Mucoadhesive buccal tablets incorporating curcumin solid dispersion as a potential approach for enhancing curcumin therapeutic efficacy in oral inflammatory disorders

Document Type : Original Article

Authors

1 Central Lab, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.

2 Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.

3 Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt.

Abstract

Curcumin (cur) elicits a wide spectrum of potent responses for local treatment of oral disorders. However, its clinical use in the oral cavity is limited by its poor solubility and chemical instability at salivary pH. This study aims to develop cur mucoadhesive buccal tablet formulation with enhanced cur solubility and stability. For this purpose, a rapidly dissolving solid dispersion (SD) was developed using PVP (Kollidon®25). In addition, chemical stability in phosphate buffer saline (PBS) pH 6.8 was investigated for the first time using different stabilizers to ensure cur stability for in-vitro and in-vivo studies. After addressing solubility and stability challenges, buccal tablets formulations were developed using Hydroxypropyl methylcellulose (HPMC) and Carboxymethyl cellulose (CMC sodium) mixture in different ratios with or without SLS as stabilizer.
Tablets containing HPMC.K15M: CMC sodium (5:1), SD (1:3), and 15 mg SLS showed the best results regarding mucoadhesive strength, in-vivo residence time, and release rate profile and were considered as the optimized formulation. The optimized formulation ensured cur stability as well as a controlled release rate, with considerable cur levels in saliva for over 12h. Preliminary clinical evaluation showed remarkable anti-inflammatory and healing effects in patients with aphthous ulcer, concluding that cur stabilized mucoadhesive formulation can efficiently treat various inflammatory oral diseases.

Highlights

  • Amorphous cur solid dispersion improved cur solubility problem at low expenses.
  • SLS exhibited excellent cur stability in in-vitro and in-vivo studies.
  • Mucoadhesive tablets increased the contact time resulting in rapid pain relief.
  • Cur stabilized mucoadhesive tablet showed a promising healing effect.

Keywords

Main Subjects

References

  1. Mitra S, Tareq AM, Das R, Emran TB, Nainu F, Chakraborty AJ, et al. Polyphenols: A first evidence in the synergism and bioactivities. Food Reviews International. 2023;39(7):4419-41.
  2. Obeid MA, Alsaadi M, Aljabali AA. Recent updates in curcumin delivery. Journal of liposome research. 2023;33(1):53-64.
  3. Abolfazli S, Butler AE, Jamialahmadi T, Sahebkar A. A Golden Shield: The Protective Role of Curcumin Against Liver Fibrosis. Current Medicinal Chemistry. 2024.
  4. Murtadlo AAA, Ansori ANM, Dhea V, Turista DR, Rosadi I, Jakhmola V, et al. A Mini Review of Curcuma longa: Antimicrobial Properties. 2024.
  5. Das D, Mitra A, Zaky MY, Pathak S, Banerjee A. A Review on the Efficacy of Plant-derived Bio-active Compounds Curcumin and Aged Garlic Extract in Modulating Cancer and Age-related Diseases. Current Reviews in Clinical and Experimental Pharmacology Formerly Current Clinical Pharmacology. 2024;19(2):146-62.
  6. Dunsmore KE, Chen PG, Wong HR. Curcumin, a medicinal herbal compound capable of inducing the heat shock response. Critical care medicine. 2001;29(11):2199-204.
  7. Kuhad A, Pilkhwal S, Sharma S, Tirkey N, Chopra K. Effect of curcumin on inflammation and oxidative stress in cisplatin-induced experimental nephrotoxicity. Journal of agricultural and food chemistry. 2007;55(25):10150-5.
  8. Ohori H, Yamakoshi H, Tomizawa M, Shibuya M, Kakudo Y, Takahashi A, et al. Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer. Molecular cancer therapeutics. 2006;5(10):2563-71.
  9. Mehta P, Bhavasar R, Ajith NA, Bhavsar RP, Bahammam MA, Bakri MMH, et al., Assessing the effect of curcumin on the oral mucosal cytomorphometry and candidal species specificity in tobacco users: a pilot study. Healthcare; 2022: MDPI.
  10. Hajifathali S, Lesan S, Lotfali E, Salimi-Sabour E, Khatibi M. Investigation of the antifungal effects of curcumin against nystatin-resistant Candida albicans. Dental Research Journal. 2023;20.
  11. Chen CW, Hsieh MJ, Ju PC, Hsieh YH, Su CW, Chen YL, et al. Curcumin analog HO‐3867 triggers apoptotic pathways through activating JNK1/2 signalling in human oral squamous cell carcinoma cells. Journal of Cellular and Molecular Medicine. 2022;26(8):2273-84.
  12. Al-Askar M, AlMubarak AM, Alqutub MN, Mokeem S, Javed F, Vohra F, et al. Analgesic Efficacy of Curcuma longa (Curcumin) after Surgical Periodontal Therapy. Oral Health Prev Dent. 2022;20:19-26.
  13. Sterniczuk B, Rossouw PE, Michelogiannakis D, Javed F. Effectiveness of Curcumin in Reducing Self-Rated Pain-Levels in the Orofacial Region: A Systematic Review of Randomized-Controlled Trials. International Journal of Environmental Research and Public Health. 2022;19(11):6443.
  14. Huang X, Liu Y, Wang Q, Rehman HM, Horváth D, Zhou S, et al. Brief literature review and comprehensive bioinformatics analytics unravel the potential mechanism of curcumin in the treatment of periodontitis. BMC Oral Health. 2023;23(1):469.
  15. Nair VV, Cabrera P, Ramírez-Lecaros C, Jara MO, Brayden DJ, Morales JO. Buccal delivery of small molecules and biologics: of mucoadhesive polymers, films, and nanoparticles–An update. International Journal of Pharmaceutics. 2023:122789.
  16. Jana BK, Singh M, Dutta RS, Mazumder B. Current drug delivery strategies for buccal cavity ailments using mouth dissolving wafer technology: a comprehensive review on the present state of the art. Current Drug Delivery. 2024;21(3):339-59.
  17. Dattatray JA, Nalawade DD, Prasad KC. A review on mucoadhesive buccal drug delivery. Research Journal of Science and Technology. 2023;15(3):153-60.
  18. Khater A-J, Almurisi SH, Mahmood S, Madheswaran T, Chatterjee B, Sri P, et al. Strategies to improve the stability of amorphous solid dispersions in view of the hot melt extrusion (HME) method. International Journal of Pharmaceutics. 2023:123536.
  19. Budiman A, Handini AL, Muslimah MN, Nurani NV, Laelasari E, Kurniawansyah IS, et al. Amorphous Solid Dispersion as Drug Delivery Vehicles in Cancer. Polymers. 2023;15(16):3380.
  20. Li J, Wang Y, Yu D. Effects of Additives on the Physical Stability and Dissolution of Polymeric Amorphous Solid Dispersions: a Review. AAPS PharmSciTech. 2023;24(7):175.
  21. Valenti S, Arioli M, Jamett A, Tamarit JL, Puiggalí J, Macovez R. Amorphous solid dispersions of curcumin in a poly (ester amide): Antiplasticizing effect on the glass transition and macromolecular relaxation dynamics, and controlled release. International journal of pharmaceutics. 2023;644:123333.
  22. Xi Z, Fei Y, Wang Y, Lin Q, Ke Q, Feng G, et al. Solubility improvement of curcumin by crystallization inhibition from polymeric surfactants in amorphous solid dispersions. Journal of Drug Delivery Science and Technology. 2023;83:104351.
  23. Siripruekpong W, Issarachot O, Kaewkroek K, Wiwattanapatapee R. Development of Gastroretentive Carriers for Curcumin-Loaded Solid Dispersion Based on Expandable Starch/Chitosan Films. Molecules. 2023;28(1):361.
  24. Han J, Wei Y, Li L, Song Y, Pang Z, Qian S, et al. Gelation elimination and crystallization inhibition by co-amorphous strategy for amorphous curcumin. Journal of Pharmaceutical Sciences. 2023;112(1):182-94.
  25. Feng Y, Li B, Yang L, Liu Y. Co-amorphous delivery systems based on curcumin and hydroxycinnamic acids: Stabilization, solubilization, and controlled release. LWT. 2022;170:114091.
  26. Maleki Dizaj S, Sharifi S, Tavakoli F, Hussain Y, Forouhandeh H, Hosseiniyan Khatibi SM, et al. Curcumin-Loaded silica nanoparticles: Applications in infectious disease and food industry. Nanomaterials. 2022;12(16):2848.
  27. Tran T-T, Chua A, Pu S, Park J-W, Hadinoto K. Maintaining supersaturation generation and protein integrity of amorphous curcumin-albumin nanoplex during storage by freeze drying with trehalose. Journal of Drug Delivery Science and Technology. 2023;83:104425.
  28. Teixeira C, Mendonca L, Bergamaschi M, Queiroz R, Souza G, Antunes L, et al. Microparticles containing curcumin solid dispersion: stability, bioavailability and anti-inflammatory activity. AAPS PharmSciTech. 2016;17(2):252-61.
  29. Chuah AM, Jacob B, Jie Z, Ramesh S, Mandal S, Puthan JK, et al. Enhanced bioavailability and bioefficacy of an amorphous solid dispersion of curcumin. Food chemistry. 2014;156:227-33.
  30. Song I-S, Cha J-S, Choi M-K. Characterization, in vivo and in vitro evaluation of solid dispersion of curcumin containing d-α-Tocopheryl polyethylene glycol 1000 succinate and mannitol. Molecules. 2016;21(10):1386.
  31. Li J, Lee IW, Shin GH, Chen X, Park HJ. Curcumin-Eudragit® E PO solid dispersion: a simple and potent method to solve the problems of curcumin. European Journal of Pharmaceutics and Biopharmaceutics. 2015;94:322-32.
  32. Wan S, Sun Y, Qi X, Tan F. Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech. 2012;13(1):159-66.
  33. Parikh A, Kathawala K, Song Y, Zhou X-F, Garg S. Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability. Drug delivery and translational research. 2018:1-17.
  34. Zhang Q, Suntsova L, Chistyachenko YS, Evseenko V, Khvostov MV, Polyakov NE, et al. Preparation, physicochemical and pharmacological study of curcumin solid dispersion with an arabinogalactan complexation agent. International journal of biological macromolecules. 2019;128:158-66.
  35. Kaewnopparat N, Kaewnopparat S, Jangwang A, Maneenaun D, Chuchome T, Panichayupakaranant P. Increased solubility, dissolution and physicochemical studies of curcumin-polyvinylpyrrolidone K-30 solid dispersions. World academy of science, engineering and technology. 2009;55:229-34.
  36. Alves TF, Chaud MV, Grotto D, Jozala AF, Pandit R, Rai M, et al. Association of silver nanoparticles and curcumin solid dispersion: antimicrobial and antioxidant properties. AAPS PharmSciTech. 2018;19(1):225-31.
  37. Hernandez-Patlan D, Solis-Cruz B, Pontin KP, Latorre JD, Baxter MFA, Hernandez-Velasco X, et al. Evaluation of a Solid Dispersion of Curcumin With Polyvinylpyrrolidone and Boric Acid Against Salmonella Enteritidis Infection and Intestinal Permeability in Broiler Chickens: A Pilot Study. Frontiers in microbiology. 2018;9:1289.
  38. Paradkar A, Ambike AA, Jadhav BK, Mahadik KR. Characterization of curcumin–PVP solid dispersion obtained by spray drying. International Journal of Pharmaceutics. 2004;271(1):281-6.
  39. Hazzah HA, Farid RM, Nasra MM, Hazzah WA, El-Massik MA, Abdallah OY. Gelucire-based nanoparticles for curcumin targeting to oral mucosa: preparation, characterization, and antimicrobial activity assessment. Journal of pharmaceutical sciences. 2015;104(11):3913-24.
  40. El-Refaie WM, Elnaggar YS, El-Massik MA, Abdallah OY. Novel curcumin-loaded gel-core hyaluosomes with promising burn-wound healing potential: development, in-vitro appraisal and in-vivo studies. International journal of pharmaceutics. 2015;486(1-2):88-98.
  41. Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive delivery systems. I. Evaluation of mucoadhesive polymers for buccal tablet formulation. Drug development and industrial pharmacy. 2004;30(9):985-93.
  42. Hazzah HA, Farid RM, Nasra MM, Zakaria M, Gawish Y, El-Massik MA, et al. A new approach for treatment of precancerous lesions with curcumin solid–lipid nanoparticle-loaded gels: in vitro and clinical evaluation. Drug delivery. 2016;23(4):1409-19.
  43. Hazzah HA, Farid RM, Nasra MM, EL-Massik MA, Abdallah OY. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization. International journal of pharmaceutics. 2015;492(1-2):248-57.
  44. Association WM. World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization. 2001;79(4):373.
  45. Vasconcelos T, Marques S, das Neves J, Sarmento B. Amorphous solid dispersions: rational selection of a manufacturing process. Advanced drug delivery reviews. 2016;100:85-101.
  46. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN pharmaceutics. 2012;2012.
  47. Xu D-H, Wang S, Jin J, Mei X-T, Xu S-B. Dissolution and absorption researches of curcumin in solid dispersions with the polymers PVP. Asian J Pharmacodyn Pharmacokinet. 2006;6(4):343-9.
  48. Frizon F, de Oliveira Eloy J, Donaduzzi CM, Mitsui ML, Marchetti JM. Dissolution rate enhancement of loratadine in polyvinylpyrrolidone K-30 solid dispersions by solvent methods. Powder technology. 2013;235:532-9.
  49. Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochemical pharmacology. 2008;75(4):787-809.
  50. Lee BH, Choi HA, Kim M-R, Hong J. Changes in chemical stability and bioactivities of curcumin by ultraviolet radiation. Food Science and Biotechnology. 2013;22(1):279-82.
  51. Seo S-W, Han H-K, Chun M-K, Choi H-K. Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier. International journal of pharmaceutics. 2012;424(1-2):18-25.
  52. Patel VF, Liu F, Brown MB. Advances in oral transmucosal drug delivery. Journal of controlled release. 2011;153(2):106-16.
  53. Wang Z, Leung MH, Kee TW, English DS. The role of charge in the surfactant-assisted stabilization of the natural product curcumin. Langmuir. 2009;26(8):5520-6.
  54. Nokhodchi A, Hassan-Zadeh D, Monajjem-Zadeh F, Taghi-Zadeh N. Effect of various surfactants and their concentration on controlled release of captopril from polymeric matrices. Acta Pharmaceutica. 2008;58(2):151-62.
  55. Nafee NA, Ismail FA, Boraie NA, Mortada LM. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing. International journal of pharmaceutics. 2003;264(1-2):1-14.

 

Journal of Advanced Pharmaceutical Sciences
Volume 1, Issue 2
June 2024
Pages 100-117

Files

Share

How to cite

Statistics