. Shifts in peak positions suggest interactions between curcumin and the polymer. Significance: Confirmed the successful incorporation of curcumin into the solid dispersion. Provided insights into the chemical stability of the formulation. Conclusion: FTIR analysis supports the hypothesis of enhanced solubility due to molecular interactions in the solid dispersion.

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11. 03-04-2025 RSCP, Buldhana. 11 X-ray Diffraction Analysis Purpose of XRD:  To analyze the physical state of curcumin in dispersions. Results for Pure Curcumin:  Exhibited distinctive diffraction peaks, indicating crystallinity. Soluplus® Characteristics:  Showed no distinctive peaks, confirming amorphous nature. Impact of Formulations:  Reduction in peaks in F1, F2, and F3 formulations. Amorphous Conversion:  Successful conversion of curcumin to an amorphous form. Correlation with Solubility:  Amorphous forms generally enhance solubility.

12. 03-04-2025 RSCP, Buldhana. 12 SEM Analysis Technique Overview: Scanning Electron Microscopy (SEM) provides detailed images of the surface morphology of solid dispersions. Key Findings : SEM images revealed a uniform distribution of curcumin within the Soluplus® matrix. The morphology of the solid dispersions appeared smooth and amorphous. Significance : The absence of crystalline structures indicates successful conversion of curcumin to an amorphous state. Morphological characteristics correlate with improved solubility and dissolution rates. Conclusion : SEM analysis visually confirms the effective formulation of curcumin in the solid dispersion system

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14. 03-04-2025 RSCP, Buldhana. 14 DSC Analysis Technique Overview: Differential Scanning Calorimetry (DSC) is employed to study thermal properties and stability of the solid dispersions. Key Findings: DSC thermograms of pure curcumin showed a sharp melting endotherm, indicating its crystalline nature. Solid dispersions exhibited a broad endothermic peak, suggesting a change to an amorphous state. Significance: The thermal analysis indicates improved stability of curcumin in the solid dispersion. The absence of sharp melting points in formulations suggests enhanced solubility and reduced crystallization tendency. Conclusion:  DSC analysis provides critical insights into the thermal behavior of curcumin-loaded solid dispersions, supporting their potential for improved drug delivery.

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16. 03-04-2025 RSCP, Buldhana. 16 Antioxidant Activity Assessment Method Used:  DPPH radical scavenging assay to evaluate antioxidant activity. Control Setup:  2 mL of DPPH solution (0.1 mM, Methanol) as control. Optimized Preparation:  200 μL of the optimized formulation was tested. Results for F3:  Showed 93% ± 5.30 antioxidant activity. Comparison with CUR:  CUR exhibited 69% ± 4.79 antioxidant activity. Significance of Findings:  Enhanced antioxidant activity indicates better formulation.

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18. 03-04-2025 RSCP, Buldhana. 18 Antibacterial Activity Evaluation In-vitro Investigation:  Assessed antibacterial properties of F3. Tested Strains:  Included both gram-positive and gram-negative bacteria. Most Susceptible Strain:  Staphylococcus aureus showed the highest susceptibility. Zone of Inhibition:  F3 exhibited a zone of inhibition of 24 mm ± 2.87. Comparison with CUR:  Enhanced antibacterial activity in the optimized formulation. Implications for Use:  Potential for therapeutic applications against bacterial infections.

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21. 03-04-2025 RSCP, Buldhana. 21 Anti-inflammatory Activity Assessment Methodology:  In vitro assessment of anti-inflammatory properties. BSA Denaturation Test:  Evaluated the protective effect on BSA. Results for F3:  Markedly protected BSA with 80% ± 3.16 inhibition. Comparison with CUR:  CUR showed only 49% ± 2.91 inhibition. Significance of Results:  Indicates potential for anti-inflammatory applications. Broader Implications:  Could enhance therapeutic efficacy in inflammatory conditions.

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23. 03-04-2025 RSCP, Buldhana. 23 Conclusion Overall Impact:  Ternary solid dispersions are effective for curcumin delivery. Enhanced Properties:  Improved solubility and biological activities were achieved. F3 as a Model System:  Represents a promising formulation for hydrophobic drugs. Clinical Relevance:  Potential to improve therapeutic outcomes for curcumin. Next Steps:  Investigate long-term stability and real-world applications.

24. 03-04-2025 RSCP, Buldhana. 24 Reference F. Fallahi, et al., Curcumin and inflammatory bowel diseases: from in vitro studies to clinical trials, Mol. Immunol. 130 (2021) 20–30 . M. Pulido-Moran, et al., Curcumin and health, Molecules 21 (3) (2016) 264 . S. Prasad, et al., Metal–curcumin complexes in therapeutics: an approach to enhance pharmacological effects of curcumin, Int. J. Mol. Sci. 22 (13) (2021) 7094 . B. Zheng, D.J. McClements, Formulation of more efficacious curcumin delivery systems using colloid science: enhanced solubility, stability, and bioavailability, Molecules 25 (12) (2020) 2791 . R.J. Chokshi, et al., Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution—pros and cons, Drug Deliv. 14 (1) (2007) 33–45 . Y. Huang, W.-G. Dai, Fundamental aspects of solid dispersion technology for poorly soluble drugs, Acta Pharm. Sin. B 4 (1) (2014) 18–25 . Y. Lu, et al., Understanding the relationship between wettability and dissolution of solid dispersion, Int. J. Pharm. 465 (1–2) (2014) 25–31 .

25. 03-04-2025 RSCP, Buldhana. 25 Thank You !