The dissolution of p-methoxycinnamic acid-β-cyclodextrin inclusion complex produced with microwave irradiation
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Background: p-methoxycinnamic acid (pMCA) is an ethyl p-methoxycinnamic derivative, which is the largest active ingredient in the rhizome of the kencur (Kaempferia galanga L) plant. Several studies reported that the compound has anti-inflammatory activity but has low solubility in water. The formation of a pMCA-β-cyclodextrin (βCD) inclusion complex with a molar ratio of 1:1 can increase its solubility. The formation of inclusion complexes with conventional methods requires a long time and the yield value is not optimal.
Objective: This study aims to evaluate the dissolution of the pMCA-βCD inclusion complex produced using the microwave irradiation method.
Methods: The product was manufactured with chloroform solvent and a power of 400 watts (power 80%). It was then evaluated using the Differential Thermal Analysis (DTA) every 2 minutes until the 8th minute. The reaction was complete after 4 minutes of treatment with a yield of 96.5%. The obtained inclusion complexes were evaluated using DTA, FTIR, and PXRD. Subsequently, a dissolution test was carried out using a type 2 apparatus in distilled water medium of pH 6.8±0.05 at 37±0.5°C.
Results: The results showed that there was a change in the melting temperature profile, infrared spectra, and crystallinity of the product. An 89.18% dissolution was also obtained within 60 minutes, which was twice that of pMCA compounds.
Conclusion: From the results of the study, it can be concluded that the formation of pMCA-βCD inclusion complexes using the microwave irradiation method is capable of providing high-yield values in a short time.
Sharma P. Cinnamic acid derivatives: A new chapter of various pharmacological activities. J Chem Pharm Res. 2011;3:403–23.
Ekowati J, Diyah NW. Antinociceptive activity and in silico test against cyclooxygenase from p-methoxycinnamic acid and m-methoxycinnamic acid. BIKF. 2013;2:33–40.
Guzman JD. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity. Molecules, 2014;19:19292–349. DOI: https://doi.org/10.3390/molecules191219292
Isadiartuti D, Rosita N, Syahrani A, et al. pH Adjustment and Inclusion Complex Formation With Hydroxypropyl-β-Cyclodextrin To Increase p-Methoxycinnamic Acid Solubility. J Chem Technol Metall. 2022;57:723-9.
Cheirsilp B, Rakmai J. Inclusion complex formation of cyclodextrin with its guest and their applications. Biol Eng Med, 2016;2:1-6. DOI: https://doi.org/10.15761/BEM.1000108
Loftsson T, Brewster ME. Cyclodextrins as a Functional Excipients: Methods to Enhance Complexation Efficiency, J Pharm Sci. 2012;101:3019-32. DOI: https://doi.org/10.1002/jps.23077
Alshehri S, Imam SS, Altamimi MA, et al. Host-guest complex of β-cyclodextrin and pluronic F127 with Luteolin: Physicochemical characterization, anti-oxidant activity and molecular modeling studies. J Drug Deliv Sci Technol [Internet]. 2020;55:101356. DOI: https://doi.org/10.1016/j.jddst.2019.101356
Bekers O, Uijtendaal EV, Beijnen JH, et al. Cyclodextrins in the pharmaceutical Field. Drug Dev Ind Pharm. 1991;17:1503–49. DOI: https://doi.org/10.3109/03639049109026630
Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical formulations I: Structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today [Internet]. 2016;21:356–62. DOI: https://doi.org/10.1016/j.drudis.2015.11.017
Isadiartuti D, Martodiharjo S. The formation of inclusion complex of phenobarbital with hydroxypropyl-β-cyclodextrin. MFI. 2005;16:28–37.
Kulkarni AS, Dias RJ, Ghorpade VS, Mali KK. Freeze-dried multicomponent inclusion complexes of curcumin for enhancement of solubility and anti-inflammatory activity. Trop J Nat Prod Res. 2020;4:887–94.
Borba PAA, Pinotti M, Andrade GRS, et al. The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and β-cyclodextrins. Carbohydr Polym. 2015;133:373–83. DOI: https://doi.org/10.1016/j.carbpol.2015.06.098
Isadiartuti D, Martodiharjo S. The thermodynamics of inclusion complex of phenobarbital with hydroxypropyl-β-cyclodextrin. MFI. 2007;18:57–62.
Ekowati J, Rudyanto M, Sasaki S, et al. Structure Modification of Ethyl p-methoxycinnamate Isolated from Kaempferia galanga Linn. and Citotoxicity Assay of The Products on WiDr Cells. ISCC. 2010;1:12. DOI: https://doi.org/10.14499/indonesianjcanchemoprev1iss1pp12-18
Isadiartuti D, Rosita N, Ekowati J, et al. The thermodynamic study of p-methoxycinnamic acid inclusion complex formation, using β-cyclodextrin and hydroxypropyl- β-cyclodextrin. J Basic Clin Physiol Pharmacol. 2021;32:663–7. DOI: https://doi.org/10.1515/jbcpp-2021-0008
Patil PH, Belgamwar VS, Patil PR, Surana SJ. Solubility Enhancement of Raloxifene Using Inclusion Complexes and Cogrinding Method. J Pharm. 2013;2013:1–9. DOI: https://doi.org/10.1155/2013/527380
Das S, Maharana J, Mohanty S, Subuddhi U. Spectroscopic and computational insights into theophylline/β-cyclodextrin complexation: inclusion accomplished by diverse methods. J Microencapsul [Internet]. 2018;35:667–79. DOI: https://doi.org/10.1080/02652048.2019.1572239
Kappe CO, Dallinger D. The impact of microwave synthesis on drug discovery. Nat Rev Drug Discov. 2006;5:51–63. DOI: https://doi.org/10.1038/nrd1926
Das S, Subuddhi U. Studies on the complexation of diclofenac sodium with β-cyclodextrin: Influence of method of preparation. J Mol Struct [Internet]. 2015;1099:482–9. DOI: https://doi.org/10.1016/j.molstruc.2015.07.001
Kaur KP, Upadhyaya T, Palandoken M, Gocen C. Ultrathin dual-layer triple-band flexible microwave metamaterial absorber for energy harvesting applications. Int J RF Microw Comput Eng. 2019;29:1–7. DOI: https://doi.org/10.1002/mmce.21646
Mura P. Analytical techniques for characterization of cyclodextrin complexes in the solid state: A review. J Pharm Biomed Anal [Internet]. 2015;113:226–38. DOI: https://doi.org/10.1016/j.jpba.2015.01.058
Yaqin IN, Ekowati J, Nofianti KA, Suzana S. Utilization of Microwaves Irradiation on Synthesis of Methyl ortho-Methoxycinnamate. J Sains Farm Klin. 2021;8:157. DOI: https://doi.org/10.25077/jsfk.8.2.157-163.2021
Ghosh A, Biswas S, Ghosh T. Preparation and evaluation of silymarin β-cyclodextrin molecular inclusion complexes. J Young Pharm. 2011;3:205–10. DOI: https://doi.org/10.4103/0975-1483.83759
Rachmawati H, Edityaningrum CA, Mauludin R. Molecular inclusion complex of curcumin-β-cyclodextrin nanoparticle to enhance Curcumin skin permeability from hydrophilic matrix gel. AAPS PharmSciTech. 2013;14:1303–12. DOI: https://doi.org/10.1208/s12249-013-0023-5
Gao S, Bie C, Ji Q, et al. Preparation and characterization of cyanazine-hydroxypropyl-β-cyclodextrin inclusion complex. RSC Adv. 2019;9:26109–15. DOI: https://doi.org/10.1039/C9RA04448E
Copyright (c) 2023 the Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.