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The developed method for simultaneous detection of levodopa and carbidopa was able to separate the peaks of the drug and sodium bisulfite in the in-vitro release samples and stability samples. Levodopa (LD), a pro-drug of dopamine, is used as the gold standard treatment for Parkinson's disease. It is usually prescribed with carbidopa (CD) to prevent the conversion of levodopa to dopamine peripherally, thus reducing undesirable side effects. Both drugs are unstable at pH 7.4 beyond 24 h due to their oxidation, therefore 0.2% sodium bisulfite is added to the formulation as an antioxidant. The separation was performed by gradient elution using the Luna-C18 column (250 × 4.6 mm, 5 µm) at a flow rate of 1 ml/min. The mobile phase was composed of mobile phase A 30 mM potassium phosphate and acetonitrile (95:5, v/v) with 35 mM tetrabutylammonium hydrogen sulphate and mobile phase B containing 30 mM potassium phosphate and acetonitrile (50:50 v/v). Drug peaks were detected at 280 nm with retention times of 3.05 ± 0.001 min for LD and 3.64 ± 0.001 min for CD. The validation of the method according to US FDA guidelines and results were found to be within acceptable limits. The method was linear from 10–100 µg/ml (r2 = 0.999) and 10–100 µg/ml (r2 = 0.999) for LD and CD, respectively. The developed method was applied to studying the drug release from in-situ gel. The environmental impact of the developed method was evaluated using various greenness assessment tools. [ABSTRACT FROM AUTHOR]

Background: Treatment of cutaneous wound infections is becoming a major clinical challenge due to the growing problem of antimicrobial resistance associated with existing wound treatments. Two prevalent pathogens in wound infections, Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), continue to present a serious challenge, underscoring the critical need for new therapeutic alternatives. Methods: Novel alginate acid-buffered gels (ABF-1, ABF-2, and ABF-3) were developed using a combination of organic acids in various concentrations and buffered at a pH of 4.5. The acid-buffering capacity of the gels was evaluated against sodium hydroxide solution and simulated wound fluid (SWF) at different wound pHs, mimicking infected and non-infected wound environments. The in vitro antibacterial activity was assessed against resistant bacterial strains (Gram-positive and Gram-negative) using a microdilution method and wound biofilm assay. The rheological properties and cell viability of the gels were evaluated and the gel showing positive cell viability was further investigated for healing ability using an in vitro wound scratch assay. Results: The gels showed promising in vitro antibacterial activity against Staphylococcus epidermidis, S. aureus, and P. aeruginosa. Gels with higher acid concentrations (ABF-1 and ABF-2) were highly effective in reducing the bacterial load in chronic biofilms of S. aureus and P. aeruginosa, while the gel with a lower acid concentration (ABF-3) showed positive effects on the viability of skin cells (over 80% cells viable) and for promoting wound closure. All three gels demonstrated excellent acid-buffering capabilities. Conclusions: The acid-buffered gels demonstrate promising in vitro antibacterial effects, indicating their potential for enhancing wound healing. [ABSTRACT FROM AUTHOR]

5-fluorouracil (5-FU), commercially available as a topical product, is approved for non-melanoma skin cancer (NMSC) treatment with several clinical limitations. This work aimed to develop 5-FU-loaded topical patches as a potential alternative to overcome such drawbacks. The patches offer accurate dosing, controlled drug release and improved patient compliance. Our study highlights the development of Eudragit® E (EuE)-based drug-in-adhesive (DIA) patches containing a clinically significant high level of 5-FU (approximately 450 µg/cm2) formulated with various chemical permeation enhancers. The patches containing Transcutol® (Patch-TRAN) or oleic acid (Patch-OA) demonstrated significantly higher skin penetration ex vivo than their control counterpart, reaching 5-FU concentrations of 76.39 ± 27.7 µg/cm2 and 82.56 ± 8.2 µg/cm2, respectively. Furthermore, the findings from in vitro permeation studies also validated the superior skin permeation of 5-FU achieved by Patch-OA and Patch-TRAN over 72 h. Moreover, the EuE-based DIA patch platform demonstrated suitable adhesive and mechanical properties with an excellent safety profile evaluated through an inaugural in vivo human study involving 11 healthy volunteers. In conclusion, the DIA patches could be a novel alternative option for NMSC as the patches effectively deliver 5-FU into the dermis layer and receptor compartment ex vivo for an extended period with excellent mechanical and safety profiles. [ABSTRACT FROM AUTHOR]