Drug Development and Industrial Pharmacy最新文献

Introduction: Formulation research benefits from high-throughput excipient screening methods, considering the ever-growing excipient space. We investigate the use of 384-well plates as freeze-drying containers and for subsequent analyses, to screen the effect of excipients on the stability of proteins during freeze-drying.

Methods: For both the preparation and analysis methods of a range of β-galactosidase formulations, an 8-tip pipetting robot was used. Formulations were lyophilized in 384-well plates, which were also used for subsequent enzymatic activity assessment, serving as an indication of protein stability.

Results: Excipient screening revealed that threonine, histidine, arginine, sucrose, and trehalose enhance the recovery of the enzymatic activity of β-galactosidase compared to the protein freeze-dried in buffer without other excipients. Moreover, pullulan only showed a stabilizing effect when it was combined with low-molecular-weight excipients that by themselves were poor stabilizers, which was especially the case for serine and to some extent for valine.

Discussion: There were no significant differences in enzymatic activity when comparing the automated 384-well plate freeze-drying method with a common in-vial method, while offering the added sustainability benefits of increased throughput, reduced workload, and lower protein and reagent usage. This approach might be suitable for the pre-selection of viable formulations.

Objective: This study aimed to develop and evaluate ginsenoside Rg3 (GRg3)-loaded alginate/poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) as an oral drug delivery system with improved anticancer and antioxidant potential.

Significance: Despite its pharmacological promise, GRg3 suffers from poor solubility, instability, and low oral bioavailability. Encapsulation in biopolymeric NPs may overcome these barriers by enhancing stability and providing controlled release.

Methods: GRg3-loaded alginate/PLGA NPs were synthesized and characterized for size, stability, rheology, and release kinetics. Antiproliferative activity, cell cycle effects, and apoptosis markers were assessed in PC-3 prostate cancer cells. In vivo safety and antioxidant effects were evaluated in healthy rats using biochemical assays and histopathological analysis of liver and kidney tissues.

Results: The NPs had a mean diameter of ∼200 nm with shear-thinning behavior. GRg3 release followed a sustained pattern, best fitting the Korsmeyer-Peppas model with anomalous transport. In vitro, the formulation inhibited PC-3 cell proliferation in a concentration- and time-dependent manner, induced G0-G1 arrest, and elevated caspase-3 activity within 6 h. In vivo, oral administration caused no significant hepatic or renal alterations, and histopathology showed no inflammation or necrosis. GRg3 also reduced malondialdehyde levels, confirming antioxidant activity.

Conclusions: Encapsulation of GRg3 in alginate/PLGA NPs enhanced its stability, anticancer activity, and antioxidant potential without systemic toxicity. These findings highlight the promise of GRg3-loaded nanocarriers for cancer therapy, warranting further evaluation in disease-specific models.

Objective: To explore the advancements and therapeutic potential of nanocarrier-based drug delivery systems in improving drug administration, targeting efficiency, and patient outcomes, particularly in complex disease management.

Significance: Traditional drug delivery methods often suffer from limited targeting ability, poor bioavailability, and increased side effects. Nanocarriers, such as liposomes, dendrimers, polymeric nanoparticles, and solid lipid nanoparticles, offer innovative solutions by enabling site-specific delivery, controlled release, and enhanced therapeutic indices, thereby transforming pharmaceutical care.

Methods: This review examines the current literature and recent innovations in nanocarrier design and application. It highlights stimulus-responsive systems (e.g. pH- or temperature-sensitive nanocarriers) and assesses their roles in treating conditions such as cancer, rheumatoid arthritis, and neurological disorders. This study also analyzes technological trends and translational challenges in clinical applications, including regulatory and safety concerns.

Results: Recent developments in nanotechnology have enabled the creation of multifunctional, targeted, and stimuli-responsive nanocarriers capable of delivering therapeutic agents with improved precision and efficacy. These systems significantly enhance drug absorption and retention at the target site, provide sustained release, and minimize systemic side effects of the drug. Preclinical and early clinical data support their effectiveness in overcoming the limitations of conventional therapies.

Conclusions: Nanocarrier-based drug delivery systems represent a paradigm shift in therapeutic strategies, offering precision-targeted treatment with improved efficacy and safety. Despite regulatory and translational challenges, continued research and innovation are accelerating their path to clinical adoption, establishing nanocarriers as the cornerstone of personalized medicine in cancer therapy.

Objective: This review critically evaluates chromatographic methodologies for impurity profiling and stability-indicating analysis of ceftriaxone sodium, with particular focus on polymerized impurities that pose significant patient safety concerns.

Significance: Ceftriaxone sodium, a widely prescribed third-generation cephalosporin, exhibits broad-spectrum antibacterial activity and convenient once-daily dosing. However, impurities-particularly polymerized forms-pose safety risks such as hypersensitivity and anaphylaxis. In contrast to earlier review focused on drug determination, this work emphasizes impurity profiling and highlights gaps in current analytical practice.

Methods: A systematic literature survey was conducted across official pharmacopoeias and major databases (ScienceDirect, Scopus, PubMed, Google Scholar) using keywords: ceftriaxone sodium, impurity profile, polymerized impurities, ceftriaxone stability, and ceftriaxone degradation.

Results: Reversed-phase HPLC with C18 columns was the predominant technique (93%), most commonly coupled with UV detection at 254 nm. Isocratic elution was applied in 82% of methods, with acetonitrile as the preferred organic modifier; ion-pairing agents were used in 39% of cases, and 20 µL was the most commonly used injection volume (54%). Only 14% of studies addressed polymerized impurities, with the Chinese Pharmacopeia uniquely mandating gel filtration chromatography for their assessment.

Discussion: Current impurity profiling strategies have limitations in detecting polymerized forms due to their low abundance, variable polymerization degrees, poor stability, and interference from co-existing molecules.

Conclusions: There is an urgent need for robust, sensitive, and polymer-specific analytical approaches to improve impurity profiling, and safeguard patient safety. Future studies should incorporate greenness (AGREE), risk (RAPI), and analytical performance (BAGI) metrics to identify sustainable and reliable strategies for ceftriaxone impurity assessment.

Background: Integration of artificial intelligence such as machine learning into pharmaceutical sciences has become increasingly necessary since rapid progress of novel drug delivery systems and increasing demand to accelerate research while reducing time and cost. According to the controllable nature of nanoparticle characteristics, ML algorithms offer a promising approach to predict critical properties of drug delivery systems including drug release profiles.

Objective: This study aimed to develop and investigate the machine learning models for prediction of cumulative drug release profile from chitosan nanoparticles, based on different physicochemical parameters in formulation.

Methods: In this study, we extracted experimental data from 115 research articles published between 2000 and 2020 with focus on chitosan nanoparticles prepared by ionic gelation method. For prediction of cumulative drug release profiles at multiple time points, after curating 190 datapoints with appropriate physicochemical parameters, we developed and evaluated two supervised ML models including Random Forest Regression and XGBoost using R² and MSE as evaluation parameters. Additionally, to improve model performance, we used feature importance analysis to identify and remove less influential variables.

Results: The results demonstrated that Random Forest Regression consistently outperformed XGBoost at the most time points. Furthermore, some variables like release medium temperature and drug solubility were excluded in a refined models since minimum contribution in model accuracy. The refined models showed improvement in prediction performance.

Conclusion: These findings highlight the value of ML-based modeling in pharmaceutical formulation and emphasis its potential as a powerful tool for design and optimization of nanobased drug delivery systems.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by elevated pulmonary arterial pressure, causing vascular remodeling and eventual right heart failure. Sildenafil citrate (SC), a selective phosphodiesterase-5 inhibitor, used in PAH management; however, its clinical utility is limited by poor aqueous solubility and low oral bioavailability (38 - 42%).

Objective: This study aimed to develop an extended-release sildenafil citrate formulation using tartaric acid pellets as the core, with a solid dispersion system incorporating Soluplus^® and Tween^® 80 to enhance solubility and sustain release.

Method: A spray-drying technique was employed to prepare the solid dispersion, and a factorial design was used to optimize the formulation parameters. The optimized dispersion was layered onto inert tartaric acid and subsequently coated with 7% ethylcellulose and hypromellose (80:20) to achieve sustained drug release.

Results: The optimized formulation (DS03), comprising a 1:1 ratio of Soluplus^®: to SC with 10% Tween^® 80, increased SC solubility by 50% in FaSSIF (pH 6.5), from 0.04 to 0.06 mg/mL. Incorporation into coated tartaric acid pellets further enhanced solubility to 0.51 mg/mL, representing a 1,175% improvement over pure SC (a 12.75-fold increase). The formulation provided sustained drug release for up to 12 h, with a mean dissolution time (MDT) of 190 min, compared to less than 20 min for the immediate-release reference (Revatio^®).

Conclusion: This novel extended-release system significantly improves SC solubility and enables prolonged release, which may reduce dosing frequency and adverse effects, enhancing patient adherence. Further studies on stability and pharmacokinetics are warranted to support clinical application.

Objective: The penicillin G acylase (PGA) enzyme, found in bacteria, yeast, and fungi, is used to produce 6-aminopenicillanic acid (6-APA) and beta-lactam antibiotics. To improve the catalytic activity and reusability of PGA, an efficient immobilization protocol was recruited.

Methods: In this research, Fe₃O₄ magnetic nanoparticles (Fe₃O₄ MNPs) were functionalized through polyethylene imine, and the PGA was immobilized on nanoparticles using a glutaraldehyde linker. The nanoparticles were monodispersed with spherical shape and size of around 35 nm and analyzed by SEM and DLS methods. The optimization process was performed by Design Expert 10.0 software based on the RSM method and CCD design. The immobilization of the enzyme was confirmed by FT-IR.

Results: At optimal stabilization conditions, the maximum amount of 6-APA intermediate substance was obtained at a temperature of 10 °C and a time of 336 min. The V_max and K_m were obtained around 0.024 and 1.04 mM for free PGA, and 0.47 and 1.53 mM for immobilized PGA. The stabilization increased the maximum speed of penicillin hydrolysis by a 2-fold. The antibiotic ampicillin was synthesized using 6-APA and phenylglycine methyl ester (PGME), and the immobilized enzyme maintained 45.87% of the initial activity after 10 reuse cycles, indicating that the immobilized enzyme had good stability and reusability.

Conclusions: Overall, our results showed that this nanoparticle could be considered a promising matrix for PGA immobilization, with the advantages of high catalytic efficiency and enhanced stability and reusability.

Objective: This review aims to evaluate the therapeutic potential of Risperidone (RSP)-loaded nanoparticles as an innovative drug delivery approach for effective schizophrenia (SZ) management and improved patient outcomes.

Significance: Schizophrenia is a long-standing mental disorder involving disturbances in thought, perception, and behavior, frequently necessitating extended pharmacologic therapy. While RSP, a second-generation antipsychotic, is efficacious against both positive and negative symptoms, its therapeutic use is impaired by limited water solubility, low oral bioavailability, extensive first-pass metabolism, and dose-dependent side effects. Overcoming these limitations may substantially benefit patient outcomes. Recent advances in nanotechnology have allowed the development of several RSP-loaded nanocarriers such as polymeric nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers.

Key findings: This review evaluates these systems according to drug loading efficiency, release kinetics, brain-targeting capacity, and drug administration routes, according to preclinical data. RSP nanoparticles exhibited improved solubility, sustained release, enhanced brain targeting, and decreased systemic toxicity. Intranasal and parenteral routes are additional advantages in enhancing bioavailability and compliance in non-compliant patients. Such formulations provide improved pharmacokinetic profiles and reduce extrapyramidal symptoms.

Conclusion: RSP-loaded nanoparticles are a valuable innovation in SZ therapy through enhancing efficacy, minimizing side effects, and improving patient compliance. More clinical studies are warranted to determine their safety, long-term efficacy, and commercial viability for translation into the clinic.