Handaratri, Anitarakhmi (2026) Proses Pembuatan Nanokurkumin Dengan Metode Solvent-Antisolvent Berbasis Teknologi Ultrasonik. Doctoral thesis, Institut Teknologi Sepuluh Nopember Surabaya.
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Abstract
Kurkumin merupakan senyawa bioaktif utama dari Curcuma longa yang memiliki berbagai aktivitas farmakologis, seperti antioksidan, antiinflamasi, dan antikanker. Namun, pemanfaatannya masih terbatas akibat kelarutan air yang sangat rendah (<10 μg/mL) dan bioavailabilitas yang buruk. Penelitian ini bertujuan untuk mengembangkan partikel kurkumin berukuran submikron hingga nano serta bentuk amorf menggunakan metode ultrasound-assisted liquid antisolvent (UALA), yang mengintegrasikan proses sonikasi selama pencampuran pelarut–antisolven untuk mempercepat nukleasi dan menghambat agregasi partikel.
Kurkumin dipreparasi menggunakan variabel diklorometana (DCM) dan juga aseton sebagai pelarut, air sebagai antisolven dengan variasi waktu sonikasi (0–40 menit) dan kecepatan pengadukan (800–1200 rpm) dan suhu pelarut 10ºC, 20ºC dan 30ºC. Optimasi proses dilakukan menggunakan Response Surface Methodology (RSM) dengan Box-Behnken Design (BBD). Karakterisasi meliputi Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Particle Size Analyzer (PSA), Differential Scanning Calorimetry (DSC), disolusi, IC50, dan analisa antioksidan. Kemudian dilakukan permodelan untuk kinetika pembentukan nanopartikel dan kinetika disolusi.
Hasil menunjukkan bahwa ukuran partikel kurkumin berhasil direduksi secara signifikan dari lebih dari 1000 nm menjadi kisaran 100–350 nm, dengan ukuran optimum mencapai 102.6 ± 3.1 nm pada kondisi sonikasi 30 menit. Reduksi ukuran ini disertai dengan penurunan derajat kristalinitas dari 58.7% menjadi sekitar 21% serta penurunan entalpi fusi dari 442.61 menjadi 28.57 kJ/mol, yang mengindikasikan terjadinya transformasi menuju fase semi-amorf hingga amorf. Karakterisasi XRD dan analisis termal mengonfirmasi perubahan struktur ini, sementara pengamatan SEM menunjukkan transformasi morfologi dari kristal memanjang menjadi partikel yang lebih tidak beraturan dan terfragmentasi.
Selain itu, formulasi berbasis kurkumin–lesitin menghasilkan struktur inti–kulit (core–shell) dengan efisiensi enkapsulasi sebesar 70–90% (w/w) dan kapasitas muat 10–15% (w/w), serta peningkatan sifat kebasahan dengan tegangan permukaan mencapai 27.9 ± 0.08 mN/m. Peningkatan sifat fisik ini berdampak langsung pada kinerja disolusi, di mana kurkumin hasil UALA menunjukkan peningkatan signifikan baik dalam laju maupun persen pelepasan. Disolusi mencapai hingga 94.36% dalam 60 menit, dibandingkan hanya 7.75% pada kurkumin mentah, serta mencapai sekitar 89.89% dalam 120 menit pada formulasi teroptimasi. Setelah penyimpanan selama 30 hari, performa disolusi tetap tinggi (84.20%), menunjukkan stabilitas yang baik.
Analisis kinetika disolusi menunjukkan bahwa model Kosmeyer-Peppas memberikan kecocokan terbaik dibandingkan model kinetika lainnya, yang mengindikasikan bahwa mekanisme pelepasan dikendalikan oleh kombinasi peningkatan luas permukaan dan disolusi cepat dari fase amorf. Selain itu, aktivitas antioksidan yang diuji menggunakan metode DPPH menunjukkan peningkatan signifikan, dengan penurunan nilai IC₅₀ dari sekitar 15 mg/mL pada kurkumin tanpa sonikasi menjadi kurang dari 1 mg/mL setelah perlakuan optimal, yang menunjukkan peningkatan potensi lebih dari 15 kali lipat.
Secara keseluruhan, metode UALA terbukti sebagai pendekatan satu langkah yang efektif, berkelanjutan, dan bebas carrier dalam menghasilkan nanokurkumin dengan sifat fisikokimia dan aktivitas bioaktif yang unggul. Peningkatan kinerja ini dicapai melalui kombinasi reduksi ukuran partikel, penurunan kristalinitas, peningkatan kebasahan, serta percepatan kinetika disolusi, sehingga metode ini berpotensi luas untuk aplikasi dalam bidang farmasi dan pangan fungsional.
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Curcumin is the principal bioactive compound of Curcuma longa and ex-hibits a wide range of pharmacological activities, including antioxidant, anti-inflammatory, and anticancer properties. However, its practical application is limited by its extremely low aqueous solubility (<10 μg/mL) and poor bioavailability. This study aimed to develop submicron- and nanosized amorphous curcumin particles using an ultrasound-assisted liquid antisolvent (UALA) process, which integrates ultrasonic irradiation during solvent–antisolvent mixing to accelerate nucleation while suppressing particle aggregation.
Curcumin was processed using dichloromethane (DCM) and acetone as solvents and water as the antisolvent. The process variables included sonication time (0–40 min), stirring speed (800–1200 rpm), and solvent temperature (10, 20, and 30°C). Process optimization was performed using Response Surface Methodol-ogy (RSM) based on a Box–Behnken Design (BBD). The resulting particles were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Elec-tron Microscopy (SEM), X-ray Diffraction (XRD), Particle Size Analysis (PSA), Differential Scanning Calorimetry (DSC), dissolution testing, IC₅₀ determination, and antioxidant activity analysis. Furthermore, kinetic models were developed to describe both nanoparticle formation and dissolution behavior.
The results demonstrated that the particle size of curcumin was significantly reduced from over 1000 nm to approximately 100–350 nm, with an optimum parti-cle size of 102.6 ± 3.1 nm achieved at a sonication time of 30 min. This size reduc-tion was accompanied by a decrease in the degree of crystallinity from 58.7% to approximately 21% and a reduction in the enthalpy of fusion from 442.61 to 28.57 kJ/mol, indicating a transformation from the crystalline state to a semi-amorphous or amorphous phase. XRD and thermal analyses confirmed these structural changes, while SEM observations revealed a morphological transformation from elongated crystalline structures to irregular and fragmented particles.
In addition, the curcumin–lecithin formulation produced a core–shell struc-ture with an encapsulation efficiency of 70–90% (w/w) and a loading capacity of 10–15% (w/w), together with enhanced wettability, as indicated by a surface ten-sion of 27.9 ± 0.08 mN/m. These improved physicochemical properties directly en-hanced the dissolution performance. UALA-processed curcumin exhibited substan-tial improvements in both dissolution rate and cumulative drug release, achieving up to 94.36% dissolution within 60 min compared with only 7.75% for raw curcumin, and approximately 89.89% dissolution after 120 min under the optimized condi-tions. After 30 days of storage, the dissolution performance remained high (84.20%), demonstrating good physical stability.
Dissolution kinetic analysis indicated that the Korsmeyer–Peppas model provided the best fit compared with other kinetic models, suggesting that the release mechanism was governed by the combined effects of increased surface area and the rapid dissolution of the amorphous phase. Furthermore, antioxidant activity evaluat-ed using the DPPH assay showed a remarkable improvement, with the IC₅₀ value decreasing from approximately 15 mg/mL for curcumin processed without soni-cation to less than 1 mg/mL after the optimized UALA treatment, representing more than a 15-fold increase in antioxidant potency.
Overall, the UALA process proved to be an effective, sustainable, one-step, and carrier-free approach for producing nanocurcumin with superior physicochemi-cal properties and enhanced bioactivity. These improvements were achieved through the synergistic effects of particle size reduction, decreased crystallinity, en-hanced wettability, and accelerated dissolution kinetics, highlighting the considera-ble potential of this method for pharmaceutical and functional food applications.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Kurkumin, bioavailabilitas, ultrasound-assisted liquid antisolvent, nanopartikel, solubilitas, morfologi ============================================================ curcumin, bioavailability, ultrasound-assisted liquid antisolventna-noparticle, solubility, morphology |
| Subjects: | T Technology > TP Chemical technology > TP1140 Polymers T Technology > TP Chemical technology > TP248.25.N35 Microencapsulation. T Technology > TP Chemical technology > TP370 Food processing and manufacture |
| Divisions: | Faculty of Industrial Technology and Systems Engineering (INDSYS) > Chemical Engineering > 24001-(S3) PhD Thesis |
| Depositing User: | Anitarakhmi Handaratri |
| Date Deposited: | 29 Jul 2026 02:04 |
| Last Modified: | 29 Jul 2026 02:04 |
| URI: | http://repository.its.ac.id/id/eprint/139216 |
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