The current research work describes the development of a rapid HPLC method for the concurrent detection of pregabalin and piperine in dual drug‐loaded nanoformulations. The primary goal was to recognize the chromatographic conditions wherein propitious segregation of the integrants with quality peaks can be attained. An attempt to expound the target analytical profile was made to accomplish this goal, and critical method attributes (CMAs), viz. percentage acetonitrile content, injection volume and pH, which affect critical quality attributes (CQAs), were identified using systemic risk analysis. Box–Behnken design was employed to develop a relationship between CMAs and CQAs, which engenders an analytical design space. Efficient chromatographic separation for pregabalin and piperine was attained using an analytical C18 column and mobile phase comprising acetonitrile–water (pH 6.9; 70:30%, v/v) in an isocratic elution mode with a 1 ml/min flow rate. The elution was descried at an isosbestic wavelength of 221 nm using a photodiode array detector. The International Conference on Harmonization guidelines were adopted for the developed HPLC method. The validated HPLC method can be further utilized for the simultaneous quantification and detection of pregabalin and piperine in other lipid‐based nanopharmaceuticals such as polymeric nanoparticles, nanocrystals, solid‐lipid nanoparticles, metallic nanoparticles, etc., in in vitro and in vivo studies.

The present research study limns the preparation of MNF loaded transethosomes (MNF-TE) to improve MNF solubility, bioavailability and permeation through skin layers for transdermal delivery. MNF-TE was formulated using thin-film hydration method and optimization was done using Box-Behnken design (BBD). MNF-TEopt was characterized for Polydispersity index (PDI), vesicle size, entrapment efficiency, zeta potential and in vitro MNF release. For further evaluation, Pharmacokinetic study, Transmission electron microscopy (TEM), Skin permeation study and Confocal scanning laser microscopy (CLSM) were performed withal. The MNF-TEopt presented spherical and sealed shape vesicles with small vesicle size of 148.6 nm, entrapment efficiency of 74.23%, PDI of 0.1139 and in vitro release of 65.32%. The CLSM study unveiled that the developed formulation has greater permeation of MNF across the skin layers in comparison with the MNF suspension gel. The pharmacokinetic study demonstrated C max and AUC 0-24 h of 6.94 ± 0.51 μg/ml and 43.92 ± 7.90 μg.h/ml via transdermal route in comparison to C max and AUC 0-24 h of 3.74 ± 1.91 μg/ml and 22.96 ± 9.76 μg.h/ml presented by MNF-TE oral administration. The in vivo study revealed that the MNF-TE gel has good anti-arthritic potential in comparison with the standard diclofenac gel which was evinced by radiographic analysis and histopathological studies. Further, skin irritation study on Wistar albino rats confirm that the developed MNF-TE formulation is safer for skin application. The current investigation corroborated that the prepared TE vesicle formulation is a treasured carrier for the MNF transdermal delivery for the management of rheumatoid arthritis.

Background: Onychomycosis, the most prevailing affliction of the nail, accounts for approximately 90% of the toenail infection worldwide. Owing to this infection, the affected patients experience reduced quality of their life as its awful appearance undermines their daily activities and social interactions. Onychomycosis is notoriously strenuous to cure. Systemic therapy, though effective, possess severe complication of toxicities, contra-indication, and drug-drug interaction. Albeit topical therapy is favorable to its localized effect, its potency relates to the effective concentration of the antifungal drugs achieved at the infection site. An approach to accomplish this goal would be acquiring benefits from the terpenes as penetration enhancers from natural sources. This investigation aimed to study the effectiveness of six terpenes, namely safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, as potential penetration enhancers for improved nail permeation of fluconazole through the human nail.Methods: Ex vivo permeation experiments were carried out by soaking the nail clippings of human volunteers in control and working solutions containing fluconazole (5 mg/ml) per se and fluconazole (5 mg/ml) with 6% of each terpene, including safranal, lavandulol, rose oxide, 3-methyl-2-butene-1-ol, linalool, and limonene, respectively, for 48 h. The amount of fluconazole in nail clippings was quantified using an HPLC method.Results: Statistical analysis showed that fluconazole transungual permeation was influenced by the studied terpenes in the following order: safranal >lavandulol acetate >limonene > rose oxide (p-value >0.05) while the other terpenes showed no significant difference with the control group and safranal represents as the most effective permeation enhancer for the transungual delivery of fluconazole. Conclusion:It is concluded that the safranal can be successfully used as a safe and potential permeation enhancer to enhance the transungual delivery of fluconazole for the treatment of onychomycosis.

A simple, accurate, precise, and specific high-performance thin-layer chromatography (HPTLC) method for the quantitative determination and validation of baicalin in different extracts of Oroxylum indicum has been developed for the first time. The mobile phase of acetone‒ethyl acetate‒water‒formic acid (2:10:0.5:0.5, V/V ) was used for achieving good separation. Densitometric determination was carried out at 318 nm. The calibration curves were found to be linear in the range between 200 and 1000 ng per spot. During the analysis, the ethanolic extract of O. indicum showed higher content of baicalin than acetone, DMSO, and DMF extracts. Further, the antioxidant potential of different extracts of O. indicum were assessed with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The developed method of HPTLC was validated for specificity, accuracy, precision and linearity. The ethanolic extract has unveiled significant antioxidant activity with a percentage inhibition of 67.34%. Graphic Abstract

Background: Naringin, a bioflavanoid possessing multifaceted pharmacological properties present in Citrus sinensis peel. Our research demonstrates the process parameter at which high yield of naringin can be extracted from Citrus sinensis peel in "one run." Objectives: The study compares the efficacy of different modern and conventional methods for naringin extraction. Box-Behnken Design (BBD), was availed for optimization of process parameters for the extraction of naringin from Citrus sinensis peels. Materials and Methods: Extraction conditions (extraction time, solvent-to-drug ratio and extraction temperature) were optimized by Quality by Design (QbD), specifically BBD. Quantification analysis of naringin in different extracts was done using HPLC. Further, the antioxidant potential of different extracts of C. sinensis were assessed with the DPPH method. Results: Ultrasound-assisted extraction method gives the highest yield of naringin and ethanol found to be the most effective extractive solvent. Through the use of BBD, the optimal conditions for naringin extraction were established as extraction temperature-65.508°C, solvent-to-drug ratio-25.880 mL/g and extraction time-29.978 min. Under such conditions, naringin was yielded as 2.021 mg/g, which was nearly contiguous to the predicted value of 2.20 mg/g. The ethanolic extract has unveiled significant antioxidant activity with a percentage inhibition of 71.54%. Conclusion: The Ultrasound-assisted extraction method stood out to be the best amongst all the other thermal and non-thermal modes of extraction used, and ethanol was proved to be the most efficient extracting solvent. Furthermore, naringin extraction was significantly affected by all three different variables. The present work highlights the use of QbD, a multivariate statistical technique in the extraction field of therapeutically potent phytoconstituents, which makes the optimization method less laborious and time-saving than the traditional optimization method.