Journal of Pharmaceutical Innovation最新文献

Purpose

The study aims to critically review US FDA warning letters (WLs) issued during inspections between 2019 and 2024 for compliance with Good Laboratory Practice in Preclinical research facilities.

Methods

WLs were downloaded from the US FDA public domain of the WLs and the content of each WL was assessed based on types and frequencies of violations and corrective and preventive actions (CAPA) employed by the testing facility or requested by the FDA investigators. Each WL was evaluated and critically analyzed about the applicable regulation. Violations were correlated with consequences of non-compliance, as addressed by the FDA inspectors.

Results

Eight WLs letters were analyzed. The incidence of violations concerning the QAU’s failure to meet responsibilities, documentation deficiencies, noncompliance with study protocols, deviations in animal handling, and data capture in the final study report was 12% each. The violations concerning the study director’s failure to fulfil his/her duties and deficient/ noncompliance to pertinent SOPs were 10% each. The incidence of inadequate qualifications among study personnel and the management of specimens/reagents and controls was 9% and 6%, respectively. The minimal variance was linked to specimen/record retention (5%).

Conclusion

Testing facilities in preclinical research are requested to evaluate personnel responsibilities, improve GLP training programs, and implement adequate standard procedures to comply with GLP standards, reducing the recurrence of these violations and enhancing data integrity and validity that will support a clinical submission.

Purpose

Xiaoyao San (XYS) is an ancient clinical dosage form in China. Our previous research discovered that the compound decoction of traditional Chinese medicine presents a mixed-phase system, encompassing nanophase, precipitated phase, suspension phase, and true solution phase. Hence, this study is intended to screen out the effective phases among the four phases of XYS and explore its anti-hyperplasia effect on mammary glands.

Methods

Four phases of XYS were prepared by centrifugation-dialysis. The preparation process, characterization, determination of chemical composition, and anti-breast hyperplasia effects were investigated.

Results

The four phases of XYS were successfully separated. The characterization results indicated that the nanophase of XYS had the smallest particle size, polydispersity index (PDI) value, and the largest potential value, with an average particle size of approximately 100 nm. In the content determination, the component content ratios of the four phases were consistent, and the content of the nanophase was much higher than that of the other phases. The pharmacodynamic results demonstrated that all indicators of rats in the XYS whole liquid and nanophase groups were significantly improved compared with those in the model group (p < 0.05). At the same time, there were no significant differences in the indicators of rats in the other phase groups. The grey correlation degree analysis revealed that the common peaks of both XYS whole liquid and nanophase were correlated with the pharmacological effect, and the correlation degrees were all greater than 0.7.

Conclusion

This research successfully proved from physicochemical characterization and pharmacodynamics perspectives that the nanophase is the effective phase and that multiple components jointly exert the anti-hyperplasia effect of mammary glands.

Purpose

The aim of this present study is to develop and optimise a self-nano emulsifying drug delivery system (SNEDDS) for the enhanced oral delivery of dolutegravir (DTG), a poorly water-soluble antiretroviral drug.

Methods

The SNEDDS formulation was developed using Capmul MCM (oil), Kolliphor RH40 (surfactant), and PEG 400 (co-surfactant). Box Behnken design was employed to optimize the composition of the SNEDDS formulation. The prepared formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential, self-emulsification time, and in vitro drug release.

Results

The optimized SNEDDS formulation (F2) exhibited a droplet size of 79.2 ± 0.9 nm, PDI of 0.105 ± 0.012, zeta potential of -32.1 ± 1.5 mV, and self-emulsification time of 22 ± 2 s. In vitro drug release studies demonstrated a significantly higher cumulative drug release from the optimised SNEDDS formulation (98.9 ± 0.9% in 60 min) than pure DTG (42.5 ± 2.1%). The optimized formulation exhibited excellent thermodynamic stability and robustness under various stress conditions. Ex vivo drug release studies using rat stomach tissue confirmed the enhanced drug release potential of the optimized SNEDDS formulation in the gastric environment.

Conclusion

The developed SNEDDS formulation offers a promising approach for the enhanced oral delivery of DTG, potentially improving its bioavailability and therapeutic efficacy.

Purpose

Artificial intelligence (AI) platforms are among the most prominent digital innovations in the contemporary time. The colossal growth and success of AI has garnered the attention of the scientific community and it is also being accepted in the public domain. The current review aims to provide in depth information about the utilization of AI in the pharmaceutical sector along with the limitations, ethical-legal aspects and future perspective of this technology in uplifting the growth of this sector.

Methods

The accredited web pages of PubMed, Google Scholar, Scopus and Web of Science were accessed using the terms “artificial intelligence” and “pharmaceutical”. Cross-referencing important articles yielded additional references which were evaluated and utilized for inclusion in writing this review.

Result

The dexterity of AI tools was explored in numerous domains of pharmaceutical sector like drug discovery, pharmaceutical product development, manufacturing, product management, clinical & diagnostic field, 3D printing technology and community pharmacy. It was found that the augmentation of AI with pharmaceutical sector will lift the growth of this sector by heaps and bounds for the reason that every facet will be reshaped in terms of finances and time.

Conclusion

Significant developments in AI offers a revolutionary chance for drug discovery, formulation, clinical and diagnostic applications, 3D printing and plentiful applications in the pharmaceutical industry. However, AI presents risk factors and ethical concerns that must be handled before society, health systems, and individuals can fully benefit from it. Pharmaceutical developers should ensure that the AI tools and procedures comply with all ethical and regulatory standards enforced by the regulatory agencies.

Purpose

Breast cancer (BC) remains the leading cause of cancer-related mortality among women. This study aimed to improve the solubility, stability, and therapeutic efficacy of Resveratrol (RES) by developing an electrospun nanofiber mat for targeted drug delivery to breast tissue.

Methods

RES was incorporated into an inclusion complex with sulfobutylether β-cyclodextrin (SBE-β-Cyd) and polyvinylpyrrolidone (PVP K90). Polymer selection was guided by molecular docking and solution-state stability studies. The nanofibers were characterized using FTIR, DSC, XRD, and SEM, and evaluated for entrapment efficiency, moisture content, contact angle, and tensile strength. In vitro and ex vivo studies assessed drug release in phosphate buffer (pH 7.4) and biocompatibility using the HET-CAM assay. Antioxidant activity was analyzed via the DPPH assay, while anticancer potential was tested against MCF-7 breast cancer cells.

Results

The nanofibers demonstrated sustained RES release, enhanced solubility, and improved skin permeation. Biocompatibility studies confirmed their non-irritant nature and antioxidant assays showed maintained activity. Cytotoxicity assays indicated that RES-loaded nanofibers exhibited significant anticancer effects against MCF-7 cells, surpassing pure RES.

Conclusion

The developed RES-loaded nanofiber mat presents a promising localized treatment for breast cancer by overcoming RES’s solubility and stability limitations. The formulation enables sustained drug release and enhanced therapeutic efficacy, warranting further in vivo investigations to validate its clinical potential.

Purpose

The study aimed to develop liquid dressings containing copper nanoparticles infused with vanillic acid to enhance their antibacterial properties.

Method

PEG 6000 served as a stabilising agent in the chemical reduction process. The Box-Behnken design was employed to optimise the synthesised nanoparticles. Vanillic acid, obtained from Vanilla planifolia, possesses medicinal qualities, promoting wound healing and antioxidant properties. The nanoparticles were integrated into an optimised batch of in-situ film (liquid dressing) and assessed using DSC, FESEM, cytotoxicity analysis, and in-vivo testing.

Result

The optimised batch exhibited an entrapment effectiveness of 90.9%, an in-vitro drug release of 89.6%, a particle size of 97.9 nm, a zeta potential of -31 mV, and a polydispersity index of 0.316.

Conclusion

The liquid dressing exhibited superior wound healing capabilities compared to the pure Vanillic acid solution.

Graphical Abstract

Objectives

Bacterial vaginosis (BV) is a common condition among women of reproductive age. Short-term antibiotic treatments are often clinically effective, but recurrence after treatment is frequent. The high recurrence rate and increasing antibiotic resistance highlight the need for new treatment methods. This study aimed to evaluate the effectiveness of a vaginal gel containing Rheum turkestanicum Janisch in comparison to metronidazole for the treatment and prevention of BV recurrence.

Study Design

This study was a randomized, triple-blinded, controlled trial involving 30 women. Married women aged 18 to 50 years who had been diagnosed with BV and did not meet any exclusion criteria were randomly allocated to the intervention or control groups. The intervention group received R. turkestanicum vaginal gel and R. turkestanicum capsules, while the control group received metronidazole vaginal gel and placebo capsules. Both groups underwent treatment for 7 days.

Main Outcome Measures

Variables such as demographic data, bacterial vaginosis patients’ signs and symptoms, Amsel’s criteria, and Nugent score were compared and examined before and after treatment with rhubarb and metronidazole in the patients.

Results

The initial assessment, conducted 10 days after treatment, showed significant improvement in each control and treatment group, but there was no significant difference between the two groups. However, the evaluation of recurrence status 30 days later indicated that the intervention group (using R. turkestanicum vaginal gel and R. turkestanicum capsules) was significant to metronidazole in treating recurrence.

Conclusion

Rheum turkestanicum has the potential to be offered as a novel treatment for BV.

Purpose

The study aimed to develop naringin (NAR)-loaded microbeads coated with Eudragit-S100 polymer for colon-targeted drug delivery, focusing on effectively treating inflammatory bowel disease (IBD).

Methods

NAR-loaded microbeads were formulated by ionic gelation technique. The formulation variables (concentration of chitosan, sodium alginate and sodium tripolyphosphate) were optimized by using Box-Behnken's Design (BBB). Morphological and characterization of the microbeads were performed. Additionally, the therapeutic potential of the microbeads was evaluated in the acetic-acid-induced colitis model by assessing colitis severity, inflammatory markers and histological examination of colonic tissue.

Results

The optimized formulation exhibited a particle size (PS) (258.42 ± 2.98 µm), drug entrapment efficacy (DEE) (87.04 ± 1.67%), % yield (88.45 ± 2.87%), swelling index (SI) (1.21 ± 0.08) in pH 7.4, and zeta potential (-26.24 ± 0.21 mV). Maximum drug release (93.07 ± 3.67%) was achieved in simulated colonic fluid at pH 7.4 over 24 h, following a non-Fickian mechanism involving diffusion, matrix erosion, and bacterial degradation. The results demonstrated that optimized formulation significantly alleviated colitis symptoms by reducing oxidative stress and inflammatory cytokines in colon tissue.

Conclusion

NAR-loaded microbeads, optimized by Box–Behnken design, showed strong therapeutic potential in an acetic acid (AA)-induced colitis model. They reduced tissue necrosis factor-α and myeloperoxidase while improving antioxidant levels such as catalase and superoxide dismutase, offering a promising targeted therapy for IBD.

Objective

The purpose of this research was to investigate the effects of Citrus maxima and its inclusion complex on neuropharmacological diseases, such as depression and anxiety, and its potential mechanisms.

Materials and methods

The essential oil (EO) was extracted and collected using a Clevenger apparatus. A gas Chromatography-Mass Spectroscopy (GCMS) study was performed to analyze the chemical constituents of EO. The Inclusion complex was prepared using the paste complexation technique and its characterization was done by Karl Fisher Titration (KFT), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Swiss albino mice about 3 months old, were purchased from the establishment of Environment Controlled Facilities. Behavioral tests conducted were the Open Field Test (OFT), Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Forced Swimming Test (FST).

Results

The SEM, XRD, and KFT analysis shows that the inclusion complex formed by using the essential oil and β-CD shows significant results in forming complexation, that helps in proper entrapment of the essential oil thus protecting it from various environmental factors. After conducting the toxicity study, behavioral studies as well as the neurochemical examinations it is concluded that the Citrus maxima essential oil used in a concentration of 100 mg/kg along with its inclusion complex used in the concentration of 50, 100 mg/kg shows significant results.Mechanism of action shows the involvement of GABA and serotonin to be the neurotransmitters associated with the study.

Conclusion

EO extracted from the peel of Citrus maxima and its inclusion complex demonstrates strong neuropharmacological effects on anxiety and depression models in mice, indicating the involvement of GABAergic and serotonergic pathways.

Graphical Abstract

Curcumin, a natural polyphenol derived from turmeric, holds significant promise for breast cancer treatment due to its diverse pharmacological properties, which include antioxidant, neuroprotective, anti-inflammatory, and anti-amyloid effects. However, its clinical application is limited by its poor solubility and low bioavailability. The objective of this study is to develop a novel drug delivery system using citric acid (CA)-functionalized carboxylated (COOH) Multi-Walled Carbon Nanotubes (MWCNTs) to enhance the solubility and bioavailability of curcumin for effective breast cancer treatment. The formulation of curcumin-loaded MWCNT-COOH-CA was optimized using a Box-Behnken design. The characterization of curcumin-loaded MWCNT-COOH-CA incorporated evaluations of particle size, zeta potential, and % entrapment efficiency. Furthermore, the formulation underwent in vitro release and cytotoxicity assessments. The optimal formulation exhibited a particle size of 371 nm, a zeta potential of -25.2 mV, and an entrapment efficiency of 77.86%. In vitro release study demonstrated a pH-dependent release pattern, with enhanced release under acidic conditions simulating the tumor microenvironment, which showed a cumulative release of 93.48% at pH 5.5 as compared to 91.24% at pH 7.4 at the 24-hour time point. The formulated product exhibited significant cytotoxic activity against MCF7 breast cancer cells, with an IC₅₀ value of 30.82 µg/mL, and demonstrated efficient cellular uptake. The novel curcumin-loaded MWCNT-COOH-CA demonstrated potential as an efficacious and targeted approach for the treatment of breast cancer.