Collaterally Sensitive ß-Lactam Drugs as an Effective Therapy against the Pre-Existing Methicillin Resistant Staphylococcus aureus (MRSA) Biofilms.

Methicillin-resistant Staphylococcus aureus (MRSA) is among the leading causes of nosocomial infections and forms biofilms, which are difficult to eradicate because of their increasing resistance to antimicrobial agents. This is especially true for pre-existing biofilms. The current study focused on evaluating the efficacy of three ß-lactam drugs, meropenem, piperacillin, and tazobactam, alone and in combination against the MRSA biofilms. When used individually, none of the drugs exhibited significant antibacterial activity against MRSA in a planktonic state. At the same time, the combination of meropenem, piperacillin, and tazobactam showed a 41.7 and 41.3% reduction in planktonic bacterial cell growth, respectively. These drugs were further assessed for biofilm inhibition and removal. The combination of meropenem, piperacillin, and tazobactam caused 44.3% biofilm inhibition, while the rest of the combinations did not show any significant effects. Results also revealed that piperacillin and tazobactam exhibited the best synergy against the pre-formed biofilm of MRSA, with 46% removal. However, adding meropenem to the piperacillin and tazobactam combination showed a slightly reduced activity towards the pre-formed biofilm of MRSA and removed 38.7% of it. Although the mechanism of synergism is not fully understood, our findings suggest that these three ß-lactam drugs can be used in combination as very effective therapeutic agents for the treatment of pre-existing MRSA biofilms. The in vivo experiments on the antibiofilm activity of these drugs will pave the way for applying such synergistic combinations to clinics.

Development and Evaluation of Essential Oil-Based Nanoemulgel Formulation for the Treatment of Oral Bacterial Infections.

Prevalence of oral infections in diabetic patients is a health challenge due to persistent hyperglycemia. However, despite great concerns, limited treatment options are available. We therefore aimed to develop nanoemulsion gel (NEG) for oral bacterial infections based on essential oils. Clove and cinnamon essential oils based nanoemulgel were prepared and characterized. Various physicochemical parameters of optimized formulation including viscosity (65311 mPa·S), spreadability (36 g·cm/s), and mucoadhesive strength 42.87 N/cm2) were within prescribed limits. The drug contents of the NEG were 94.38 ± 1.12% (cinnamaldehyde) and 92.96 ± 2.08% (clove oil). A significant concentration of clove (73.9%) and cinnamon essential oil (71.2 %) was released from a polymer matrix of the NEG till 24 h. The ex vivo goat buccal mucosa permeation profile revealed a significant (52.7-54.2%) permeation of major constituents which occurred after 24 h. When subjected to antimicrobial testing, significant inhibition was observed for several clinical strains, namely Staphylococcus aureus (19 mm), Staphylococcus epidermidis (19 mm), and Pseudomonas aeruginosa (4 mm), as well as against Bacillus chungangensis (2 mm), whereas no inhibition was detected for Bacillus paramycoides and Paenibacillus dendritiformis when NEG was utilized. Likewise promising antifungal (Candida albicans) and antiquorum sensing activities were observed. It was therefore concluded that cinnamon and clove oil-based NEG formulation presented significant antibacterial-, antifungal, and antiquorum sensing activities.

Primary percutaneous coronary intervention in CAD patients: A comparison of major adverse cardiovascular events of second- and third-generation drug-eluting stents.

Background: Biodegradable polymer (BP) drug-eluting stents (DES) have been introduced as a novel solution to the problems of durable polymer (DP) stents. In Pakistan, very few studies are available for the treatment intervention in post-primary percutaneous coronary intervention (PPCI) patients. Our study will compare the major adverse cardiovascular events (MACEs) and their predictors in patients with coronary artery disease (CAD) undergoing PPCI with second- or third-generation DES. Methodology: An observational, retrospective, cohort study was carried out on CAD patients undergoing PPCI with either second- (DP-XIENCE Prime/XIENCE Xpedition) or third-generation (BP-BioMatrix NeoFlex/BioMatrix Alpha) DES. MACEs were assessed after 1 year of PPCI procedure in 341 patients and screened as per inclusion/exclusion criteria (167 in the second-generation group and 174 in the third-generation group). Results: The number of male patients (86.2%) was more than female patients in our study population. MACEs were reported in 4.19% patients after 1 year duration, and the percentage of MACEs was more in the second-generation DES group (4.77%) than in the third-generation group (3.44%); however, statistical analysis has not found any significant difference (p = 0.534). The rate of myocardial infarction (1.19% vs. 0.57%) and stent thrombosis (1.8% vs. 1.15%) was more in the second-generation DES group. However, restenosis (1.19% vs. 1.15%) and cardiac death (0.59% vs. 0.57%) were almost same in both groups. A significant association was found between MACEs and diabetes mellitus (p = 0.025), hypertension (p = 0.035), smoking (p = 0.008), and a family history of CAD (p = 0.018). Conclusion: BP-BioMatrix and DP-XIENCE DES have comparable clinical outcomes. Findings of the current study will assist the policy makers and healthcare providers in the rationalization of scarce resources and evidence-based patient care. However, longer follow-up studies are required for convincing results.

Molecular Modeling Study of Novel Lancifolamide Bioactive Molecule as an Inhibitor of Acetylcholinesterase (AChE), Herpes Simplex Virus (HSV-1), and Anti-proliferative Proteins.

Combretaceae, an immense family involving species (500) or genera (20), originates in tropical and subtropical regions. This family has evinced medicinal values such as anti-leishmanial, cytotoxic, antibacterial, antidiabetic, antiprotozoal, and antifungal properties. Conocarpus lancifolius (C. lancifolius) methanol extract (CLM) was prepared, then compound isolation performed by open column chromatography, and compound structure was determined by spectroscopic techniques (13C NMR, IR spectroscopy, 1H-NMR, mass spectrometry UV-visible, and 2D correlation techniques). Molecular docking studies of ligand were performed on transcriptional regulators 4EY7 and 2GV9 to observe possible interactions. Phytochemical screening revealed the presence of secondary metabolites including steroids, cardiac glycosides, saponins, anthraquinones, and flavonoids. The isolated compound was distinguished as lancifolamide (LFD). It showed cytotoxic activity against human breast cancer, murine lymphocytic leukemia, and normal cells, human embryonic kidney cells, and rat glioma cells with IC50 values of 0.72 µg/mL, 2.01 µg/mL, 1.55 µg/mL, and 2.40 µg/mL, respectively. Although no cytotoxic activity was noticed against human colon cancer and human lung cancer, LFD showed 24.04% inhibition against BChE and 60.30% inhibition against AChE and is therefore beneficial for Alzheimer's disease (AD). AChE and LFD interact mechanistically in a way that is optimum for neurodegenerative disorders, according to molecular docking studies. Methanol and dichloromethane extract of C. lancifolius and LFD shows antibacterial and antifungal activity against antibiotic resistance Bacillus subtilis, Streptococcus mutans, Brevibacillus laterosporus, Salmonella Typhi, Candida albicans, and Cryptococcus neoformans, respectively. LFD shows antiviral activity against HSV-1 with 26% inhibition IP. The outcomes of this study support the use of LFD for cognitive disorders and highlight its underlying mechanism, targeting AChE, DNA-POL, NF-KB, and TNF-α, etc., for the first time.

Formulation, In Vitro Characterization and Antibacterial Activity of Chitosan-Decorated Cream Containing Bacitracin for Topical Delivery.

(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.

Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability.

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures.

Formulation of Polymers-Based Methotrexate Patches and Investigation of the Effect of Various Penetration Enhancers: In Vitro, Ex Vivo and In Vivo Characterization.

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug-excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed Cmax ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, Tmax was 8 h to 10 h, and t1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis.

Impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients: a prospective cohort study.

OBJECTIVES: Poor control of asthma in the majority of patients could be partly due to their lack of knowledge concerning disease management, its triggering agents and when to seek advice from the healthcare provider. This study aims to assess the impact of pharmacist-led educational intervention on knowledge of self-management among asthmatic patients. DESIGN: A pre-post cohort study. SETTING: Outpatient department of a tertiary care hospital affiliated with Quaid-i-Azam University, Pakistan. PARTICIPANTS: Approximately 265 adult asthmatic patients selected through a spirometry process, aged ≥18 years, were approached. 240 patients gave consent to participate in the study and were divided into control and treatment groups. INTERVENTIONS: The educational intervention consisted of individual patient counselling using educational material with time varied according to each patient's comprehension and previous knowledge. PRIMARY AND SECONDARY OUTCOME MEASURES: Assessment consisted of a 14-item Asthma Self-Management Knowledge Questionnaire (ASMQ) quantifying a patient's self-management knowledge through an ASMQ score and its change following an educational intervention. RESULTS: Disease self-management knowledge was low with an average raw ASMQ score of 4.1 (max 14); which equates to a transformed score of 29.34 (max 100) and the proportion of patients who correctly answered more than 50% of questions were 16.7% preintervention. More than half of the participants (55%) did not know that asthma cannot be cured. The administration of educational intervention protocols resulted in significantly improved level of knowledge of asthma self-management (<0.001) in the treatment group (mean ASMQ score improved from 4.20 to 9.77). CONCLUSION: On baseline visit, patients possessed a poor knowledge about asthma self-management. Educational intervention protocols had a positive impact on improving patients' knowledge about disease self-management. This would suggest that education and self-management skills should be seen as an integral component of asthma management and should be incorporated in structured patient care to achieve optimal asthma control.

Lornoxicam-Loaded Chitosan-Decorated Nanoemulsion: Preparation and In Vitro Evaluation for Enhanced Transdermal Delivery.

Nanoemulsions are promising drug delivery systems for the administration of poorly soluble drugs like lornoxicam (LRX) by oral or parenteral routes. Such formulations work perfectly for transdermal delivery of lornoxicam-type drugs. It has also been established that formulating such a delivery system is highly dependent on the presence, type, and concentration of excipients taking part in the formulation. The inherent characteristics of nanoemulsion (NE), i.e., smaller globule size and excipient nature, facilitate the drug's passage through skin. The current study was aimed at the development of an NE-based formulation of LRX to improve the drug solubility in vitro as well as to enhance drug skin permeation to promote therapeutic outcome in appropriate time. Spontaneous self-emulsification technique was utilized to develop optimized LRX-encapsulated NE-based formulations. ATR-FTIR spectra of the pure drug and various formulations did not show any interaction between the drug and various formulation excipients showing compatibility. Globule size for stable formulations ranged between 63-168 nm. These formulations were characterized for viscosity, surface tension, pH, drug encapsulation efficiency, in vitro drug release, and drug skin permeation studies. Chitosan-decorated optimized NE formulation of LRX showed about 58.82% cumulative drug release, showing an anomalous non-Fickian diffusion mechanism of drug release. Drug encapsulation efficiency, in vitro drug release, and skin permeation studies exhibited promising results. An appreciable drug entrapment efficiency was exhibited by optimized NE formulations LRX-6, 71.91 ± 3.17% and C-LRX, 65.25 ± 4.89%. Permeability parameters like enhancement ratio (Er), permeability constant (Kp), and steady state flux (Jss) showed higher values and exhibited good results based on formulation type. The selected promising formulation type "LRX-6" showed significantly different results as compared to other formulations (LRX-4, 5, and 7). The skin permeation property of the LRX-6 formulation was compared to similar chitosan-based formulations and was found to have better skin permeation results than chitosan-based formulations. This study clearly exhibited that an LRX-containing NE-based formulation can be formulated to form a stable drug delivery system. Such formulations are promising in terms of physicochemical characteristics, improved solubility, and high skin permeation potential.

A Novel Distachionate from Breynia distachia Treats Inflammations by Modulating COX-2 and Inflammatory Cytokines in Rat Liver Tissue.

Breynia distachia is a plant of genus Breynia belonging to family Phyllanthaceae. This study was conducted to isolate and examine the anti-inflammatory attributes of the roots of Breynia distachia. Methanol extract from roots were prepared by simple maceration. For phytochemical studies, isolation, purification, structure elucidation, metal analysis, total phenolic content, and solubility test were done by chromatographic and spectroscopic techniques. Anti-inflammatory activity was evaluated by cotton pallet edema model and carrageenan paw edema model, and antioxidant potential was evaluated by DPPH, FRAP, and ABTS antioxidants assays. Metal analysis of BD.Me revealed the presence of Na > Mg > K > Mn > Fe = Zn in respective order. Four phytochemicals such as gallic acid, quercetin, sinapic acid, and p-coumaric acid are found in Breynia distachia. Quercetin is present in relatively larger quantity, and shows antioxidant activity by reducing the ferric iron to ferrous iron. Novel distachionate shows high antioxidant activity in ABTS assay by reducing reactive oxygen species. Quantitative or qualitative analysis performed by HPLC indicates the ascending peaks or presence of secondary products (metabolites) respectively. Histopathology analysis of liver, spleen, heart, and kidney was done, revealing mild inflammations in spleen and liver, and no cytotoxicity in heart and kidney. Oral administration of BD.Me and ditachionate significantly inhibits the carrageenan and cotton pellet-induced paw edema in 1st and 2nd h with (ns = p > 0.05) than control. After 3rd, 4th, 5th, and 6th h, BD.Me and ditachionate showed inhibition of paw edema in a highly significant (*** = p < 0.001) manner as compared to control. In cotton-pellet edema model, distachionate shows a %inhibition of 57.3% at a dose level of 5 mg/kg. Docking values obtained from distachionate-COX-2 complex suggest a potent inhibitor evaluated for this protein. The distachionate shows effective anti-inflammatory activity. Methanol extracts of roots showed significant lipoxygenase inhibitory activity by IC50 values of 155.7 ± 0.55 and 132.9 ± 0.33 µg/mL. Data from various in vitro and in vivo models suggest that novel distachionate isolated from Breynia distachia shows strong antioxidant and anti-inflammatory activities; it should be further studied for the exploration of its medicinal potential.

Formulation and Evaluation of Hydrophilic Polymer Based Methotrexate Patches: In Vitro and In Vivo Characterization.

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.

Optimization and validation of an analytical method for the estimation of methotrexate in rabbit plasma.

Methotrexate (MTX) is an anticancer drug used for the treatment of various cancers and autoimmune diseases. In this study, High Performance Liquid Chromatography (HPLC) method was developed and validated for the estimation of MTX in rabbit plasma with high estimation rate and recovery. Various validation parameters like, sensitivity, sample recovery, accuracy and precision analysis were studied. The pre-saturated reversed C18 end capped HPLC column was used to separate MTX present in rabbit plasma. A solvent mixture of 100mM phosphate buffer pH 7.4 and acetonitrile (92:8 percent v/v) was employed as the mobile phase. Analysis was carried out at ʎ max 303 nm and retention time of MTX was found 5.32 min. During the method development and validation ICHQ2 (R1) guidelines were strictly followed. Developed method was found excellent in terms of recovery of MTX from plasma samples (98.6%). It is obvious from the current study that the developed HPLC method can be utilized to analyze the level of MTX in patients. Furthermore, the cost of the developed method for the determination of MTX would be very low as compared to the previously reported methods.

Metronidazole Based Floating Bioadhesive Drug Delivery System for Potential Eradication of H. pylori: Preparation and In Vitro Characterization.

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.

Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-like Skin Inflammation in an Animal Model.

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.

Ethyl Cellulose and Hydroxypropyl Methyl Cellulose Blended Methotrexate-Loaded Transdermal Patches: In Vitro and Ex Vivo.

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.

Development, characterization and optimization of methotrexate-olive oil nano-emulsion for topical application.

The chronic inflammatory conditions like psoriasis has an increased prevalence and is linked with various associated life threatening disease conditions. The main objective of this project was to developed a methotrexate-olive loaded nano emulsion. The formulation was assessed for various parameters including Thermodynamic Stability, physico-chemically characterization, drug release kinetics and entrapment efficiency and in vitro/ in vivo skin permeation analysis. Final optimized formulation had a particle size 18.27±5.78 nm with a PDI of 0.25±0.01, whereas the average entrapment efficiency of formulation was 74.68±2.1%. The release kinetics suggested 97.72% drug release at pH 5 after 20 hrs. The FTIR data confirmed that the chemical structure of drug is retained with efficient loading into the formulation. Permeation data showed that an average of 79.23±3.6µg/cm2 of methotrexate was permeated from the nano emulsion with an average flux of 2.326±0.45µg/cm2/h after 24 hrs. Finally in vivo studies on rabbit skin confirmed that the structural changes of intercellular lipid layers in the stratum corneum are not responsible for enhanced skin permeation of methotrexate loaded nano emulsion. It was concluded that olive oil based MTX-NE is suitable for topical application and can be used for management of psoriasis.

Antibacterial and antibiofilm properties of traditional medicinal plant from Sheikh Buddin range.

During current project, antibacterial and antibiofilm properties of traditional medicinal plant Ziziphus nummularia leaf extract and various fractions was investigated. The plant leaves were dried and extracted using 90% methanol followed by sequential fractionation using liquid-liquid fractionation. The fractions of a diverse polarity including chloroform, n-hexane, methanol and ethyl acetate and aqueous extracts were obtained that was further analysed by using HPLC. The phytochemical screening indicated presence of saponins, triterpenes and flavonoids. During DPPH assay, the methanolic fraction presented highest activity (IC50 193.1µg/mL), followed by ethyl acetate (IC50 220µg/mL) and chloroform (IC50 263µg/mL) fractions respectively. During FRAP assay, FRAP value for Z. nummularia extract 20.43µM. Among fractions, ethyl acetate fraction presented highest FRAP value (370.2µM), followed by chloroform (204µM) and methanolic (249µM) fractions. The antimicrobial activity of chloroform fraction was significantly high against P. aureginosa (6mm), L. monocytogenes, S. aureus (5mm), K. pneumoniae, B. Subtillus and E. coli (4mm). The ethyl acetate part presented significant activity (MIC 4mg/mL) against S. aureus, B. Subtillus and L. monocytogenes. The total extract and fractions were further tested for MBC and the MBC for ethyl acetate fractions was 4mg/mL, whereas all other fractions exhibited MBC >10mg/mL. No activity was recorded against Aspergillus niger. During antibiofilm assay, n-hexane fraction presented highest inhibition (88%) followed by ethyl acetate (69%) chloroform (65%) fractions. It was concluded that Z. nummularia possess moderate antimicrobial and antibiofilm activities. Further a synergistic effect is suggested in formulation having Z. nummularia.