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Pharmaceutics Jun 2024The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative...
The demonstration of bioequivalence proposed in the European Medicines Agency's (EMA's) draft guideline for topical products with the same qualitative and quantitative composition requires the confirmation of the internal structure equivalence. The impact of the shelf-life on the parameters proposed for internal structure comparison has not been studied. The objectives of this work were: (1) to quantify the effect of the time since manufacturing on the mean value and variability of the parameters proposed by the EMA to characterize the internal structure and performance of topical formulations of a complex topical formulation, and (2) to evaluate the impact of these changes on the assessment of the microstructure equivalence. A total of 5 batches of a topical emulgel containing 1% diclofenac diethylamine were evaluated 5, 14, and 23 months after manufacture. The zero-shear viscosity (η), viscosity at 100 s (η), yield stress (σ), elastic (G') and viscous (G″) moduli, internal phase droplet size and in vitro release of the active ingredient were characterized. While no change in variability over time was detected, the mean value of all the parameters changed, especially the droplet size and in vitro release. Thus, combining data from batches of different manufacturing dates may compromise the determination of bioequivalence. The results confirm that to assess the microstructural similarity of complex formulations (such as emulgel), the 90% confidence interval limit for the mean difference in rheological and in vitro release parameters should be 20% and 25%, respectively.
PubMed: 38931871
DOI: 10.3390/pharmaceutics16060749 -
Plants (Basel, Switzerland) Jun 2024The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into...
The development of new drugs derived from plant sources is of significant interest in modern pharmacy. One of the promising plant sources for introduction into pharmaceuticals is (L.) Sch. Bip., also known as (Merat.) M. This plant has been shown to possess various biological activities, including anti-inflammatory, antimicrobial, and antimycotic activities, among others. However, a review of the current literature reveals a paucity of studies investigating the chemical composition of the herb (L.) Sch. Bip. This study presents the development of a method for obtaining an extract of the herb (L.) Sch. Bip. enriched with flavonoids, harvested before flowering and butonization. This study focused on determining the optimal conditions for extraction, including the concentration of the extractant (ethanol), extraction time, raw material/extractant ratio, extraction frequency, complexation reaction time, amount of aluminum chloride solution, and amount of diluted acetic acid. The results indicate that herbs harvested during this specific period exhibited a higher flavonoid content compared to those collected during butonization and flowering. Moreover, this study demonstrated that the flavonoid content could exceed 7% mg REq/100 g D.W. through a one-hour extraction process. Furthermore, the flavonoid content was found to be 7.65 ± 0.03 mg REq/100 g D.W. following a three-minute ultrasound-assisted extraction process, followed by thermal extraction. A qualitative analysis identified a variety of phenolic compounds in the extract, such as chlorogenic acid, 5--p-coumaroylquinic acid, 1--p-coumaroylquinic acid, luteolin-7-glucoside, quercetin-3-glucoside, luteolin-7-rutinoside, 3,5--dicaffeoylquinic acid, quercetin-3--malonylglucoside, apigenin-7-glucoside, luteolin-3-malonylglucoside, cynarin, rhamnetin-3-(-dimethyl rhamnosyl glucosylglucoside), and luteolin. Moreover, this study demonstrated the antimicrobial, anti-inflammatory, anticoagulant, anti-aggregation, and antioxidant activities of the aqueous alcoholic extract from herb (ETIH) against pathogens such as , , and . Additionally, the extract exhibited comparable anti-inflammatory effects on diclofenac sodium. These findings contribute to the understanding of the potential pharmacological applications of the developed herb extract.
PubMed: 38931061
DOI: 10.3390/plants13121629 -
Molecules (Basel, Switzerland) Jun 2024An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical...
An RP-HPLC method with a UV detector was developed for the simultaneous quantification of diclofenac diethylamine, methyl salicylate, and capsaicin in a pharmaceutical formulation and rabbit skin samples. The separation was achieved using a Thermo Scientific ACCLAIM 120 C column (Waltham, MA, USA, 4.6 mm × 150 mm, 5 µm). The optimized elution phase consisted of deionized water adjusted to pH = 3 using phosphoric acid mixed with acetonitrile in a 35:65% (/) ratio with isocratic elution. The flow rate was set at 0.7 mL/min, and the detection was performed at 205 nm and 25 °C. The method exhibits good linearity for capsaicin (0.05-70.0 µg/mL), methyl salicylate (0.05-100.0 µg/mL), and diclofenac diethylamine (0.05-100.0 µg/mL), with low LOD values (0.0249, 0.0271, and 0.0038 for capsaicin, methyl salicylate, and diclofenac diethylamine, respectively). The RSD% values were below 3.0%, indicating good precision. The overall greenness score of the method was 0.61, reflecting its environmentally friendly nature. The developed RP-HPLC method was successfully applied to analyze Omni Hot Gel pharmaceutical formulation and rabbit skin permeation samples.
Topics: Capsaicin; Diclofenac; Chromatography, High Pressure Liquid; Salicylates; Skin; Animals; Rabbits; Chromatography, Reverse-Phase; Diethylamines
PubMed: 38930798
DOI: 10.3390/molecules29122732 -
Antioxidants (Basel, Switzerland) May 2024The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and...
Preliminary Investigation of subsp. : LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2.
The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the subsp. extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC value for the extract was determined to be 19.44 ± 0.04 μg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the extract, with an LC value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin's potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds.
PubMed: 38929093
DOI: 10.3390/antiox13060654 -
Journal of Endodontics Jun 2024This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on...
Influence of Diclofenac Potassium versus Prednisolone on Post-endodontic Pain and Pulpal Interleukin-8 expression in Symptomatic Irreversible Pulpitis Cases: A Randomized Placebo-Controlled Trial.
AIM
This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on post-endodontic pain and pulpal interleukin (IL)-8 expression in patients with irreversible pulpitis.
METHODS
Thirty-six patients undergoing conventional endodontic treatment were assigned into one of three groups (n= 12). Pulpal blood samples were taken after access cavity preparation and stored until they were analyzed using ELISA for quantification of IL-8. Post-endodontic pain was scored using the visual analogue scale. Outcome data were statistically analyzed using one-way ANOVA, Kruskal-Wallis, Friedman's, Dunn's, Chi-square, and Fisher's exact tests and Spearman's correlation coefficient. The significance level (α) was set at 0.05.
RESULTS
Apart from pre-operative pain scores, all groups had similar baseline characteristics (P > .05). Immediate post-endodontic pain scores had a significant difference between all groups (P < .05) where placebo group showed the highest score. There was no significant difference between all groups at 6 and 12 hours post-operatively (P > .05). Furthermore, there was no significant difference in the incidence of post-endodontic pain and in mean IL-8 levels between the three groups (P > .05).
CONCLUSIONS
The only impact the premedications had was on the immediate post-endodontic pain intensity, and they had no influence on the later time points, incidence of post-endodontic pain or pulpal IL-8 levels.
PubMed: 38925367
DOI: 10.1016/j.joen.2024.05.019 -
The Journal of Biological Chemistry Jun 2024Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of...
Transthyretin (TTR) is a homotetrameric protein involved in the transport of thyroxine. More than 150 different mutations have been described in the TTR gene, several of them associated with familial amyloid cardiomyopathy (FAC). Recently, our group described a new variant of TTR in Brazil, namely A39D-TTR, which causes a severe cardiac condition. Position 39 is in the AB loop, a region of the protein that is located within the thyroxine-binding channels and is involved in tetramer formation. In the present study we solved the structure and characterize the thermodynamic stability of this new variant of TTR using urea and high hydrostatic pressure (HHP). Interestingly, during the process of purification, A39D-TTR turned out to be a dimer and not a tetramer, a variation that might be explained by the close contact of the four aspartic acids at position 39, where they face each other inside the thyroxine channel. In the presence of sub-denaturing concentrations of urea, bis-ANS binding and dynamic light scattering revealed A39D-TTR in the form of a molten-globule dimer. Co-expression of A39D and WT isoforms in the same bacterial cell did not produce heterodimers or heterotetramers, suggesting that somehow a negative charge at the AB loop precludes tetramer formation. A39D-TTR proved to be highly amyloidogenic, even at mildly acidic pH values where WT-TTR does not aggregate. Interestingly, despite being a dimer, aggregation of A39D-TTR was inhibited by diclofenac, which binds to the thyroxine channel in the tetramer, suggesting the existence of other pockets in A39D-TTR able to accommodate this molecule.
PubMed: 38925327
DOI: 10.1016/j.jbc.2024.107495 -
European Journal of Pharmacology Jun 2024Preeclampsia (PE) is often associated with multiple organ damage that remains noticeable postnatally. Here, we tested the hypotheses that antenatal therapy with...
Preeclampsia (PE) is often associated with multiple organ damage that remains noticeable postnatally. Here, we tested the hypotheses that antenatal therapy with nonsteroidal antiinflammatory drugs (NSAIDs) refashions liver damage induced by PE in weaning rats and that the high mobility group box 1 (HMGB1) signaling modulates this interaction. PE was induced by pharmacologic nitric oxide deprivation during the last week of gestation (N-nitro-L-arginine methyl ester, L-NAME, 50 mg/kg/day, oral gavage). Compared with control rats, weaning PE rats revealed substantial rises in serum transaminases together with histopathological signs of hepatic cytoplasmic changes, portal inflammation, and central vein dilation. While gestational NSAIDs reversed the elevated transaminases, they had no effects (celecoxib, naproxen) or even worsened (diclofenac) the structural damage. Molecularly, celecoxib was the most effective NSAID in (i) reversing PE-evoked upregulation of hepatic HMGB1 gene expression and concomitant increments and decrements in mitogen-activated protein kinases MAPK and MAPK expression, respectively, and (ii) elevating and suppressing serum interleukin-10 and tumor necrosis factor-α, respectively. Alternatively, rises in serum interleukin-1β and shifts in macrophage polarization towards an inflammatory phenotype caused by PE were comparably diminished by all NSAIDs. The data disclose an advantageous therapeutic potential for gestational celecoxib over diclofenac or naproxen in controlling hepatic dysfunction and HMGB1-interrelated inflammatory and oxidative sequels of PE.
PubMed: 38925287
DOI: 10.1016/j.ejphar.2024.176769 -
Pharmacy (Basel, Switzerland) Jun 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only...
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage pain, fever, and inflammation. Although most are usually classified as prescription-only medicines, in many countries they are frequently purchased for self-medication purposes. This study explores NSAID-usage patterns in Kosovo, aiming for a safer and more effective medicinal use. The study employed a dual approach to collect data. First, NSAID sales were analyzed in a convenience sample of ten community pharmacies across diverse regions in Kosovo in 2023. Second, data on NSAID-usage patterns and patient awareness were systematically gathered from 410 patients during routine pharmacist-patient interactions. The four most commonly purchased NSAIDs according to sales analysis were diclofenac (33.1%), ketoprofen (27.6%), ibuprofen (17.0%) and nimesulide (12.7%). A significant 74.8% of NSAIDs were bought without prescriptions, particularly among younger adults (20-39 years), who accounted for 82.8% of such purchases. The predominant reason for NSAID use was headache (43.8%). Although many of the patients suffered from occasional (33.7%) or frequent (12.6%) stomachaches and took acid-lowering medicines, the majority (85.9%) could not recall any NSAID adverse reactions. This study exposes widespread self-medication and a significant lack of awareness regarding potential risks of NSAIDs, particularly among young adults. To address these issues, it is critical to improve dispensing practices through increased pharmacist awareness and stricter law enforcement.
PubMed: 38921969
DOI: 10.3390/pharmacy12030093 -
ACS Applied Materials & Interfaces Jun 2024A peroxymonosulfate oxidation system was developed via modification of β-cyclodextrin (β-CD) on the surface of Fe-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The...
A peroxymonosulfate oxidation system was developed via modification of β-cyclodextrin (β-CD) on the surface of Fe-doped ZIF-67 (CD/Fe@ZIF-67) as an activator. The 99.7% carbamazepine, 91.3% bisphenol A (BPA), and 95.4% diclofenac (DCF) degradation efficiency were achieved within 10 min, 60, and 1 min, respectively. The hydrophobicity of these three pollutants is positively correlated with their adsorption kinetic constants by CD/Fe@ZIF-67 due to the introduction of β-CD. Scavenger experiments and electron spin resonance spectra confirmed that carbamazepine was preferentially oxidized by SO [λ(SO)(70.5%) > λ(OH)(28.2%) > λ(O)(1.3%)], where SO and O played dominant roles in the degradation of BPA [λ(SO)(71.7%) > λ(O)(22.8%) > λ(OH)(5.5%)], and O was responsible for DCF removal [λ(O) = 93.2%]. Additionally, the particulate catalyst was immobilized in the shell side of a ceramic membrane in a membrane reactor for catalyst recovery. This reactor achieved nearly 100% removal efficiency under optimal conditions: 0.036 wt % catalyst loading, 0.5 mM peroxymonosulfate concentration, 1 L inflow, 10 mg/L initial carbamazepine concentration, and 0.012 L/min hydraulic retention time. In summary, this study elucidates the active role of β-CD in a polymetallic/peroxymonosulfate system and provides valuable insights into the development of effective oxidation methods for pharmaceutical and personal care products in wastewater.
PubMed: 38918892
DOI: 10.1021/acsami.4c05315 -
ACS Applied Materials & Interfaces Jun 2024
PubMed: 38910290
DOI: 10.1021/acsami.4c09703