Drug Development and Industrial Pharmacy最新文献

Objective: Etoricoxib (ETB) is a nonsteroidal anti-inflammatory therapeutic agent. It is poorly soluble and has various gastrointestinal side effects such as bleeding and ulcers after oral administration. The present research aimed to develop an ETB-loaded mesoporous silica nanoparticle-laden gel (ETB-MSNPs) for transdermal delivery to improve therapeutic efficacy.

Methods: The ETB-MSNPs were synthesized using a precipitation and solvent evaporation technique and their optimization was performed using a Box-Behnken design. The optimized ETB-MSNPs were incorporated into a carbopol-chitosan gel and evaluated for in-vitro, ex-vivo, and in-vivo anti-inflammatory activity.

Results: The ETB-MSNPs displayed nanosize of particles with nanosize distribution and high entrapment efficiency of ETB. The FTIR and DSC studies showed that ETB was encapsulated in MSNPs. The optimized ETB-MSNPs were successfully integrated into the carbopol and chitosan gel, which exhibited excellent viscosity and spreadability. The optimized ETB-MSNPs gel exhibited a significantly higher and more sustained release of ETB compared to pure ETB gel. Optimized ETB-MSNPs gel exhibited a considerably higher anti-inflammatory effect with a significant reduction in IL-1β and TNF-α levels compared to pure ETB gel. The histopathological examination confirmed that optimized ETB-MSNPs gel did not exhibit any toxicity on the skin.

Conclusions: Based on the findings, the results suggest that the MSNPs gel has the potential as a carrier for enhancing the therapeutic efficacy of ETB through topical delivery, although further studies are needed to fully confirm its effectiveness.

Objective: To establish a detailed step-by-step example for the topical development of generic products.

Significance: Topical semisolids are complex products requiring extensive research for bioequivalence by establishing Q1/Q2/Q3.

Methods: The detailed process establishes Q1/Q2 selection and Q3 evaluation of the innovator and proposed formulation. The proposed generic product along with the innovator formulation has been evaluated for physicochemical properties. Once the Q3 structure is matched with innovator formulation, the invitro release and in-vitro permeation study have been conducted to move forward for the bioequivalence study. Pharmacokinetic and pharmacodynamic studies were employed for bioequivalence with an innovator in humans.

Results: Selection of Q1 and Q2 establish the formulation composition through literature search and reverse engineering. The test and reference products are pharmaceutically equivalent through Q3 characterization, IVRT, and IVPT. In the PK study, test and reference samples were compared for Cmax, T_max, and t_1/2 and found bioequivalent. The PD study was performed in pilot and pivotal study to establish dose duration response relationship and bioequivalence respectively without adverse events. A crucial study has exhibited that reference and test formulations are bioequivalent with a 90% confidence interval and results in 84.67%-101.09%.

Conclusion: The Cutivate^® cream 0.05%, and proposed generic product Fluticasone Propionate cream 0.05% formulations are bioequivalent and have a favorable safety profile.

Objective: Flavonols have different pharmacological actions that render them highly promising therapeutic targets. However, their water solubility and bioavailability are low, which restricts their therapeutic potential. ABNPs, albumin-based nanoparticles, are potential nanocarriers that enhance flavonol solubility, stability, and targeted delivery. By utilizing ABNPs, in this work we provide a detailed overview of strategies employed to attain maximum bioavailability of poorly water-soluble flavonols. The review critically evaluates ABNP-mediated delivery's pharmacokinetic advantage, physicochemical properties, and formulation principles. We also highlight existing gaps in research, such as the need for stringent in vivo validity tests, standardized formulation procedures, and in-depth mechanistic understanding of flavonol-albumin interactions.

Significance: Despite having potential therapeutic activities, the utilization of flavonoids in the form of medication is limited. Some recent studies have shown that flavonoids exhibit low solubility, low permeability and chemical instability, thereby limiting their bioavailability and therapeutic responses.

Methods: To overcome these drawbacks, multiple novel drug delivery approaches have emerged in the pharmaceutical research.

Results: These novel approaches seem to offer a viable foundation for improving the bioavailability of the flavonoids and positioning them as viable therapeutic options. Out of all the polymers implemented in enhancing the solubility and bioavailability of the flavonoids, albumin-based nanomaterials have been the most efficacious one.

Conclusion: Compared to all other polymeric nano-carriers, albumin nano-carriers offer a greater scale of drug entrapment and drug loading because of their capacity for surface modification, crosslinking, conjugation, coupling, and characteristics including biodegradability and biocompatibility.

Objective: This study investigates a hybrid drug delivery system combination of 5-Fluorouracil (5-FU) and Carvedilol (CVD) for enhanced chemotherapeutic efficacy in skin cancer treatment. The approach addresses challenges such as drug resistance and suboptimal delivery in conventional therapies.

Methods: Transethosomes (TEs) were developed using the Modified Ethanol Injection method, with optimization based on the concentrations of Lipoid S100, Tween 80, Polyvinyl Alcohol, and ethanol via the Box-Behnken Design. Characterization techniques, including FT-IR, DSC, Raman spectroscopy, XRD, FESEM, TEM, and AFM, were utilized to evaluate the formulations. In vitro anticancer studies, including IC50 determination, MTT assays, and cell cycle analysis, were conducted alongside drug permeation and hemolysis evaluations performed in vitro and ex vivo.

Results: The optimized transethosome formulation demonstrated a particle size of 113 nm, a zeta potential of 27.23 mV, and encapsulation efficiencies of 97.21% for 5-FU and 98.73% for CVD. Spectroscopic analyses indicated no significant drug-excipient interactions, while XRD confirmed the amorphous nature of the drug in the formulation. Microscopy revealed spherical vesicles with uniform coating. The formulation showed significant anticancer activity in in vitro studies.

Conclusion: The combination of 5-FU and CVD within a transethosome-based delivery system presents a potential alternative for topical chemotherapy in skin cancer treatment, offering enhanced therapeutic efficacy. This study underscores the potential of hybrid drug carriers in advancing targeted cancer therapies.

Objective: The study aimed to formulate and optimize Lapatinib-loaded calcium pectinate nanoparticles (LAP-PEC-NPs) using central composite design (CCD), evaluate their physicochemical properties, and compare their anticancer efficacy with raw LAP on MCF7 breast cancer cell lines.

Significance of review: The study is significant as it successfully developed LAP-PEC-NPs through systematic optimization. These nanoparticles exhibited favorable physicochemical properties, high drug entrapment, and sustained release. The effective inhibition of MCF7 breast cancer cell growth by LAP-PEC-NPs underscores their potential as a promising cancer treatment strategy, enhancing LAP's therapeutic efficacy and bioavailability.

Key findings: LAP-PEC-NPs were successfully developed using an ionic gelation process. The optimization resulted in an ideal formulation with a polydispersity index (PDI) of 0.289, a droplet size of 93.65 nm, and a zeta potential of -17.32 mV. LAP's amorphous nature within the nanoparticles' porous matrix was confirmed through characterization techniques. Dissolution studies showed sustained drug release, with LAP-PEC-NPs releasing approximately 75% of LAP over 72 h, significantly higher than raw LAP. Evaluation of MCF7 breast cancer cell lines revealed that LAP-PEC-NPs effectively inhibited cell growth.

Conclusions: The study successfully developed and optimized LAP-PEC-NPs, yielding nanoparticles with desirable characteristics. The sustained drug release kinetics and promising anticancer efficacy of LAP-PEC-NPs suggest their potential as a therapeutic strategy for breast cancer treatment. These findings pave the way for further preclinical and clinical studies to validate the efficacy and safety of LAP-PEC-NPs for clinical translation.

ObjectiveNanomedicine is the application of nanotechnology to medicine and, therefore, a potentially transformative approach to healthcare. This new and interdisciplinary field has three main applications in diagnostics, controlled/targeted drug delivery, and regenerative medicine. Nanomedicine has a great potential to change human health by advancing diagnosis, prevention and treatment for a wide variety of diseases, including cancer, cardiovascular conditions, and neurological disorders. Despite overwhelming potential, there are some issues impeding the complete integration of nanomedicines into healthcare systems.SignificanceThis policy brief addresses such critical issues to inform and guide decision-making on effectively deploying nanomedicine to improve patient outcomes and advance important public health initiatives. In addition, some prospects were also presented for future.Key findingsThese brand-new nanosystems have some serious drawbacks in regard to safety, efficacy, and regulatory compliance, not to mention public acceptance. Nanomaterials can be so complex that their manufacturing processes become complex, which may potentially bring into question long-term effects on human health and the environment. It discusses the current barriers to their wide application, particularly regarding regulatory hurdles and the production of robust clinical evidence.ConclusionsThis policy brief identifies key considerations for policymakers and stakeholders, highlighting the requirement for integration among researchers, clinicians, and regulatory bodies. To facilitate safe and successful integration of nanomedicines into patient care, continued collaboration are imperative. Priority in the future should be given to developing comprehensive regulatory frameworks, raising public awareness, and promoting interdisciplinary research to resolve existing challenges and unlock the potential of nanomedicines in the healthcare sector.

Purpose: Cyclophosphamide, an active pharmaceutical ingredient (API), is accessible in monohydrate form and esteemed for its remarkable stability. Maintaining this monohydrate form post-lyophilization is essential for product stability. This research aims to optimize essential lyophilization parameters for an effective and robust lyophilization cycle using a Quality by Design (QbD) methodology.

Methods: Initially, thermal analysis is performed to evaluate the thermal qualities of the product. The research defines critical process parameters (CPPs) and important quality attributes (CQAs), employing a systematic Quality by Design (QbD) methodology to establish the design space in accordance with the required Quality Target Product Profile (QTPP). The lyophilization parameters being examined are primary drying temperature, primary drying duration, and primary drying vacuum. Meticulous analysis of the results identifies an optimum formulation.

Results: The test product successfully preserves water content between 6 and 7%, hence confirming the existence of the monohydrate form, as verified by X-ray diffraction (XRD) examination. Furthermore, the product demonstrates minimal concentrations of TBA and ACN, maintains an intact cake structure, and achieves a rapid reconstitution time of less than 30 s.

Conclusion: The implementation of Quality by Design (QbD) concepts to enhance lyophilization parameters offers significant insights for developing generic pharmaceutical lyophilization formulations. Ultimately, a reliable freeze-drying technique is developed and then requires validation on industrial-scale lyophilizers for commercial applications.

Aim: This study focuses on the formulation and evaluation of Tacrolimus-loaded transethosomes, which are then incorporated into a gel for topical application. The goal is to achieve deeper transdermal penetration, enhancing the treatment regimen.

Methods: Transethosomes were formulated using the cold method and optimized using 3² factorial design (DESIGN EXPERT^® Software) using different concentrations of lipid and ethanol. They were characterized for vesicle size, entrapment efficiency, zeta potential, and polydispersity index. The optimized batch was incorporated into the carbopol 940 gel base. In vitro and ex vivo permeation studies were carried out to determine the diffusion and release pattern. Skin irritancy and in vivo imiquimoid-induced anti-psoriatic activity were carried out on Wistar rats.

Results: The F1 batch, characterized by a low concentration of ethanol and lipids, demonstrated a vesicle size of 168 nm, an entrapment efficiency of 85%, a zeta potential of -36 mV, and a polydispersity index of 0.12. In vitro release studies indicated an 85.32% drug release and a 76.34% drug permeation after 24 h. The drug release adhered to zero-order kinetics, with the Korsmeyer-Peppas model suggesting a non-Fickian diffusion mechanism. In vivo studies of Tacrolimus-loaded transethosomal gel in an imiquimod-induced psoriasis-like rat model demonstrated significant therapeutic effects within seven days. Histopathological analysis showed reduced hyperkeratosis, epidermal hyperplasia, and inflammation, with fewer inflammatory cells in the dermis. Stability tests confirmed the formulation's integrity at 4 and 25 °C over 90 days.

Conclusion: The study's outcome revealed that tacrolimus-loaded transethosomes could effectively manage psoriasis.

Objective: This review aims to explore innovative therapeutic strategies, with a particular focus on recent advancements in drug delivery systems using bioinspired nanomaterials such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the idiopathic pulmonary fibrosis (IPF).

Significance of the review: Current treatments for IPF, including the FDA-approved anti-fibrotic agents pirfenidone and nintedanib, primarily aim to slow disease progression rather than reverse fibrosis. Bioinspired nanomaterials like SLNs and NLCs have shown promise in enhancing the efficacy of anti-fibrotic agents by improving drug solubility, stability, and targeted delivery. These systems not only minimize systemic side effects but also maximize therapeutic impact in lung tissues, offering a new hope for improved patient management and outcomes in this debilitating disease.

Key findings: SLNs facilitate sustained drug release and have demonstrated potential in delivering phosphodiesterase type 5 inhibitors effectively to lung cells. NLCs, on the other hand, exhibit superior biocompatibility and controlled release properties, making them suitable for pulmonary applications. Studies indicate that both SLNs and NLCs can enhance the bioavailability of drugs like ciprofloxacin and montelukast, thereby improving treatment outcomes in pulmonary conditions.

Conclusion: The integration of nanotechnology into anti-fibrotic therapy represents a significant advancement in addressing the challenges posed by IPF. By leveraging the unique properties of SLNs and NLCs, there is potential to overcome the limitations of current treatments and provide new therapeutic options that offer better management and improved outcomes for patients suffering from this debilitating disease.