Diclofenac diethylammonium 1.16% gel

Abstract Effective co‐delivery of multiple drugs via microneedle (MN) platforms is challenging due to limited loading capacity and the need for sustained release. This study presents a bimodal coated‐dissolving microneedle (DMN) patch for extended delivery of diclofenac (DCF) and dexamethasone (DSP) nanoparticles to treat osteoarthritis. The DMN tips are loaded with DCF nanoparticles (3.84 mg/patch) and coated with DSP‐PLGA nanosuspensions (0.44 mg/patch), achieving dual‐drug release from a single patch. Ex vivo studies in neonatal porcine skin show > 90% penetration into the stratum corneum (≈276 µm depth), with transdermal delivery of 1.54 mg DCF and 118 µg DSP at 24 h. In vivo pharmacokinetic studies in rats demonstrate sustained DCF plasma levels for 72 h, with an extended half‐life (13.0 h) and 80.3% relative bioavailability compared to oral dosing. DSP exhibits a biphasic release, peaking at 24–30 h (227.7 ng mL −1 , 63.9% bioavailability). High drug levels persist in skin and paw tissues for 72 h, suggesting prolonged local efficacy. These bimodal DMNs provide a high‐loading, sustained‐release platform for minimally invasive, patient‐friendly dual‐drug therapy, optimizing osteoarthritis treatment and improving compliance.

Abstract licence: CC BY

Skin penetration of an active pharmaceutical ingredient is key to developing topical drugs. This penetration can be adjusted for greater efficacy and/or safety through the selection of dosage form. Two emerging dosage forms, cream–gel and gel-in-oil emulsion, were tested for their ability to deliver diclofenac into the skin, with the target of maximising skin retention while limiting systemic exposure. Prototypes with varying amounts of solvents and emollients were formulated and evaluated by in vitro penetration testing on human skin. Cream–gel formulas showed better skin penetration than the emulgel benchmark drug even without added solvent, while gel-in-oil emulsions resulted in reduced diffusion of the active into the receptor fluid. Adding propylene glycol and diethylene glycol monoethyl ether as penetration enhancers resulted in different diclofenac penetration profiles depending on the dosage form and whether they were added to the disperse or continuous phase. Rheological characterisation of the prototypes revealed similar profiles of cream–gel and emulgel benchmark, whereas gel-in-oil emulsion demonstrated flow characteristics suitable for massaging product into the skin. This study underlined the potential of cream–gel and gel-in-oil emulsions for adjusting active penetration into the skin, broadening the range of choices available to topical formulation scientists.

Abstract licence: CC BY

Diclofenac diethylammonium belongs to the class of non-steroidal anti-inflammatory drugs, and it is widely used to relieve pain and reduce systemic inflammation. This drug exists in polymorphic forms, which can directly affect the ability to process the drug, as well as drug product dissolution, stability, and bioavailability. Considering the worldwide regulatory guidance for polymorphs in drug substances, a detailed structural analysis of two polymorphs exhibiting the anhydrous and monohydrated structures of diclofenac diethylammonium is presented here, using the supramolecular arrangement and its relationship with structural-physicochemical properties. The polymorph’s structures show conformational differences in the carboxylic group caused by coordinated water molecules presented in the monohydrated polymorphic structure. Both polymorphs have the supramolecular arrangement stabilized by NH···O and CH···Cl intermolecular interactions, but the monohydrated molecule presents a strong OH···O intermolecular interaction due to the presence of a water molecule. Hirshfeld surface analysis showed CH···π and π···π contacts in the anhydrous and monohydrated polymorphs, respectively. Theoretical results, including solvent effect with explicit and implicit approaches for water, indicated the kinetic stability of the diclofenac diethylammonium drug and showed susceptible electrophilic attacks occurring in the region close to the carbonyl oxygen atom.

Abstract licence: CC BY-NC-ND

Plant-based food supplements (FS) of doubtful traceability have now emerged as a new threat to human health. Food supplements adulterated with pharmaceutical ingredients are considered "medicines in disguise" by regulatory authorities, which is a sub-category of falsified medicines. In the context of illegal manufacture and trade, as well as in the absence of an official phyto- and/or pharmacovigilance system, emergency departments and poison control centers constitute a early warning system for detecting ingested suspect FS. In the present investigation, we set up efficient workflows for the systematic characterization of adulterated plant-based FS in the context of an original local early warning alert system (i.e., FalsiMedTrack) involving an emergency department, a poison center, and academic analytical chemistry laboratories. Fit-for-purpose cross-analytical methods were employed, including sophisticated methods such as liquid chromatography coupled to high-resolution mass spectrometry, nuclear magnetic resonance, X-ray powder diffraction, as well as the most accessible and affordable HPLC method with UV/DAD detection. The strategy was applied successfully to typical cases of suspect plant-based health products, i.e., sample incriminated in patients experiencing side effects and herbal products currently commercialized for their "amazing health benefits". The samples contained active pharmaceutical ingredients, including diclofenac, piroxicam, dexamethasone 21-acetate, and sibutramine. We provided evidence of "medicines in disguise" presented as food supplements, which raises concerns about their quality and safety.

Abstract licence: CC BY

This study investigated whether liposomes could enhance the permeation and penetration of diclofenac diethylammonium. For this, a 1.16% diclofenac diethylammonium liposome gel formulation was developed (Grupo Leti, S.A.V.). In vitro and ex vivo tests were conducted to analyze the diffusion and penetration profiles of the formulation. The profiles obtained were compared with a commercially available product, DiAnalper gel (Pharmetique Labs). The in vitro test was assessed in a Franz diffusion cell system using a dialysis membrane. The cumulative amount of drug permeated after 24 h demonstrated a significantly (p 2, whereas the commercial formulation yielded values of 371.00 ± 3.54 μg/cm2. These findings were further supported by consistent results in the percentage of drug release, flux, and permeability coefficient, all indicating a notable improvement in diffusion associated with the liposomal gel formulation. The tape stripping assay performed on pig ear skin demonstrates a statistically significant difference (p < 0.05) between the penetration transport of the diclofenac from liposome gel formulation (1413.95 ± 250.51 μg) and the conventional product (202.36 ± 18.07 μg) the liposomal formulation was able to cross de stratum corneum and deliver a high amount of drug to the skin. These findings demonstrated that incorporating diclofenac into a liposomal system significantly improved the drug delivery, which could confer an advantage for clinical uses.

Abstract licence: CC BY

The objective of this research was to develop water-based extracts of Thai spices, prepared using traditional decoction techniques, to assess their potential medicinal properties. These extracts provide a foundation for developing a Thai spice-based oral spray. To achieve this, the study investigated the in vitro anti-inflammatory activity which was assessed using the albumin denaturation inhibition method with egg albumin, and compared that to the standard drug Diclofenac diethylammonium. The antibacterial properties against the oral pathogenic bacterium Streptococcus mutans (S. mutans) were tested using the disc diffusion method and compared with the standard antibiotic Erythromycin, and total tannin content using the Folin-Ciocalteu colorimetric technique. The extraction process was enhanced through the application of the reflux method to optimize the development of the extracts. Three types of Thai spices; Chinese cinnamon (Cinnamomum cassia L.), clove (Syzygium aromaticum), and star anise (Illicium verum), were extracted using water as a solvent, with a ratio of 1:10 (w/v). The extraction process was conducted for two different durations, resulting in six extract samples as 1-hour extractions; Chinese cinnamon extract (E1A), clove extract (E1B), and star anise extract (E1C), and 3-hour extractions; Chinese cinnamon extract (E3A), clove extract (E3B), and star anise extract (E3C). These six extracts were tested for their in vitro anti-inflammatory activity, antibacterial activity against S. mutans, and total tannin content. The results showed that E1B exhibited the strongest in vitro anti-inflammatory activity, with an IC50 value of 1.17±0.05 mg/ml, which was significantly higher than that of the other extracts (p&lt;0.05). Additionally, extracts obtained from 1-hour extraction demonstrated higher anti-inflammatory effects than 3-hour extraction. Furthermore, E1B contained the highest total tannin content (87.89±2.51 mg TAE/g extract). However, when tested for antibacterial activity against S. mutans, none of the six extracts showed any inhibitory effects compared to the standard antibiotic Erythromycin (23.23±0.17 mm). This finding is crucial for future studies exploring these Thai spices for many medicinal uses, particularly their potential as natural anti-inflammatory agents in various products."

Abstract licence: CC BY-NC