Experimental and in silico evaluation of Carthamus tinctorius L. oil emulgel: a promising treatment for bacterial skin infections.

Purpose: The current study aimed to develop a topical herbal emulgel containing Carthamus tinctorius L. (CT) oil extract, which has been scientifically proven for its antibacterial and antioxidant activities for the ailment of bacterial skin infections. Method: The CT emulgel was formulated by response surface methodology (RSM) and was evaluated by various parameters like extrudability, spreadability, pH, viscosity, and antibacterial and antioxidant activities. Molecular docking was also performed using AutoDock. Results: Among all formulated CT emulgels, F9 and F8 were optimized. Optimized formulations had shown good spreadability and extrudability characteristics. Sample F8 had % inhibition of 42.131 ± 0.335, 56.720 ± 0.222, and 72.440 ± 0.335 at different concentrations. Sample F9 had % inhibition of 26.312 ± 0.280, 32.461 ± 0.328, and 42.762 ± 0.398 at concentrations of 250 µg/ml, 500 µg/ml, and 1,000 µg/ml, respectively, which shows that both samples F8 and F9 have significant antioxidant potential. Optimized CT emulgels F8 and F9 had significant antibacterial activity against Staphylococcus aureus and Escherichia coli at p-value = 0.00, the Emulgel-F8 shows zone of inhibition of 24 mm for E-coli and 19 mm for S-aureus. Emulgel-F9 shows zone of inhibition of 22 mm for E-coli and 15 mm for S-aureus while pure CT- Oil extract shows zone of inhibition of 25 mm for E-coli and 20 mm for S-aureus and ciprofloxacin used as standard shows 36mm zone of inhibition against both E-coli and S-aureus. The comparative investigation through molecular docking binding affinities and interactions of ligands with various target proteins provides insights into the molecular processes behind ligand binding and may have significance for drug discovery and design for the current study. Conclusion: The current study suggests that C. tinctorius L.-based emulgel has good antioxidant and antibacterial activities against E. coli for the treatment of bacterial skin infections.

Formulation development and evaluation of transdermal emulgel using Aloevera extract and natural penetration enhancers.

This study was to formulate Aloevera extract loaded emulsion (O/W) based gels, by using various concentrations of rose oil, olive oil and Lemon oil as natural penetration enhancers for transdermal effect to treat skin problems. By using RSM, Aloevera emulgels were formulated and then optimized. Stability studies, physico-chemical characteristics, spreadability, skin protection factor, thermal analysis, FTIR, antimicrobial activity, in vitro drug release study (at 37ºC with 100 rpm for 180 minute in release medium at pH 5.5) and in vivo skin evaluation tests were performed. The results were then statistically analyzed. Among all formulations, G12 has shown maximum 93.53% Aloevera release at higher concentration of Olive oil with decreased concentration of Rose oil and Lemon oil. Analysis of variance (ANOVA) was conducted to evaluate the results exhibited independent variables have remarkable effects on dependent variables. Contour plot is also drawn to express the response between independent and dependent variables. All formulations have followed Korsmeyer-Peppas kinetic model. In summary, the combination of penetration enhancers in Aloevera emulgel can be successfully utilized for treatment of mild-moderate acne vulgaris and other skin problems, as optimized emulgel has shown good permeability, prolonged residence time on skin surface and proved good anti-microbial activity.

Synthesis and characterization of self-assembling chitosan-based nanoparticles.

Chitosan (CHT) based biodegradable nanovectors were synthesized and modified with poly ethylene glycol 4000 (PEG-4000). CHT having medium molecular weight with 75% to 85% deacetylation was phthaloylated with phthalic anhydride, followed by PEGylation using PEG-4000. After confirmation of successful PEGylation by fourier transforminfra red spectroscopy (FTIR), the modified polymer was further processed to develop the nanocarrier using ionic gelation method by the addition of sodium tripolyphosphate (NaTPP). The prepared nanocarriers were subjected to physicochemical evaluation. The surface morphology of the particles was observed under scanning electron microscope (SEM), and particle size by dynamic light scattering (DLS) method, which was about 159-170nm in diameter. The zeta potential of the prepared nanovectors was +0.907mV which was due to cationic nature of nanovectors. The cell viability studies were also conducted to find the suitability of the carrier for in-vivo application, using liver cancerous cells (Hep G2). The findings have disclosed the concentration dependent activities of the particles, as viability of the cell was shown to be decreased with the increase in the concentration of the particles. Conclusively, the study was successful in determining the toxicity profile of these nanovectors as these were proved non-toxic at specific concentration.

Development of grape seed extract based formulations by using non-invasive biophysical technique and its impact on skin aging.

Given the substantial benefits of grape seed extract (GSE) in reducing oxidative stress, the study aimed development, characterization and comparative analysis of GSE-based formulations. The development entailed extraction of GSE from Vitisvinifera L. HPLC confirmed catechin, epicatechin, gallic acid, epicatechingallate and procyanidin dimers. Storage of Formulations observed, Stability & rheological parameters determined. Olive oil used as a permeability enhancer. Presence of the highest oleic acid content (65-86%) in Olive oil, skin permeability within the stratum corneum was enhanced hence better transdermal skin absorption. Using two-way ANOVA, and T-test, efficacy of formulations and impact on slowing down skin aging by countering exogenous factors of oxidative stress determined. Non-invasive biophysical technique showed emulgel substantially reduced roughness, scaliness, winkles, and sebum content by 55%, 26%, 23.9% and 30.3% respectively enhancing elasticity and hydration by 50% and 32.2% respectively. Emulsion reduced roughness, scaliness, winkles and sebum content 14%, 13%, 21% and 26.13% respectively enhancing elasticity and hydration 45.3% and 29.85% respectively. The formulations significantly offset exogenous factors of aging and impact on free radicals and oxidative stress and may be safe to incorporate bio-active botanical antioxidants for evaluation of derma cosmetic benefits in management of dehydrated and aged facial skin.

Synthesis and in vitro characterization of chlorpheneramine-laden liposomes for topical applications.

This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.

Evaluation of Pharmacokinetic Interaction of Cilostazol with Metoclopramide after Oral Administration in Human.

BACKGROUND: Metoclopramide is mainly metabolized by CYP2D6, CYP3A4, CYP2C19, and CYP1A2 enzymes, while cilostazol is also metabolized by CYP3A4, CYP2C19, and CYP1A2 enzymes. AIM: This study evaluates the effect of cilostazol on the pharmacokinetics of oral metoclopramide. METHODS: This was a randomized, two-phase cross-over pharmacokinetic study separated by a 4-week wash-out time period, 12 healthy non-smoking volunteers received metoclopramide 20 mg as a single oral dose and after 4 weeks, cilostazol 100 mg twice daily for 4 days then with metoclopramide 20 mg on test day. Serial blood samples were analyzed by using a validated high-performance liquid chromatography-ultraviolet method to determine maximum plasma drug concentration (Cmax), time to reach (Tmax), and area under the curve (AUC0-∞) of metoclopramide. RESULTS: Cilostazol increased the mean Cmax, AUC0-∞ and half-life (T1/2) of metoclopramide by 6%, 27% and by 0.79 %, respectively. In addition, Tmax of metoclopramide was delayed by cilostazol. CONCLUSION: The results showed delayed Tmax of metoclopramide by cilostazol, which could lead to the conclusion that cilostazol affects the absorption of metoclopramide. Both drugs when necessary to administer together must not be administered at the same time especially when given in gastroparesis patients.

RP-HPLC based method for the determination of Tamsulosin HCl in API, Prepared dosage form and spiked plasma.

An analytical method for measurement of tamsulosin HCl from its different life cycle stages was developed using RP-HPLC technique. The elution of tamsulsoin was studied using MediterraneaTM Sea 18 column (dimesions 250 × 4.6 mm and pore size 5µm) and mobile phase comprising of buffer (pH 5.4): Acetonitrile (ACN) at ratio 60:40. The tamsolusin HCl elution was also studied by varying the operating conditions including the composition and flow rate of mobile phase, stationary phase temperature and scanning wavelength. The optimal elution conditions include; a) mobile phase flow rate; 1ml/min, b) wavelength; 224nm and stationary phase temperature 30°C. Linearity was recorded in the absorption data over tamsulosin concentration range of 0.007 to 40µg/ml. The values of paramters LOD and LOQ noted for tamsulosin dissolved in mobile phase were 0.0014 and 0.042µg/ml respectively, while for the counterpart in spiked plasma were 0.0017 and 0.051µg/ml respectively. The analytical method was prompt, accurate, reproducible and suitable for analysis of tamsulosin HCl in different samples of interest at formulation, regulation and clinical evaluations.

Formulation study of topically applied lotion: in vitro and in vivo evaluation.

INTRODUCTION: This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA) as a locally applied analgesic lotion. METHODS: To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v) of permeation enhancers, namely propylene glycol (PG) and turpentine oil (TO). These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability), in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. RESULTS: It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 µg.cm(-2).min(-1) and 0.67 ± 0.02 µg.cm(-2).min(-1) for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05) from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively). CONCLUSION: It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.