Transdermal drug delivery systems (TDDSs) have become innovative, fascinating drug delivery methods intended for skin application to achieve systemic effects. TDDSs overcome the drawbacks associated with oral and parenteral routes of drug administration. The current investigation aimed to design, evaluate and optimize methotrexate (MTX)-loaded transdermal-type patches having ethyl cellulose (EC) and hydroxypropyl methyl cellulose (HPMC) at different concentrations for the local management of psoriasis. In vitro release and ex vivo permeation studies were carried out for the formulated patches. Various formulations (F1–F9) were developed using different concentrations of HPMC and EC. The F1 formulation having a 1:1 polymer concentration ratio served as the control formulation. ATR–FTIR analysis was performed to study drug–polymer interactions, and it was found that the drug and polymers were compatible with each other. The formulated patches were further investigated for their physicochemical parameters, in vitro release and ex vivo diffusion characteristics. Different parameters, such as surface pH, physical appearance, thickness, weight uniformity, percent moisture absorption, percent moisture loss, folding endurance, skin irritation, stability and drug content uniformity, were studied. From the hydrophilic mixture, it was observed that viscosity has a direct influence on drug release. Among all formulated patches, the F5 formulation exhibited 82.71% drug release in a sustained-release fashion and followed an anomalous non-Fickian diffusion. The permeation data of the F5 formulation exhibited about a 36.55% cumulative amount of percent drug permeated. The skin showed high retention for the F5 formulation (15.1%). The stability study indicated that all prepared formulations had very good stability for a period of 180 days. Therefore, it was concluded from the present study that methotrexate-loaded transdermal patches with EC and HPMC as polymers at different concentrations suit TDDSs ideally and improve patient compliance for the local management of psoriasis.

This study attempted to develop and evaluate controlled-release matrix-type transdermal patches with different ratios of hydrophilic polymers (sodium carboxymethylcellulose and hydroxypropyl methylcellulose) for the local delivery of methotrexate. Transdermal patches were formulated by employing a solvent casting technique using blends of sodium carboxymethylcellulose (CMC-Na) and hydroxypropylmethylcellulose (HPMC) polymers as rate-controlling agents. The F1 formulated patch served as the control formulation with a 1:1 polymer concentration. The F9 formulation served as our optimized formulation due to suitable physicochemical properties yielded through the combination of CMC-Na and HPMC (5:1). Drug excipient compatibilities (ATR-FTIR) were performed as a preformulation study. The ATR-FTIR study depicted great compatibility between the drug and the polymers. Physicochemical parameters, kinetic modeling, in vitro drug release, ex vivo drug permeation, skin drug retention, and in vivo studies were also carried out for the formulated patches. The formulated patches exhibited a clear, smooth, elastic nature with good weight uniformity, % moisture uptake, drug content, and thickness. Physicochemical characterization revealed folding endurance ranging from 62 ± 2.21 to 78 ± 1.54, tensile strength from 9.42 ± 0.52 to 12.32 ± 0.72, % swelling index from 37.16 ± 0.17 to 76.24 ± 1.37, and % drug content from 93.57 ± 5.34 to 98.19 ± 1.56. An increase in the concentration of the CMC-Na polymer (F9) resulted in increased drug release from the formulated transdermal patches. Similarly, drug permeation and retention were found to be higher in the F9 formulation compared to the other formulations (F1–F8). A drug retention analysis revealed that the F9 formulation exhibited 13.43% drug retention in the deep layers of the skin compared to other formulations (F1–F8). The stability study indicated that, during the study period of 60 days, no significant changes in the drug content and physical characteristics were found. ATR-FTIR analysis of rabbit skin samples treated with the formulated transdermal patches revealed that hydrophilic polymers mainly affect the skin proteins (ceramide and keratins). A pharmacokinetic profile revealed Cmax was 1.77.38 ng/mL, Tmax was 12 h, and t1/2 was 17.3 ± 2.21. In vivo studies showed that the skin drug retention of F9 was higher compared to the drug solution. These findings reinforce that methotrexate-based patches can possibly be used for the management of psoriasis. This study can reasonably conclude that methotrexate transdermal matrix-type patches with CMC-Na and HPMC polymers at different concentrations effectively sustain drug release with prime permeation profiles and better bioavailability. Therefore, these formulated patches can be employed for the potential management of topical diseases, such as psoriasis.

Metronidazole has the potential to produce local stomach specific action in order to treat Helicobacter pylori induced peptic ulcer disease. The current project executes the development of osmotically controlled bioadhesive metronidazole loaded effervescent floating tablets with optimized floating and swelling behavior. Direct compression technique was used to prepare the tablets. The designed formulations exhibited physico-chemical properties within acceptable optimum limits as per pharmacopeial requirements. The results of tablet floating studies revealed that all formulations, except F1 and F5, had good buoyancy characteristics (TFT > 12 h except F2 and F8 with TFT of 6 h). Formulation F2 containing guar gum in higher concentration with carbopol and formulation F8 containing guar gum in 50% decreased concentration in combination with HPMC and carbopol had enhanced FLT appreciably, with least TFT as compared to formulations F3, F4, and F6 (ANOVA; p ≤ 0.05). Formulation batches of F3, F4, and F6 exhibited appreciable FLT as well as TFT and were optimized formulations. Out of the above mentioned optimized batches, F4 and F6 formulations showed low FLT (4 and 5 s respectively). The results of the swelling study indicated a proportionate increase in the swelling index with increase in time. A significantly higher swelling ratio was found with formulation F6 and F4 compared with that of F7 and F8 (ANOVA; p ≤ 0.05). Additionally, the impact of pH change, agitational intensity, as well as increasing concentration of NaCl was investigated on drug release. It was observed that agitational intensity had no effect on drug release rate while increasing concentration of NaCl produced an increased drug release from the dosage form as compared to the drug release exhibited by the formulations in the absence of NaCl. Overall, this project could have valuable contribution in the fabrication of metronidazole loaded effervescent floating tablets. Gastro-retentive systems are expected to enhance local stomach specific action of anti H. pylori agents based on their buoyancy and swelling behavior.

Psoriasis, a chronic inflammatory illness, is on the rise and is linked to several other life-threatening diseases. The primary goal of this study was to create a nanoemulsion gel loaded with methotrexate and olive oil (MTX NEG). The formulation was evaluated for physicochemical characterization, entrapment efficiency, drug release kinetics, skin permeation studies and stability tests. In addition, the efficacy of MTX NEG against psoriasis was tested using imiquimod-induced psoriasis in a rat model. The final optimized MTX NEG was developed with a particle size of 202.6 ± 11.59 nm and a PDI of 0.233 ± 0.01, with a 76.57 ± 2.48% average entrapment efficiency. After 20 h, the release kinetics predicted a 72.47% drug release at pH 5.5. FTIR findings demonstrated that the optimized MTX NEG formulation effectively fluidized both the epidermis and dermis of the skin, potentially increasing drug permeability and retention. The application of Tween 80 and PEG 400, on the other hand, significantly enhanced these effects, as these are well known penetration enhancers. After 24 h, an average of 70.78 ± 5.8 μg/cm2 of methotrexate was permeated from the nanoemulsion gel with a flux value of 2.078 ± 0.42 μg/cm2/h, according to permeation measurements. Finally, in vivo experiments on rabbit skin revealed that the increased skin penetration of methotrexate-loaded nanoemulsion gel was not due to structural alterations in intercellular lipid layers in the stratum corneum. In vivo antipsoriatic studies on rats revealed that MTX NEG produced a PASI decrease that was extremely similar and even better than the 91% reduction seen in the MTX tablet group. According to the pharmacokinetic profile, Cmax was 8.5 μg/mL, Tmax was 12 h, and t1/2 was 15.5 ± 2.37 h. These findings reinforce that MTX-NEG based on olive oil could be a possible treatment for psoriasis and could decrease the remission of psoriasis-like symptoms.

(1) Background: Bacitracin is a broad spectrum antibiotic that is used against various microorganisms. Chitosan is a natural polymer that has been widely investigated as an antimicrobial agent for preventing and treating infections owing to its intrinsic antimicrobial properties, as well as its ability to effectively deliver extrinsic antimicrobial compounds to infected areas. Topical drug delivery offers important benefits for improving the therapeutic effect and reducing systemic side effects of administered compounds/drugs. The topical use of chitosan-decorated bacitracin-loaded cream improves the permeation of the drug across the skin and enhances the drug bioavailability by prolonging the residence time of the drug when applied topically, as well as producing synergistic effects and reducing the side effects of the drug. Topical chitosan-decorated cream can be a promising approach to administer the drug more efficiently and enhance the efficacy of treatment in wound healing and antibacterial activity. (2) Methods: This study was conducted to prepare, assess and investigate the synergistic antibacterial activity of a chitosan-coated bacitracin cream. The results were compared to the antibacterial activity of simple bacitracin-loaded cream. The prepared cream was evaluated for various in vitro characteristics such as rheology, pH, viscosity, drug content and antibacterial activity studies. (3) Result: The formulations were found to be stable regarding color, liquefaction and phase separation at all accelerated conditions. It was observed that with time, substantial variations in the pH of the preparations were found. The introduction of chitosan results in controlled release of the drug from the formulations. The antibacterial activity of the formulated creams was assessed with the disc diffusion method against Staphylococcus aureus(ATCC),Escherichiacoli (STCC),Pseudomonas aeruginosa(ATCC) and Bacillus cereus(ATCC). The strains, E. coli, S. aureus, P. aeruginosa and B. cereus were susceptible to 50 µg chitosan-decorated bacitracin cream, showing inhibition zones of 10 ± 0.6, 34 ± 1.5, 31 ± 0.76 and 21 ± 2.02 mm, respectively. The zones of inhibition for simple bacitracin-loaded cream were significantly smaller than chitosan-decorated cream, at 2 ± 0.2, 28 ± 0.92, 15 ± 0.5 and 11 ± 1.25 mm (ANOVA; p < 0.05), respectively. (4) Conclusion: It was observed that the zones of inhibition of simple bacitracin-loaded cream were significantly smaller than those of chitosan-decorated bacitracin-loaded cream. Chitosan synergistically improves the antimicrobial activity of bacitracin. Hence, the developed formulation was effective and should be considered as a suitable candidate for topical management of skin infections and wound healing.