Author(s): Muthia Fadhila, Sanezea Effendy, Siti Harina Siregar


DOI: 10.52711/0974-360X.2024.00347   

Address: Muthia Fadhila*, Sanezea Effendy, Siti Harina Siregar
Department of Pharmaceutics, School of Pharmaceutical Science Padang (STIFARM Padang), West Sumatera, Indonesia, 25147.
*Corresponding Author

Published In:   Volume - 17,      Issue - 5,     Year - 2024

With antiviral, antiproliferative, anti-inflammatory, and analgesic effects, usnic acid is an effective antimicrobial agent against human and plant diseases. The purpose of this study was to examine the physicochemical properties of usnic acid, a class II drug with high membrane permeability and poor solubility according to the Biopharmaceutical Classification System (BCS), by forming an inclusion complex with hydroxypropyl-ß-cyclodextrin, in order to improve its solubility and rate of dissolution. In order to compare the two physical mixtures, this study used the co-grinding process with a molar ratio of 1:1 and 1:2. Physicochemical characteristics, solubility tests, and dissolution tests were used to evaluate the inclusion complexation and physical mixes. Differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR), and X-ray diffraction (XRD) were used to evaluate the physicochemical characteristics of the samples. The dissolving experiments were conducted using phosphate buffer at pH 7.4, whereas the solubility tests were conducted with CO2-free aquadest. Solubility tests with 1:1 inclusion complexes showed a 9-fold increase and 1:2 complexes a 10-fold increase over pure usnic acid. A dissolving percentage of 13.35% was achieved in the 60th minute, surpassing the dissolution percentage of pure usnic acid (which is 3.05% in the dissolution test), indicating a greater dissolution rate compared to other formulae in the 1:2 mol inclusion complexation.

Cite this article:
Muthia Fadhila, Sanezea Effendy, Siti Harina Siregar. Inclusion Complexation of Usnic Acid - Hydroxypropyl-β-cyclodextrin: Physicochemical Characterization and Dissolution Rate Studies. Research Journal of Pharmacy and Technology. 2024; 17(5):2206-2. doi: 10.52711/0974-360X.2024.00347

Muthia Fadhila, Sanezea Effendy, Siti Harina Siregar. Inclusion Complexation of Usnic Acid - Hydroxypropyl-β-cyclodextrin: Physicochemical Characterization and Dissolution Rate Studies. Research Journal of Pharmacy and Technology. 2024; 17(5):2206-2. doi: 10.52711/0974-360X.2024.00347   Available on:

1.    Müller, K. Pharmaceutically relevant metabolites from lichens. Appl. Microbiol. Biotechnol. 2001; 56:  9–16.
2.    Ingólfsdóttr, K. Usnic acid. Phytochemistry61, 729–736 (2002).
3.    Cansaran, D., Kahya, D., Yurdakulol, E. and Atakol, O. Identification and quantitation of usnic acid from the lichen Usnea species of anatolia and antimicrobial activity. Zeitschrift fur Naturforsch.  Sect. C J. Biosci. 2006; 61: 773–776.
4.    Safak, B. et al. In Vitro Anti-Helicobacter pylori Activity of Usnic Acid. Phyther. Res.23, 955–957 (2009).
5.    Lira, M. C. B. et al. In vitrouptake and antimycobacterial activity of liposomal usnic acid formulation. J. Liposome Res. 2009; 19: 49–58.
6.    Ribeiro-Costa, R. M. et al. In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres. J. Microencapsul. 2004; 21: 371–384.
7.    Takai, M., Uehara, L. Y. and Beisler, J. A. Usnic Acid Derivatives as Potential Antineoplastic Agents. J. Med. Chem. 1979; 22: 1380–1384.
8.    Choudhary, H., Yadav, B., Patel, P., Das, P. and Pillai, S. Formulation and evaluation of ramipril fast dissolving tablet using solid dispersion. Res. J. Pharm. Technol. 2019; 12: 3764–3772.
9.    Samir, A., El-Megrab, N., Fattah, H. A. and Barakat, W. Solubility Enhancement of Poorly Water Soluble Drug by Solid Dispersion Technique. Asian J. Res. Chem. 2012; 5: 483–491.
10.    Mahaparale, P. R. and Thorat, V. P. Enhancement of solubility of leflunomide with β-cyclodextrin inclusion complexation. Res. J. Pharm. Technol. 2021; 14: 809–812.
11.    Sujani, S., Babu, R. H. and Reddy, K. R. Preparation of meloxicam spherical agglomerates to improve dissolution rate. Asian J. Pharm. Res. 2012; 2: 32–36.
12.    Kumara Swamy, S. and Alli, R. Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery. Asian J. Pharm. Technol. 2021; 11: 1–7.
13.    Mandake, G. R., Shinde, S. S., Patil, O. A. and Nitalikar, M. M. Dissolution enhancement of Telmisartan by spray drying technique. Asian J. Pharm. Technol. 2018; 8: 264–269.
14.    Girishchandra, R. et al. Modification of Dissolution Profile of Rivaroxaban by spray Drying. Asian J. Pharm. Technol. 2018; 8: 203–210.
15.    Yadav, V. B., Yadav, A. V, Polshettiwar, S. A. and Wani, M. S. Improved Solubility and Dissolution Behavior of Norfloxacin by Crystal Modification. Res. J. Pharm. Technol. 2008; 1: 29–32.
16.    Jawahar, N. et al. Polymorphism : A Dissolution Rate Enhancement Technique of Nitrendipine. Res. J. Pharm. Tech. 2008; 1: 285–286.
17.    Lira, M. C. B. et al. Inclusion complex of usnic acid with β-cyclodextrin: Characterization and nanoencapsulation into liposomes. J. Incl. Phenom. Macrocycl. Chem. 2009; 64: 215–224.
18.    Fadhila, M., Umar, S. and Zaini, E. Pembentukan Kokristal Asam Usnat – N-Methyl-DGlucamine dengan Metode Penguapan Pelarut dan Pengaruhnya terhadap Penurunan Interleukin-8 pada Tikus Inflamasi. J. Sains Farm. Klin. 2020; 7: 23.
19.    Kristmundsdóttir, T., Jónsdóttir, E., Ögmundsdóttir, H. M. and Ingólfsdóttir, K. Solubilization of poorly soluble lichen metabolites for biological testing on cell lines. Eur. J. Pharm. Sci. 2005; 24: 539–543.
20.    Bekers, O., Uijtendaal, E. V., Beijnen, J. H., Bult, A. and Underberg, W. J. M. Cyclodextrins in the Pharmaceutical Field. 1991; 17: 1503–1549.
21.    Setyawan, Dwi dan Putri, D. Strategi Peningkatan Kelarutan Bahan Aktif Farmasi. 2019; 80: 126–31.
22.    Nikolić, V. et al. Inclusion complexes with cyclodextrin and usnic acid. J. Incl. Phenom. Macrocycl. Chem. 2013; 76: 173–182.
23.    Fadhila, M., Halim, A. and Assyifa. Characterization and Dissolution Rate Studies of Inclusion Complex of Glibenclamide and Hydroxypropyl-Β-Cyclodextrin Using Co-Grinding Method. Int. J. Appl. Pharm. 2022; 14: 251–255.
24.    Rathi, S., Patel, D. and Shah, S. Physicochemical characterization and in-vitro dissolution behavior of artemether and lumefantrine: Hydroxypropyl-Β-cyclodextrin inclusion complex. Res. J. Pharm. Technol. 2020; 13: 1137–1141.
25.    Fitriani, L., Afriyanti, I., Afriyani, Ismed, F. and Zaini, E. Solid dispersion of usnic acid–HPMC 2910 prepared by spray drying and freeze drying techniques. Orient. J. Chem. 2018; 34: 2083–2088.
26.    Zaini, E., Nisak, R. K., Utami, R. D., Fitriani, L. and Ismed, F. Effect of milling on physicochemical properties of usnic acid isolated from usnea sp. Orient. J. Chem. 2017; 33: 3031–3036.
27.    Budiman, A., Megantara, S. and Apriliani, A. Solid dosage form development of glibenclamide-aspartame cocrystal using the solvent evaporation method to increase the solubility of glibenclamide. Int. J. Appl. Pharm. 2019; 11: 150–154.
28.    Fitriani, L., Rismawati, E., Umar, S. and Zaini, E. Solid dispersion of usnic acid-PVP K30 and evaluation of antioxidant activity. Rasayan J. Chem. 2018; 11: 1643–1648.
29.    Qu, C. et al. Preparation and evaluation of wet-milled usnic acid nanocrystal suspension for better bioaffinity. Drug Dev. Ind. Pharm. 2018; 44: 707–712.
30.    Schultheiss, N. and Newman, A. Pharmaceutical cocrystals and their physicochemical properties. Cryst. Growth Des. 2009; 9: 2950–2967.
31.    Dachriyanus. Analisis Struktur Senyawa Organik Secara Spektroskopi. (LPTIK Universitas Andalas, 2004).
32.    Trask, A. V., Haynes, D. A., Motherwell, W. D. S. and Jones, W. Screening for crystalline salts via mechanochemistry. Chem. Commun. 2006; 51–53 doi:10.1039/b512626f.
33.    Trask, A. V., Motherwell, W. D. S. and Jones, W. Physical stability enhancement of theophylline via cocrystallization. Int. J. Pharm. 2006; 320: 114–123.
34.    Elfiyani, R., Amalia, A. and Integra, A. The Influence of B-Cyclodextrin Concentrations as Ligands on Inclusion Complexes To Increase the Solubility of Ibuprofen. J. Pharm. Sci. Community. 2020; 17: 8–19.
35.    Putra, O. D. D., Yonemochi, E. and Uekusa, H. Isostructural Multicomponent Gliclazide Crystals with Improved Solubility. Cryst. Growth Des. 2016; 16: 6568–6573.
36.    O’Neil. The Merck Index 13th edition. 2001.
37.    Del Valle, E. M. M. Cyclodextrins and their uses: A review. Process Biochem. 2004; 39: 1033–1046.
38.    Loftsson, T. and Duchêne, D. Cyclodextrins and their pharmaceutical applications. Int. J. Pharm. 2007; 329: 1–11.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available