Erizal Zaini

Aceclofenac (ACE) is a non-steroidal anti-inflammatory drug (NSAID) widely used for osteoarthritis and rheumatoid arthritis, yet its therapeutic performance is limited by poor aqueous solubility as a Biopharmaceutics Classification System (BCS) Class II drug. This study aimed to enhance the physicochemical and pharmacological properties of ACE by forming a multicomponent crystal (MC) with tromethamine (TRIS). The MC was produced via solvent-dropped grinding in a 1:1 molar ratio and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FTIR). DSC and PXRD results indicated the formation of a eutectic system with reduced crystallinity, while FTIR showed intermolecular hydrogen bonding, evidenced by the broad OH stretching band near 3000 cm⁻¹, without new covalent bond formation. Solubility increased 35.8-fold relative to pure ACE, and dissolution testing showed a markedly improved dissolution efficiency (DE₆₀) of 75.33 ± 1.57% compared with 49.10 ± 0.54% for ACE alone. In vivo anti-inflammatory assessment using a carrageenan-induced granuloma pouch model further demonstrated superior pharmacological activity of the MC, significantly reducing exudate volume (0.56 mL) and TNF-α levels (25.26 pg/mL) versus pure ACE (0.82 mL and 29.70 pg/mL). Overall, the ACE–TRIS multicomponent crystal effectively enhances solubility, dissolution, and anti-inflammatory efficacy, offering a promising approach for improving ACE’s therapeutic performance.

Piperine, classified as a Class II substance in the Biopharmaceutics Classification System (BCS), has poor solubility in water but high permeability. This research aims to improve the solubility and dissolution rate of piperine by adsorbing a multicomponent crystal (MCC) of piperine-nicotinamide onto mesoporous silica SBA-15. Tetraethyl orthosilicate (TEOS) was used as a silica precursor and Pluronic P123 as a pore-formation template to create SBA-15. Adsorption of the MCC was carried out by solvent evaporation with MCC:SBA-15 mass ratio (1:1). Solid state characterization was carried out by nitrogen adsorption-desorption isotherm, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM). Solubility tests were carried out for 24 hours and the dissolution rate profile was conducted for 60 minutes in distilled water. Dissolved piperine was determined using high performance liquid chromatography (HPLC) with methanol and distilled water as the mobile phase (75:25). The physical stability of MCC:SBA-15 was evaluated at various high relative humidities. The solid-state characterization results showed successful adsorption of the MCC in SBA-15 with a decrease in surface area, pore volume, and intensity of the X-ray diffraction peaks. The FT-IR spectrum of MCC:SBA-15 resembled that of SBA-15. The solubility test results showed 2.47-fold and 3.07-fold increases in solubility and dissolution rate compared to pure piperine, respectively. MCC:SBA-15 demonstrated high stability at 75% and 85% RH at 40◦C. In conclusion, adsorption of the MCC piperine-nicotinamide crystal in mesoporous silica SBA-15 can enhance the solubility and dissolution rate of piperine.

The Kaempferia galanga L rizhome (kencur) extract, known in traditional use as an appetite enhancer, was developed into chewable gummy preparations as a nutraceutical product. Due to the taste and odor of extract from natural plants caused less preferable to consume. Therefore the formulation of chewable gummy was addressed to overcome this problem. This study formulated gummy with a concentration of 2% galangal extract and gelatin as gelling agent with concentration variations of 10% (F1), 12.5% (F2), and 15% (F3). The evaluation of the physical properties of galangal rhizome extract chewable gummy included swelling ratio, syneresis, organoleptic, weight diversity, and texture profile analysis (TPA). In addition, a hedonic test was conducted to determine the level of panelist preference. The results revealed that the higher the gelatin concentration, the more significant the changes in the physical properties of gummies. An increase in gelatin plays a crucial role in forming a denser and more stable preparation structure. This impacts the texture regarding chewiness and increase the hardness. The result of TPA showed a significant differences (p<0.05) in the parameters of hardness, gumminess, and chewiness between the three formulations. The results of the hedonic test showed that F3 was the most preferred by the panelists. Based on these results, a gelatin concentration of 15% is recommended for the formulation of chewable gummy galangal rhizome extract.

Breast cancer remains a major health burden among women globally. While targeted therapies continue to evolve, affordable and effective alternatives are still needed. Niclosamide, an FDA-approved anthelmintic, shows promise for drug repurposing due to its anticancer activity, though its poor solubility and bioavailability limit clinical use. To address this, cocrystallization with saccharin, a GRAS-status coformer, was employed to enhance niclosamide’s physicochemical properties without altering its pharmacological effect. This study evaluates the cytotoxic effect of pure niclosamide and the niclosamide–saccharin cocrystal on T47D breast cancer cells, synthesized via the solvent drop grinding (SDG) method and assessed using the MTT assay with microplate spectrophotometric analysis. The results demonstrated that both pure niclosamide and its multicomponent crystal exhibited cytotoxic effects on T47D cells. Notably, the niclosamide–saccharin crystal showed a lower IC50 value (0.90 µg/mL) compared to that of pure niclosamide (1.39 µg/mL), indicating enhanced potency. A significant decrease in T47D cell viability was observed, suggesting that the multicomponent crystal formulation may augment the anticancer efficacy of niclosamide. In conclusion, the formation of a niclosamide–saccharin multicomponent crystal significantly enhances its cytotoxic activity against breast cancer cells in vitro. These findings underscore the potential of cocrystallization as a strategic formulation approach to improve the therapeutic performance of repurposed drugs in cancer treatment.

Objective: This study aimed to evaluate the cytotoxic activity of a niclosamide–caffeic acid multicomponent cocrystal against T47D breast cancer cells. Methods: The multicomponent cocrystal was prepared using the solvent-drop grinding method. Cytotoxic activity was assessed using the Microculture Tetrazolium Test (MTT) assay. Results: The results demonstrated that both niclosamide alone and the niclosamide–caffeic acid multicomponent cocrystal exhibited cytotoxic effects against T47D cells, with IC50 values of 2.92 μg/mL and 2.50 μg/mL, respectively. Microplate spectrophotometric analysis confirmed a concentration-dependent decrease in cell viability for both treatments. Notably, the niclosamide–caffeic acid multicomponent cocrystal displayed a more pronounced cytotoxic effect than niclosamide alone. Conclusions: These findings suggest that the formation of niclosamide–caffeic acid multicomponent crystals may enhance anticancer potential and warrant further investigation as a promising therapeutic approach for breast cancer treatment. Keywords: breast cancer, niclosamide, caffeic acid, multicomponent crystal, cytotoxicity, T47D cells, MTT assay.

P-Methoxycinnamic acid, a bioactive compound derived from the hydrolysis of ethyl p-methoxycinnamate found in the rhizome of Kaempferia galanga, possesses notable pharmacological activity, including analgesic, anti-inflammatory, and antidiabetic properties. However, its poor water solubility limits its effectiveness, necessitating high doses to achieve therapeutic levels. As a Biopharmaceutics Classification System (BCS) class II compound, it has low solubility but high permeability, making solubility and dissolution rate the main barriers to absorption. This study addresses these limitations by forming a multicomponent crystal with meglumine as a coformer to enhance its solubility and therapeutic potential. The multicomponent crystal was prepared in a 1:1 molar ratio using the solvent drop grinding method. Solid state characterization was performed using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). PXRD analysis revealed new diffraction peaks, indicating the formation of a distinct crystalline phase, while FT-IR spectra confirmed molecular interactions through wavenumber shifts. SEM analysis illustrated significant morphological changes in the multicomponent crystal compared to the pure constituent. Solubility of the multicomponent crystal showed a 3.4-fold increase, and dissolution studies demonstrated a 2.6-fold enhancement in dissolution efficiency compared to pure p-methoxycinnamic acid. These results highlight the successful formation of a p-methoxycinnamic acid-meglumine multicomponent crystal, classified as a salt. This approach not only improves solubility and dissolution efficiency but also provides a practical strategy for enhancing the formulation of poorly water-soluble drugs. These improvements may lead to better clinical performance and therapeutic outcomes, making it a valuable option in pharmaceutical development.

Objective: Ticagrelor (TICA), an antiplatelet agent used in cardiovascular treatment, is classified as a Class IV compound in the Biopharmaceutical Classification System, characterized by low solubility and low permeability, leading to poor bioavailability. This study aimed to enhance the solubility and dissolution rate of TICA through the formation of a multicomponent crystal with meglumine. Methods: Multicomponent crystals were prepared using the solvent drop grinding method. A binary phase diagram of ticagrelor and Meglumine (MEG) was constructed to determine the eutectic composition and temperature. Characterization was conducted using Differential Scanning Calorimetry, Fourier Transform Infrared Spectroscopy, Powder X-ray diffraction, and Scanning Electron Microscopy. Solubility tests and in vitro dissolution studies were performed to evaluate improvements in solubility and dissolution rate. Results: The binary phase diagram confirmed a simple eutectic mixture at a 4:6 molar ratio, with a eutectic temperature of 124.31 °C. The multicomponent crystal demonstrated 1.4 times higher solubility compared to intact ticagrelor. Dissolution studies showed significant improvements: 70.44% in 0.1 N HCl and 62.27% in CO₂-free distilled water within 60 min, compared to 40.39% and 31.38%, respectively, for intact TICA (P<0.05). Conclusion: The formation of TICA and MEG multicomponent crystals significantly enhanced solubility and dissolution rates, suggesting its potential to improve the bioavailability of TICA. This approach highlights the promise of multicomponent crystal technology in addressing the bioavailability challenges of Class IV drugs.

Ticagrelor is a triazolopyrimidine antiplatelet agent with poor water solubility. Ticagrelor was incorporated into mesoporous silica SBA15 in this study to evaluate its physical stability and improve its solubility and dissolution rate. TEOS was employed as a silica precursor and Pluronic P123 as a template to synthesize SBA-15. Ticagrelor was loaded into SBA-15 at a mass ratio of 1:1. Physicochemical characterization was conducted using nitrogen adsorption-desorption isotherm analysis, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Ticagrelor solubility and dissolution were tested using distilled water as the medium. To evaluate the physical stability, Ticagrelor-SBA-15 was stored in a climatic chamber at 75% RH and 40°C for a month and analyzed using PXRD. Physicochemical characterization indicated efficient adsorption of ticagrelor into the SBA-15 pores, resulting in an amorphous form of solid material. Meanwhile, solubility and dissolution rate testing showed respective increases of 1.33 times and 1.74 times with significant differences (p<0.05) while maintaining its physical stability after storage for one month. Based on this study, it can be concluded that the incorporation of mesoporous SBA-15 significantly enhances ticagrelor’s solubility and dissolution rate while maintaining stability.

Objective: To increase the dissolution rate of Ethyl p-methoxycinnamate (EPMC), which was isolated from Kaempferia galanga rhizome, this study aimed to prepare and characterize a Solid Dispersion (SD) system using the hydrophilic polymer Hydroxypropyl Methylcellulose (HPMC) K4M. Methods: EPMC was isolated from the rhizome of Kaempferia galanga and identified using a melting point instrument (Differential Scanning Calorimetry) and Thin Layer Chromatography (TLC). Three distinct EPMC and HPMC K4M ratios-1:1, 1:2, and 1:3 (w/w)-were freeze-dried to prepare the SD. Fourier Transform Infrared (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), and Differential Scanning Calorimetry (DSC) were used to characterize the SD. For 60 min, the dissolution test was carried out in distilled water free of CO2 and with an extra 0.1% Sodium Lauryl Sulfate (SLS). Results: The characterization of SD systems showed a decrease in the endothermic peak and melting point in the DSC analysis, decreased peak intensity in the PXRD patterns, unchanged chemical structure in FT-IR analysis, and pores formation on the surface in SEM analysis. A significant increase in dissolution rate (p<0.05) was observed, with a 3.63-fold improvement for the 1:3 SD (60.603±1.163%) compared to intact EPMC (16.684±1.352%). Conclusion: The SD of EPMC-HPMC K4M was successfully formed, and a higher dissolution rate was achieved than that of the intact EPMC.

Objective: Piperine, an active alkaloid in Piper nigrum and Piper retrofractum, is known for its anti-inflammatory, antioxidant, and bioavailability-enhancing properties. However, its low water solubility limits its therapeutic potential. Methods: This study addresses that limitation by enhancing piperine's solubility through forming multicomponent crystals using cinnamic acid as a coformer in a molar ratio of 4.5:5.5 via Liquid-Assisted Grinding (LAG). Various techniques, including X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FT-IR), and Scanning Electron Microscopy (SEM), were used to characterize these crystals. Solubility tests were conducted in CO2-free distilled water using sonication and analyzed with high-performance liquid chromatography (HPLC). Results: The DSC results revealed an endothermic peak at 79.91 °C, and XRD analysis showed no new peaks, indicating that the crystal structure of piperine remained unchanged. FT-IR analysis revealed hydrogen bond formation, and SEM showed smaller particle sizes in the modified crystals. Most importantly, the solubility of the multicomponent crystals increased 1.785-fold compared to intact piperine. Conclusion: These findings suggest that piperine-cinnamic acid multicomponent crystals, forming a eutectic mixture, significantly improve piperine’s solubility, with statistical analysis confirming the results (p<0.05).