Journal of Pharmaceutical Innovation最新文献

This study presents an AI-driven pharmaceutical data analysis tool designed to streamline drug formulation and quality control processes. Built using R’s app framework, the application integrates advanced machine learning techniques, statistical analyses, and interactive visualizations into a user-friendly interface. Users can upload their own datasets, perform comprehensive exploratory data analysis (EDA), and generate actionable insights through predictive modeling and simulated real-time monitoring. The tool demonstrates proof-of-concept alert mechanisms designed to highlight potential anomalies and formulation trends, though these features are currently implemented in a simulated environment. Results from the analysis highlight critical factors influencing tablet hardness and disintegration time, such as excipients like Mannitol and Microcrystalline Cellulose, as well as physical properties like Angle of Repose and Bulk Density. Classification models achieve high accuracy (85.71%) and robust performance metrics, including sensitivity, specificity, and Kappa statistics. Regression models reveal challenges in predicting hardness due to complex interactions between variables. The ROC curve demonstrates excellent discriminatory power, underscoring the reliability of the classification model. This integrated approach empowers formulation scientists to prioritize key variables, address anomalies, and enhance product consistency. By combining AI-driven insights with interactive features, this tool bridges the gap between data science and pharmaceutical research, offering a scalable solution for optimizing drug development and manufacturing processes.

This research aimed to develop and characterize cisplatin-loaded chitosan nanoparticles (CHNPs) embedded in a mucoadhesive buccal film (MFs) for oral cancer treatment. CHNPs were prepared using the ionic-gelation method, while the MFs were formed by the film-casting technique. Box-Behnken design was used to examine the effects of independent variables on dependent variables and optimize the CHNPs. Optimized nanoparticles (OPNPs) showed particle size of 198.3 nm, polydispersity index of 0.181, zeta potential of + 26.2 mV, entrapment efficiency of 84.38%, and drug loading of 25.37%. Fourier transform infrared and Differential scanning calorimetry confirmed the cross-linking between chitosan (CH) and sodium tripolyphosphate and encapsulation of cisplatin within CHNPs. Scanning and transmission electron microscopes revealed the spherical shape with a smooth surface of CHNPs. MFs (CNF1–CNF5) were formulated after incorporation of OPNPs into plasticized solutions of CH, hydroxypropylmethyl cellulose, polyvinyl alcohol, and polyethylene glycol 400. CNF1 films demonstrated acceptable thickness, weight, drug content, pH, highest swelling index, folding endurance, moisture absorption, and retention time. SEM micrograph showed good dispersion, smooth and slightly wrinkled surface, with folded and curled edges. CNF1 films showed sustained drug release of 80.02 ± 0.74% over 16 h, with a slower, more controlled release pattern compared to OPNPs and cisplatin. CNF1 showed zero-order release kinetics and lower flux and permeability coefficient as compared to OPNPs and cisplatin indicating slower, more controlled drug release. IC₅₀ value against the human oral squamous cell carcinoma lines (HSC 3 cells) of CNF1, OPNPs, and pure cisplatin was 74, 141 and 175 µg/ml. This suggests that the CNF1 significantly enhanced the cytotoxic effect of cisplatin. The CNF1 also showed good storage stability at 40 ± 2 °C and RH 75 ± 5%, for three months. Therefore, MFs containing CHNPs are a promising approach for buccal delivery of cisplatin, especially in oral cancers requiring sustained drug delivery.

Purpose

Regulatory inspections ensure consumer safety and product quality. In tightly regulated industries, compliance and organizational improvement efforts must align to achieve operational excellence. This study examines how surveillance current good manufacturing practice (CGMP) inspections influence the relationship between quality management practices and a continuous improvement mindset at pharmaceutical manufacturing facilities.

Methods

The study builds on a regression analysis of pooled cross-sectional data from drug manufacturers and the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research (CDER), supplemented by ten interviews with operational excellence leaders.

Results

Quality management practices catalyze continuous improvement. Inspections may provide useful external nudges in this context; however, the results suggest that their frequency should be carefully planned. In particular, we observe that a moderate frequency of CGMP inspections has the potential to support quality management efforts, whereas longer frequencies show a negative interactive effect. CGMP inspections validate quality management improvements and foster further improvements; however, this effect decays over time.

Conclusion

Regulatory agencies must carefully plan their surveillance inspection scheduling. If more frequent surveillance inspections are not feasible, they should consider complementing them with other initiatives —such as the Quality Management Maturity program—to further support the enhancement of quality practices and extend the duration of their positive effects on manufacturers.

Sleep disorders, particularly those induced by sleep deprivation, pose significant challenges to cognitive function and overall mental health. Armodafinil (ADF), an R-enantiomer of modafinil, has demonstrated efficacy in enhancing wakefulness but is limited by poor water solubility and systemic side effects. This study explores the potential of intranasal Spanlastic nanovesicles (SNVs) as a brain-targeted delivery platform for ADF. Owing to their nanoscale size and high deformability, SNVs exhibit enhanced mucosal permeation and improved brain targeting compared to conventional intranasal delivery systems. A 3³ Box-Behnken statistical design was employed to optimize ADF-SNVs based on vesicle size (VS), zeta potential (ZPOT), and entrapment efficiency (EE). The optimized ADF-SNVs exhibited a VS of 189.62 nm, ZPOT of -37.14 mV, and EE of 82.71%. Besides, the optimized formulation exhibited controlled drug release and boosted permeation through the nasal membrane. Pharmacokinetic studies revealed significantly higher brain bioavailability of ADF following intranasal administration of ADF-SNVs thermogel, with a notable increase in the brain-to-blood concentration ratio (AUC_brain/AUC_blood = 0.68). Moreover, the intranasally administered ADF-SNVs thermogel demonstrated a 2.5-fold and 4.7-fold increase in brain bioavailability compared to the intravenously and intranasally administered ADF suspensions, respectively. Histopathological assessments confirmed the safety and tolerability of the formulation. These findings underscore the potential of Spanlastics-based intranasal delivery systems as an innovative, noninvasive strategy for brain-targeted drug delivery in managing sleep disorders.

Graphical Abstract

Background

Elephantopus scaber (E. scaber) is a medicinal plant frequently used in traditional medicine for its health-promoting properties, as it contains numerous physiologically active compounds. However, scientific research on the metabolite profile of this plant remains limited.

Purpose

This study aims to establish chemical profiles of E. scaber leaf extracted by different polarity solvents (hexane, chloroform, acetone and 70% (v/v) ethanol) and to correlate the chemical markers to anti-Vibrio activities using the ¹H NMR-metabolomics approach.

Methods

A portion of the powdered E. scaber leaf sample was extracted using different solvent systems, namely hexane, chloroform, ethyl acetate, and 70% (v/v) ethanol. Each extract was evaporated to dryness and subsequently lyophilized before being subjected to NMR analysis. For multivariate data analysis, all samples were prepared in six replicates.

Results

The application of principal component analysis effectively distinguished the extracts based on their metabolite profiles. Acetone and 70% (v/v) ethanol were determined to have good extraction efficiency. The findings from the partial least squares analysis revealed a significant correlation between the polar chemicals present in the acetone extract of E. scaber leaf and its anti-Vibrio activity. According to the loading plot, acetone extracts contain a more diversified spectrum as compared to the other extracts, with a total of 42 metabolites comprising carbohydrates, amino acids, flavonoids, terpenoids, organic and fatty acids.

Conclusion

The identification of these metabolites in E. scaber leaf extracts indicate that they may play a significant role in the anti-Vibrio action.

Purpose

Cefixime (CEF) demonstrates strong activity against Streptococcus pyogenes despite its limited dermal penetration and low drug bioavailability, as per Biopharmaceutics Classification System (BCS). The study aimed to develop a nanoparticle system designed for enhanced topical delivery of cefixime (CEF-NP) using hydroxypropyl methylcellulose (HPMC K100M) and a QbD-optimized formulation process.

Methods

A 2³ full factorial design and later Central Composite Design (CCD) optimization studied essential variables of CEF concentration, HPMC K100M concentration, and stirring speed. The risk assessment technique led to the identification of essential process parameters that strengthened the formulation. The process successfully optimized two main outcomes, such as entrapment efficiency (EE) and antibacterial activity (zone of inhibition, ZOI).

Results

The drug-polymer compatibility as well as uniform spherical particle shape was also confirmed by concerned evaluations. The optimized CEF-NP showed high drug encapsulation efficiency and superior anti-bacterial activity against S. pyogenes compared to pure CEF. Design space analysis and desirability function evaluation succeeded in validating the model after optimization.

Conclusion

This study aligns with the Sustainable Development Goals (SDGs) by advancing the development of optimized nanocarrier systems aimed at mitigating antimicrobial resistance, while simultaneously incorporating environmentally sustainable waste management practices. The developed CEF-NP formulation, demonstrates potential for the successful fabrication of an effective topical antimicrobial formulation.

Graphical Abstract

Background Allergic conjunctivitis is a chronic inflammatory eye condition that can persist year-round but typically peaks during spring and summer. Effective ocular drug delivery remains challenging due to rapid tear clearance and poor residence time.

Objective To develop and optimize a muco-adhesive ocular film incorporating Hibiscus rosa sinensis leaf mucilage together with gelatin and sodium carboxymethyl cellulose (SCMC) for sustained delivery of aceclofenac (ACK) to the eye.

Methods Thirteen ACK-loaded ocular film formulations were prepared based on a Box–Behnken design, varying amounts of SCMC, gelatin and Hibiscus mucilage. Each formulation was evaluated for physicochemical parameters (thickness, weight variation, drug content), pH, osmolarity, swelling index, disintegration time, mechanical strength (tensile strength and folding endurance), sterility, mucoadhesion time, and in vitro drug release. Statistical analysis (ANOVA) was used to assess the influence of polymer concentrations on mucoadhesion.

Results Film thickness ranged from 0.16 ± 0.01 to 0.21 ± 0.01 mm; weight varied between 64.84 ± 0.7 and 75.11 ± 0.7 mg; drug content spanned 87.15 ± 1.05% to 98.81 ± 2.15%. The optimized formulation (F8: SCMC 50 mg, gelatin 20 mg, Hibiscus mucilage 10 mg) achieved physiological pH (7.0 ± 0.1), acceptable osmolarity, and high mucoadhesion (636 ± 3.6 minutes). The films showed sustained drug release consistent with a zero-order, diffusion-controlled mechanism. Among formulations, F6 achieved the highest ACK permeation at 24 h (96.95 ± 2.36%), followed by F12 (96.21 ± 4.57%). Moisture uptake varied (highest in F6: 21.09 ± 0.7%; lowest in F5: 11.36 ± 0.8%). FTIR confirmed drug–excipient compatibility, and ANOVA modelling demonstrated a strong correlation (R² > 0.99) between polymer concentration and mucoadhesion performance.

Conclusions The developed mucoadhesive ocular films leveraging Hibiscus mucilage, gelatin and SCMC offer a sterile, stable, uniform-film platform with enhanced mucoadhesion, sustained drug release and high drug permeation. These characteristics make them a promising alternative to conventional ophthalmic dosage forms for treating ocular pain and inflammation.

Silkworm silk has gained recognition as a copious biopolymer with a number of alluring properties since it was initially found more than 4,000 years ago. Silk fibroin (SF), the primary protein found in silkworm silk, is utilized in several technical development processes, most notably tissue engineering and the production of biomaterials for drug delivery systems. Its applications are not limited to the textile industry. Despite its beneficial curative effects, traditional Chinese medicine (TCM) has several disadvantages, such as complex ingredients, unstable medications, potential drug interactions, and more.Developing a unique drug delivery method that can load Chinese medicine monomers (CMM) is critical to resolving this issue. By employing SF as a carrier material to transport CMM, innovative CDDS that considerably improve sickness treatment without incurring harmful side effects can be developed. To assess and evaluate new research findings and successes, a study of silk fibroin as a loading CMM carrier material is important. Our work thoroughly investigates and assesses recent research on novel medication delivery methods based on SF and TCM monomers. Recently, SF’s outstanding mechanical properties—such as ease of manufacture, excellent biocompatibility, controlled biodegradation, and customizable fictionalization have enabled cutting-edge applications. This review examines the structure, content, fundamental qualities, and relationship between structure and attributes in science fiction, as well as a brief explanation of procedures for making and modifying diverse materials. Furthermore, we address our future plans for SF-based materials in TCM biologic delivery, gene therapy, wound healing, and bone regeneration applications.

Graphical Abstract

Applications of Silk Fibroin

Background

The current research aimed to formulate and evaluate Metoprolol succinate-containing minitablets. Preliminary batches of sustained-release minitablets were formulated, the factorial design was employed, and quality by design was applied to formulation.

Methods

A full 3² factorial design was applied for preparing minitablets using the direct compression method and varying concentrations of glyceryl behenate and HPMC K100M. Pre- and post-formulation characteristics were assessed. Different formulation parameters were evaluated for both drugs and formulations. A stability study was performed for 6 months, and the optimized batch was compared with the marketed formulation.

Results

The results exhibited no appreciable interactions between drugs and excipients during the preformulation study. Thus, it can be predicted that there was compatibility between the drug and excipients. Formulation F1, which has 2.5% HPMC K100M and 40% glyceryl behenate and follows zero-order release kinetics, was intended to be the best formulations. The quality of the formulation can be maintained by controlling the critical parameters in accordance with the results.

Conclusion

The formulated minitablets remained stable for six months, and the results point to Metoprolol minitablets as a potentially useful technology for a controlled-release drug delivery system utilizing glyceryl behenate and HPMC K100M.