Acemetacin 60mg capsules

Developing new and versatile platinum(IV) complexes that incorporate bioactive moieties is a rapidly evolving research strategy for cancer drug discovery. In this study, six platinum(IV) complexes (1–6) that are mono-substituted in the axial position with a non-steroidal anti-inflammatory molecule, naproxen or acemetacin, were synthesised. A combination of spectroscopic and spectrometric techniques confirmed the composition and homogeneity of 1–6. The antitumour potential of the resultant complexes was assessed on multiple cell lines and proved to be significantly improved compared with cisplatin, oxaliplatin and carboplatin. The platinum(IV) derivatives conjugated with acemetacin (5 and 6) were determined to be the most biologically potent, demonstrating GI50 values ranging between 0.22 and 250 nM. Remarkably, in the Du145 prostate cell line, 6 elicited a GI50 value of 0.22 nM, which is 5450-fold more potent than cisplatin. A progressive decrease in reactive oxygen species and mitochondrial activity was observed for 1–6 in the HT29 colon cell line, up to 72 h. The inhibition of the cyclooxygenase-2 enzyme was also demonstrated by the complexes, confirming that these platinum(IV) complexes may reduce COX-2-dependent inflammation and cancer cell resistance to chemotherapy.

Abstract licence: CC BY 4.0

Amorphization is widely used as an effective method of increasing the solubility of insoluble drugs. However, some amorphous drugs exhibit a much lower dissolution rate than their corresponding crystalline form due to their gelation. In this study, we reported the gels formed from amorphous acemetacin (ACM) for the first time. Gelation was promoted at conditions of lower pH, higher temperature and lower ionic strength. Solid-state characterizations suggested that ACM gels may be formed by recrystallization. This mechanism provides a new direction in facilitating the elimination of gelation for amorphous drugs. Moreover, it also provides the basis for the development of sustained-release formulations using the gelation properties.

Abstract licence: CC BY 4.0

AbstractThe non-steroidal anti-inflammatory medication acemetacin was assessed via two straightforward green spectrofluorimetric techniques. The quenching-dependent derivatizing spectrofluorimetric reactions are the master point of this study. Acriflavine-based method (Method I) depends on forming an ion association complex between acriflavine and the drug in a ratio of 1:1, decreasing the former's fluorescence intensity. Acriflavine or Ag NP's intensity-related quenching action goes linearly with the acemetacin concentration in the 2.0–20.0 µg/mL and 1.0–16.0 µg/mL ranges, respectively. The second quenching mechanism depends on using the silver nanoparticles (Ag NP's) as a fluorescence probe (Method II); Ag NP's were prepared from reducing silver nitrate using sodium borohydride. Both methods could be applied to determine pure and pharmaceutical dosage forms of acemetacin. The methods proved valid according to the international conference on harmonization (ICH) guidelines. In addition to this, this work has been estimated under green criteria assessment tools. There is no significant difference between the proposed and the comparison methods after the statistical interpretation.

Abstract licence: CC BY 4.0

Acemetacin (ACM) is a new non-steroidal anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. However, the poor water solubility and gastrointestinal side effects limit its use. Recently, the co-amorphous (CAM) strategy has attracted great interest to improve solubility for poorly water-soluble drugs, and basic amino acids have the potential to protect the gastrointestinal tract. In order to develop a highly efficient and low-toxic ACM formulation, we prepared ACM CAM systems, with basic amino acids (lysine, arginine, and histidine) as co-formers, using a cryo-milling method. The solid-state behaviors of the ACM CAM systems were characterized by polarizing light microscopy, differential scanning calorimetry, and powder X-ray diffraction. Fourier transform infrared spectroscopy and molecular docking were carried out to understand the formation mechanism. Moreover, the gastro-protective effects of ACM CAM systems were evaluated in a rat gastric ulcer model. The results demonstrated that the CAM systems improved the dissolution rates of ACM compared with the neat amorphous counterpart. Furthermore, ACM CAM systems are significantly effective in mitigating the ACM-induced gastric ulcer in rats, and the ulcer inhibition rates were almost 90%. More importantly, this study provided a useful method for mitigating drug-induced gastrointestinal damage and broadened the applications of drug–amino acid CAM systems.

Abstract licence: CC BY 4.0

Acemetacin (ACM) is classified as a non-steroidal anti-inflammatory drug (NSAID). It is an indomethacin glycolic ester that is transformed into indomethacin in vivo. The analgesic, antipyretic, and anti-inflammatory properties of the ACM are attributed to its prostaglandin inhibitory action. Acemetacin belongs to biopharmaceutical classification system (BCS) class II drugs, which are characterized by having high permeability but poor aqueous solubility. The purpose of this study was to develop acemetacin nanoparticles (ACM NPs) for enhanced solubility and rate of dissolution. The solvent-anti-solvent approach was used to formulate the nanoparticles. Two stabilizers were used to prepare ACM NPs (sodium deoxycholate (SDC) and Soluplus®). Design Expert® software was used to create the experiments utilizing a computer-based approach. The Box-Behnken design was used for this purpose in order to investigate the effect of different formulation variables on particle size and polydispersity index (PDI) of ACM NPs. Using Soluplus® as a stabilizer, the chosen formula F22 has desirability value 0.701, and its particle size and PDI values were 59.69 nm and 0.1847 respectively. The saturated solubility of ACM in the generated nanoparticles was approximately ten times greater than that of the naked drug (25.01 μg/ml vs. 2.43 μg/ml), and a 100% dissolution was accomplished in 90 minutes compared to the naked ACM, which only gave 47% in this time frame. In conclusion, this is the first time reporting the preparation of ACM nanosuspension, and turning ACM into polymeric nanoparticles is an effective method to increase the solubility and rate of dissolution of the drug, readying it for incorporation into a dosage form requiring such properties.

Abstract licence: CC BY 4.0

Acemetacin is the carboxymethyl ester of indomethacin and is a pro-drug precursor compound, in other words, a prodrug. The pharmacologically active metabolite of acemetacin is also indomethacin. Acemetacin exerts its potent non-steroidal anti-inflammatory effects in the body as indomethacin. It is known that acemetacin is not only a prodrug of indomethacin, but also an agent with gastric protective mechanisms, possibly involving a reduction in leukocyte adhesion, and that acemetacin exerts gastric protective effects by exhibiting less efficacy on the COX-1 enzyme in the gastric mucosa compared to direct indomethacin use. It is clear that acemetacin is a valuable NSAID for acute and chronic pain. Keywords: Acemetacin, indomethacin, non-steroidal anti-inflammatory drugs.

Abstract licence: CC BY-NC 4.0

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, Smix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM.

Abstract licence: CC BY 4.0

Polar and non-polar solvents like water (ε = 78.5), ethanol (ε = 24.852), acetone (ε = 20.493) and diethyl ether (ε = 4.24) were employed to study the solubility of acemetacin, which is a non-steroidal anti-inflammatory drug (NSAID) through quantum density functional theoretical studies using B3LYP/6-31G(d) level. In present study, acemetacin was optimized in the gaseous phase and further explored in the solution phase environments. The characteristic parameters of acemetacin such as bond lengths, bond angles, total energy, dipole moment, thermal energies, specific heat, entropy and zero point vibrational energy in gaseous and solution phases were computed. The energy difference between most stable [acemetacin in water (AMN-W)] and the least stable structure [acemetacin in diethyl ether (AMN-D)] was found to be 3.76 Kcal/mol. The zero point vibrational energy of acemetacin in gas phase is found to be 225.05 Kcal/mol. The fundamental vibrational frequency analysis of acemetacin has been done by using B3LYP/6-31G(d) level and compared with the harmonic vibrational frequencies. The HOMO-LUMO analysis of acemetacin has also been investigated. The molecular electrostatic potential (MEP) map was applied to study the distribution of charge density and the location of the chemical reactivity of acemetacin.

Abstract licence: CC BY 4.0