The Drying Temperature Impact on Curcumin - Piperine Dissolution and Its Kinetic Release: Application of A Spray Dryer on the Preparation of Solid Dispersion-based Microparticle Containing Curcuma longa and Piper Nigrum Extracts

Year 2023, Volume: 27 Issue: 4, 1329 - 1337, 28.06.2025

Siska Ayu Purnamasari Dewi Setyaningsih

Abstract

After oral administration, low water solubility and rapid pre-systemic metabolism contribute to curcumin's poor bioavailability. To solve the bioavailability issue, piperine, a natural bioenhancer, can be coupled with curcumin in a solid dispersion-based microparticle formulation (SD). This study's objective was to understand drying temperature's effect on the yield and dissolution behaviour of curcumin and piperine in the SD containing C.longa and P.nigurm extracts at a weight ratio of 3:1. The SD was prepared on a solvent method and used polyvinylpyrrolidone K30 as a carrier. Spray drying was operated at 105°C, 115°C, and 125°C to evaporate the solvent. The yield and dissolution behaviour of curcumin and piperine were their defining characteristics, and the dissolution efficiency (DE) was used to compare the dissolution profiles. The kinetic release model of curcumin and piperine was determined using DDsolver software. The results demonstrate that the SD's yield increases as inlet temperature increases, from 33.60% at 105°C to 35.75% at 115°C to 39.30% at 125°C. The dissolution of curcumin and piperine from the SD increases along with the rise in drying temperature. Variation in drying temperature provides a different kinetic model of curcumin and piperine release. The Weibull model describes the release kinetic of curcumin and piperine at almost used drying temperatures; however, the release of piperine from the SD prepared at 125°C fits the zero-order model.

Keywords

Curcumin , ddsolver; dissolution , kinetic release; piperine , solid dispersion , spray drying

References

• [1] Menon VP, Sudheer AR. Antioxidant and anti-inflammatory properties of curcumin. Adv Exp Med Biol. 2007;595:105-125. https://doi.org/10.1007/978-0-387-46401-5_3.
• [2] Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A. Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades? J Cell Physiol. 2018;233:830–848. https://doi.org/10.1002/jcp.25778.
• [3] Sufiawati I, Gunawan I, Wijaya I, Rusdiana T, Subarnas A. Reduction of salivary tumor necrosis factor alpha levels in response to magic mouthwash with Curcuma xanthorriza in cancer patients undergoing chemotherapy. J Res Pharm. 2018;23:55–61. https://doi.org/10.12991/jrp.2018.108.
• [4] Wang R, Han J, Jiang A, Huang R, Fu T, Wang L, Zheng Q, Li W, Li J. Involvement of metabolism-permeability in enhancing the oral bioavailability of curcumin in excipient-free solid dispersions co-formed with piperine. Int J Pharm. 2019;561:9-18. https://doi.org/10.1016/j.ijpharm.2019.02.027.
• [5] Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47-60. https://doi.org/10.1016/s0939-6411(00)00076-x.
• [6] 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):159-166. https://doi.org/10.1208/s12249-011-9732-9.
• [7] Kharat M, Du Z, Zhang G, McClements DJ. Physical and chemical stability of curcumin in aqueous solutions and emulsions: Impact of pH, temperature, and molecular environment. J Agric Food Chem. 2017;65(8):1525-1532. https://doi.org/10.1021/acs.jafc.6b04815.
• [8] Wahlström B, Blennow G. A study on the fate of curcumin in the rat. Acta Pharmacol Toxicol (Copenh). 1978;43:86–92. https://doi.org/10.1111/j.1600-0773.1978.tb02240.x.
• [9] Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Medica. 1998;64(4):353–356. https://doi.org/10.1055/s-2006-957450.
• [10] Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, Kamani DR, Chauhan BN. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. ScientificWorldJournal. 2012;2012:637953. https://doi.org/10.1100/2012/637953.
• [11] Patil VM, Das S, Balasubramanian K. Quantum chemical and docking insights into bioavailability enhancement of curcumin by piperine in pepper. J Phys Chem A. 2016;120:3643–3653. https://doi.org/https:/doi.org/10.1021/acs.jpca.6b01434.
• [12] Dwi S, Febrianti S, Zainul A, Retno S. PEG 8000 increases solubility and dissolution rate of quercetin in solid dispersion system. Marmara Pharm J. 2018;22:259–266. https://doi.org/10.12991/mpj.2018.63.
• [13] Sakhare SS, Sayyad FJ. Studies on Ocimum basilicum mucilage based solid dispersions of indomethacin for enhancement of dissolution rate. J Res Pharm. 2019;23:832–838. https://doi.org/10.35333/jrp.2019.31.
• [14] Szabó E, Záhonyi P, Brecska D, Galata DL, Mészáros LA, Madarász L, Csorba K, Vass P, Hirsch E, Szafraniec-Szczęsny J, Csontos I, Farkas A, Van denMooter G, Nagy ZK, Marosi G. Comparison of Amorphous Solid Dispersions of Spironolactone Prepared by Spray Drying and Electrospinning: The Influence of the Preparation Method on the Dissolution Properties. Mol Pharm. 2021;18(1):317-327. https://doi.org/10.1021/acs.molpharmaceut.0c00965.
• [15] Ha E-S, Hyung Choi D, Baek I, Park H, Kim M-S. Enhanced oral bioavailability of resveratrol by using neutralized Eudragit E solid dispersion prepared via spray drying. Antioxidants (Basel). 2021;10(1):90. https://doi.org/10.3390/antiox10010090.
• [16] Kumar B. Solid Dispersion-A Review. PharmaTutor. 2017;5:24–29.
• [17] Robaina-Mesa M, López-Hernández OD, Rodríguez-Chanfrau CJE, Nogueira-Mendoza A. Spray dried aqueous extract of Orthosiphon aristatus blume (Java tea). Braz J Pharm Sci. 2017;53:1–5. http://dx.doi.org/10.1590/s2175-97902017000300015.
• [18] Mustafa WW, Fletcher J, Khoder M, Alany RG. Solid dispersions of gefitinib prepared by spray drying with improved mucoadhesive and drug dissolution properties. AAPS PharmSciTech. 2022;23(1):48. https://doi.org/10.1208/s12249-021-02187-4.
• [19] de Mohac LM, Raimi-Abraham B, Caruana R, Gaetano G, Licciardi M. Multicomponent solid dispersion a new generation of solid dispersion produced by spray-drying. J Drug Deliv Sci Technol. 2020;57:101750. https://doi.org/10.1016/j.jddst.2020.101750.
• [20] Gharsallaoui A, Roudaut G, Chambin O, Voilley A, Saurel R. Applications of spray-drying in microencapsulation of food ingredients: An overview. Food Res Int. 2007;40:1107–1121. https://doi.org/10.1016/j.foodres.2007.07.004.
• [21] Goula AM, Adamopoulos KG. Spray drying of tomato pulp in dehumidified air: I. The effect on product recovery. J Food Eng. 2005;66:25–34. https://doi.org/10.1016/j.jfoodeng.2004.02.029.
• [22] Bötschi S, Rajagopalan AK, Morari M, Mazzotti M. Feedback control for the size and shape evolution of needle-like crystals in suspension. IV. Modeling and control of dissolution. Cryst Growth Des. 2019;19:4029–4043. https://doi.org/10.1021/acs.cgd.9b00445
• [23] Kommavarapu P, Maruthapillai A, Palanisamy K, Koya RT. Effect of polymorphism and application of kinetic models for the evaluation of in vitro dissolution profiles of an eletriptan hydrobromide formulation. Dissolution Technol. 2015;22:30–37. https://doi.org/DOI:%2010.1023/A:1016020822093.
• [24] Adams E, Coomans D, Smeyers-Verbeke J, Massart DL. Application of linear mixed effects models to the evaluation of dissolution profiles. Int J Pharm. 2001;226:107–125. https://doi.org/10.1016/s0378-5173(01)00775-x.
• [25] Sathe PM, Tsong Y, Shah VP. In-vitro dissolution profile comparison: statistics and analysis, model dependent approach. Pharm Res. 1996;13(12):1799-1803. https://doi.org/10.1023/a:1016020822093.
• [26] Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123-133. https://doi.org/10.1016/s0928-0987(01)00095-1.
• [27] Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol. 1975;27(1):48-49. https://doi.org/10.1111/j.2042-7158.1975.tb09378.x.
• [28] Siswanto A, Fudholi A, Nugroho AK, Martono S. In vitro release modeling of aspirin floating tablets using Ddsolver. Indones J Pharm. 2015;26(2): 94-102. https://doi.org/10.14499/indonesianjpharm26iss2pp94
• [29] Murtaza G, Ahmad M, Khan S, Hussain I. Evaluation of cefixime-loaded chitosan microspheres: Analysis of dissolution data using DDSolver. Dissolution Technol. 2012;19:13–19. https://doi.org/10.14227/DT190212P13
• [30] Abali SO, Ekenna IC. Comparison of the use of kinetic model plots and DD Solver software to evaluate the drug release from griseofulvin tablets. J Drug Deliv Ther. 2022;12:5–13. https://doi.org/10.22270/jddt.v12i2-S.5402.
• [31] Elmubarak EH, Osman ZA, Abdelrahman M. Formulation and evaluation of solid dispersion tablets of furosemide using polyvinylpyrrolidone K-30. Int J Curr Pharm Res. 2021;13:43–50. https://doi.org/https:/dx.doi.org/10.22159/ijcpr.2021v13i2.41554
• [32] Raúl M-L, Sergio G-M, Marcela H. In vitro release studies of furosemide reference tablets: influence of agitation rate, USP apparatus, and dissolution media. ADMET DMPK. 2020;8:425–436. https://doi.org/10.5599/admet.801.
• [33] Fazaeli M, Emam-Djomeh Z, Ashtari AK, Omid M. Food and bioproducts processing effect of spray drying conditions and feed composition on the physical properties of black mulberry juice powder. Food Bioprod Process. 2012;90:667–675. https://doi.org/10.1016/j.fbp.2012.04.006
• [34] Osman AFA, Endut N. Spray drying of roselle-pineapple juice effects of inlet temperature and maltodextrin on the physical properties. 2nd International Conference on Environmental and Computer Science, ICECS 2009 2009:267–270. Https://doi.org/10.1109/ICECS.2009.91
• [35] Dressman JB, Krämer J. Pharmaceutical dissolution testing. Taylor & Francis; 2005.
• [36] U.S. Department of Health and Human Services. Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Forms. vol. 20857.
• [37] Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263-271. https://doi.org/10.1208/s12248-010-9185-1.
• [38] Huang W, Shi Y, Wang C, Yu K, Sun F, Li Y. Using spray-dried lactose monohydrate in wet granulation method for a low-dose oral formulation of a paliperidone derivative. Powder Technol. 2013;246:379–394. https://doi.org/10.1016/j.powtec.2013.05.042.
• [39] Phaechamud T, Koizumi T, Ritthidej GC. Chitosan citrate as film former: compatibility with water-soluble anionic dyes and drug dissolution from coated tablet. Int J Pharm. 2000;198(1):97-111. https://doi.org/10.1016/s0378-5173(99)00460-3.
• [40] Racz I, Dredan J, Antal I, Gondar E. Comparative evaluation of microcapsules prepared by fluidization atomization and melt coating process. Drug Dev Ind Pharm. 1997;23:583–587. https://doi.org/10.3109/03639049709149823.
• [41] Shingate PN, Dongre PP, Kannur DM. New method development for extraction and isolation of piperine from black pepper. Int J Pharm Sci Res. 2013;4:3165–3170. https://doi.org/10.13040/IJPSR.0975-8232.4(8).3165-70.
• [42] Saha KC, Seal HP, Noor MA. Isolation and characterization of piperine from the fruits of black pepper (Piper nigrum). J Bangladesh Agric Univ. 2013;11:11–16. https://doi.org/http:/dx.doi.org/10.3329/jbau.v11i1.18197.
• [43] Setyaningsih D, Santoso YA, Hartini YS, Murti YB, Hinrichs WLJ, Patramurti C. Isocratic high-performance liquid chromatography (HPLC) for simultaneous quantification of curcumin and piperine in a microparticle formulation containing Curcuma longa and Piper nigrum. Heliyon 2021;7:e06541. https://doi.org/10.1016/j.heliyon.2021.e06541.
• [44] Murti YB, Hartini YS, Hinrichs WLJ, Frijlink HW, Setyaningsih D. UV-VIS spectroscopy to enable determination of the dissolution behavior of solid dispersions containing curcumin and piperine. J Young Pharm. 2019;11:26–30. https://doi.org/10.5530/jyp.2019.11.6.