Journal of Pharmaceutical Innovation最新文献

Purpose

This study aims to enhance the targeting of erlotinib by grafting saccharides—galactose, pectin, and chitosan via oxalyl chloride-mediated processes. The objective is to evaluate the potential of these saccharide derivatives as ligands for targeted drug delivery, particularly to improve therapeutic efficacy in cancer treatments.

Methods

Saccharides (galactose, pectin, and chitosan) were chemically grafted onto erlotinib, forming conjugates. Characterization was conducted using 1H NMR, differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FTIR). The conjugates’ drug delivery efficiency was tested using A549 cell lines to assess their efficacy in targeting cancer cells.

Results

Characterization confirmed the successful grafting of saccharides onto erlotinib, as evidenced by 1H NMR, DSC, and FTIR. The in vitro drug release study demonstrated enhanced targeting efficiency of the saccharide-erlotinib conjugates, with improved cell-specific distribution and potential therapeutic benefits.

Conclusions

Grafting saccharides onto erlotinib offers a promising approach to enhance drug absorption, reduce degradation, and minimize side effects in cancer therapy. This targeted drug delivery strategy represents a significant advancement in biomedical engineering for optimizing cancer treatment efficacy.

This case study describes the development of a comprehensive drug-drug interaction (DDI) education initiative for nirmatrelvir/ritonavir (Paxlovid™) during the COVID-19 pandemic. Following Emergency Use Authorization in December of 2021, the rapid dissemination of information on identification and management of DDIs was needed to ensure appropriate use of nirmatrelvir/ritonavir when treating patients with COVID-19 who were at an increased risk of progression to severe illness. The initiative included comprehensive outreach activities to compliantly inform healthcare providers and patients through the development of various educational materials and omnichannel engagement strategies. This case study may serve as an example to guide best practices for therapeutics requiring timely and comprehensive approaches to the dissemination of medical information in the future.

Purpose

Despite stringent regulations enforced by the United States Food and Drug Administration (USFDA), numerous drug products still enter the market without adequate assurance of safety and efficacy, resulting in frequent recalls. To explore the real picture of such recalls, this analysis focuses on the USFDA drug recalls with a glance at medical devices, food products, biological products, cosmetics, tobacco products, and veterinary products from 2019 to 2023. The research aims to quantify and categorize these drug recalls, examining various contributing factors to recommend strategies for minimizing future recalls. Additionally, it investigates the influence of global and national crises, such as the COVID-19 pandemic, on the USFDA’s drug recall process.

Methods

Data from USFDA Enforcement reports were collected and sorted, and descriptive statistics were used to analyse drug recalls.

Results

Between 2019 and 2023, the USFDA documented 31125 recalls, of which 6217 involved drug products from 593 different companies. These recalls are frequently initiated by the companies themselves, with primary causes including sterility assurance failures, contamination, and improper storage conditions.

Conclusions

Drug recalls are a double-edged sword: while they are essential for protecting public health, they can also disrupt supply chains and lead to drug shortages, especially when there are no alternatives available. To prevent such disruptions, strict adherence to current Good Manufacturing Practices, along with comprehensive internal audits and rigorous USFDA inspections are vital for manufacturers to maintain quality standards and minimize the risk of recalls.

Purpose

The delivery of herbal medications is currently a growing area in pharmacy. One of the areas of interest for the scientists conducting pharmaceutical research is the use of floating drug delivery system (FDDS) for herbal medicine. In this study, we developed an oral herbal gastro-retentive in-situ gel using extracts from Azadirachta indica and Piper longum Linn, employing the quality by design (QbD) approach.

Methods

For the formulation and optimization of an oral herbal in-situ gel, a central composite design (CCD) was used. This design is based on 2-level factorial designs that have been supplemented with center and axial points to match quadratic models. The amounts of two independent variables, gellan gum (X1) and calcium carbonate (X2), were altered at five distinct levels. For the current investigation, the response variables viscosity (Y1), floating lag time (Y2), and gelling time (Y3) were used. According to DoE software, a total of 13 formulations were prepared by changing the gellan gum and calcium carbonate concentrations.

Results

The optimized formulation (OF2), which contains gellan gum 0.293% & calcium carbonate 0.706, satisfies the requirements of quality target product profile (QTPP) and critical quality attributes (CQA) for oral herbal in-situ gel with 75% and 73% drug content. OF2 had a 35.5 s gelling time, a 53 s floating lag time, and a viscosity of 53 cps. The formulated oral herbal in-situ gel exhibited stability for over 2 months under both freezing (-4 °C) and 40 °C with 60% relative humidity (RH) storage conditions.

Conclusion

The developed formulation presents a promising and innovative approach to enhance the gastric retention of herbal extracts, ultimately amplifying their therapeutic efficacy. This paper establishes the foundation for future preclinical and clinical studies on an oral herbal in-situ gel containing long pepper and neem leaf extracts for the treatment of peptic ulcer disease (PUD).

Purpose

Fast-disintegrating dosage forms based on nanofibers hold promise as effective carriers for a diverse array of drugs. In this study, our objective was to evaluate the effect of polymer polyvinylpyrrolidone (PVP) concentration on the disintegration time and drug release behavior of fast dissolving mats containing P. latifolia leaf extract.

Methods

To accomplish this goal, we created fast-dissolving nanofiber mats using different concentrations of PVP (20% and 25% w/w). The characterization of the rapidly dissolving nanofiber mats encompassed aspects such as drug content, fiber diameter, morphology, disintegration time, drug release behavior, and interactions between the drug and excipients.

Results

The diameter of nanofibers increased with the increase in PVP concentration in the formulations. The dissolution rate of the PVPE-20 and PVPE-25 formulations showed a high release of antioxidants from both formulations. The results revealed that a significantly higher release of antioxidants was observed in the PVPE-25 formulation, displaying the highest initial burst release of approximately 70.9% within the first minute, and releasing the entire drug, about 87.5%, within the first 5 min. Stability tests showed that the formulations were not significantly affected by storage.

Conclusion

The preliminary results presented here as a proof-of-concept demonstration will illuminate future designs and applications of fast-dissolving mats incorporating P. latifolia leaf extract via the electrospinning method.

Graphical Abstract

Purpose

PLGA nanoparticles are one of the most investigated drug delivery systems among all polymeric nanoparticles. Although there are several successfully developed and marketed microparticulate PLGA systems, unfortunately, there was little progress in the in vitro to clinic and marketing translation of PLGA nanoparticulate systems. One of the main reasons is the very low drug-loading capacity of PLGA nanoparticles. This situation becomes more problematic in some drugs such as doxorubicin. Doxorubicin is a very interesting molecule whose solubility and characteristics dramatically change depending on pH and the presence of various ions and compounds in the medium. This property of the doxorubicin probably directly influences the drug loading of the doxorubicin to PLGA nanoparticles. In this study, it was aimed to improve the doxorubicin loading to PLGA nanoparticles while the average particle size and polydispersity index are in the acceptable ranges.

Method

TOPSIS-based Taguchi experimental design was adopted and the effect mainly water phase additive on drug loading, encapsulation efficiency, particle size, and polydispersity index were investigated.

Result

Results show that generally using PBS and HEPES improves the overall results when compared with blank water as the water phase.

Conclusion

Within the study, TOPSIS-based Taguchi design was successfully applied to the optimization of a PLGA nanoparticle formulation, and the optimum water phase additive was determined. These findings will be very beneficial to the researcher in the field of doxorubicin-loaded PLGA nanoparticles in their future studies.

Purpose

Powder feeding is a vital unit operation in the continuous manufacturing of pharmaceutical products. Loss-in-weight twin-screw feeders are commonly used in continuous manufacturing lines. The feeding performance, i.e., the accuracy and consistency of feeding, influences the content uniformity of the final drug product. In this study, a redesigned hopper for K-Tron KT20 twin-screw feeder was designed, implemented, and investigated to improve feeding performance. The basic idea was to design the hopper in such a way that the stresses on top of the screw entrance are independent of the fill level.

Methods

Our study compared the novel system to that of the original cylindrical hopper. The effect of the redesigned hopper on the start-up, the process’ sensitivity to refill level, and the refill portion size were studied. A free-flowing, barely compressible powder and a compressible blend were used in this study to evaluate the feeding performance and the refill effects.

Results

When using compressible powders, the results showed a larger process window for refilling in the redesigned hopper and a lower refill-level sensitivity compared to the original hopper.

Conclusion

The homogenization of stresses in the redesigned hopper allowed operating at lower refill levels, and variability, especially due to refilling, was reduced. This study demonstrates novel design approaches for successfully implementing hard-to-feed materials in continuous manufacturing.

Purpose

With the increasing demand for intensified processes in biopharmaceutical manufacturing, there is a growing requirement for a rapid and precise analytical method to measure product yield. Aligning with FDA guidelines, this requirement aims to enhance process monitoring and control. Currently, the monitoring of monoclonal antibody (mAb) titer during manufacturing heavily relies on offline testing conducted in quality control laboratories. However, the lengthy turnaround time for analytical results, often taking hours or even days, undermines their usefulness for process control and decision-making.

Methods

This manuscript presents a case study on HaLCon® protein analyzer, a compact Liquid Chromatography (LC) system equipped with a Protein A affinity column. HaLCon® is specifically designed for at-line/on-line titer measurement directly at the biopharmaceutical manufacturing site, enabling the rapid acquisition of product yield information. The study investigates the capabilities, performance, and potential applications of HaLCon® at the laboratory scale.

Results and Conclusion

The results obtained demonstrate the effectiveness and reliability of HaLCon® as an analytical instrument for at-line titer measurement, offering valuable insights into its potential application within the biopharmaceutical manufacturing industry.

Purpose

Oncology products often leverage accelerated approval program to seek earlier launches in the United States. Little is known about how the Food and Drug Administration (FDA) has been balancing evidence and access, and the factors that may characterize post-accelerated approval requirements. The present study aimed to obtain insights on how accelerated approval is determined by investigating the balance between pre-accelerated approval and supplemental clinical evidence required for future regular approval.

Methods

The product properties, pre-accelerated approval evidence, rationale, post-accelerated approval requirements, and prior regulatory designations for oncology accelerated approvals were summarized based on public databases. Regression analyses were performed to investigate factors that may have been associated with the post-accelerated approval requirements.

Results

Hundred fifty-seven accelerated approvals were granted between 1992 and 2021. An increase in the number of pre-accelerated approval trials by one trial resulted in a 20% decrease in supplemental trials. The endpoint for the post-accelerated approval trial tended to be more robust when products were indicated for common cancers, while less robust when products had been used to treat fewer subjects, when products were indicated for respiratory and skin cancers, or when less malignant cancers were targeted.

Conclusions

Accelerated approvals for oncology products were often based on the response rate of a noncomparative trial. However, considerable variation was observed in the post-accelerated approval requirements. Factors such as the quality and quantity of pre-accelerated approval evidence, regulatory designations, and operational feasibility may have been considered when determining the accelerated approvals and post-accelerated approval requirements.