Journal of pharmaceutical sciences最新文献

This study reveals specific ion effects on particle formation during peristaltic pumping of a monoclonal Antibody (Antibody A). For this purpose, three anions in the direct Hofmeister series were selected, ranging from the kosmotropic SO₄^2- to the more neutral Cl^- and the chaotropic SCN^-. Protein particle formation during peristaltic pumping is described primarily as a surface-driven mechanism. Therefore, the effect of the anions was hypothesised to affect the particle formation with the smallest amount of protein adsorbing and the least particles formed in the presence of SCN^-, followed by the highest in SO₄^2-. The alternative hypothesis was that most protein particles would be formed in SCN^- due to the lower intrinsic stability of Antibody A. On the other hand, if none of the factors dominates the particle formation, it would not necessarily follow the Hofmeister series linearly. This was shown to be the case as significantly more particles were formed in the presence of NaCl, which could be explained by the interplay of the protein's intrinsic, colloidal, and interfacial stability. Antibody A had the highest protein adsorption in NaCl and the lowest colloidal stability compared to Na₂SO₄ or NaSCN, which led to the highest amount of subvisual particles formed during pumping.

The present study reports the preparation of sodium alginate-cetyltrimethylammonium bromide (CTAB) nanoparticles (SANPs) through the interaction of a fixed concentration of alginate (0.2% w/v in water) with two different concentrations of CTAB i.e., below (0.4 mM) and above (1.2 mM) critical micelle concentration (CMC) and the elucidation of its structure on the basis of dynamic light scattering, transmission electron microscopy, small angle neutron scattering and zeta potential measurements. The results indicated that the concentration of CTAB dictated the hydrodynamic shape and size of SANPs. While both the micellized (> CMC) and monomeric forms (< CMC) of CTAB resulted in the formation of negatively charged near spherical particles, the SANPs containing micellized form of CTAB exhibited smaller and more compact hydrodynamic structure compared to those containing monomeric form of CTAB. The cytotoxicity studies involving cancerous cell lines (A549 and L132) indicated that the anticancer activity of CTAB was retained in the SANPs. Subsequently, encapsulation of doxorubicin (DOX), a potent anticancer drug in to SANPs enhanced the efficacy of the overall nano-formulation for effectively killing A549 and L132 cells. Additionally, the DOX loaded SANPs also exhibited the sustained and pH dependent drug release under reservoir-sink model. Together, polyelectrolyte complexation between alginate and CTAB appears as a novel strategy to design nano formulation exhibiting anticancer activity perse as well as for sensitizing the efficacy of chemotherapeutic drugs.

Nanocellulose, a sub-micron cellulose powder, was investigated as a potential filler excipient to enhance the tabletability of acetaminophen (APAP). Due to its high specific surface area, nanocellulose was expected to outperform the tabletability enhancement provided by microcrystalline cellulose (MCC), a common tablet filler used in pharmaceutical tablets. Results showed that nanocellulose is inferior to MCC when used as a conventional filler. This is due to the difficulty in deaggregating and dispersing aggregates of nanocellulose using a typical dry blending process. To improve its effectiveness, nanocellulose prepared as a suspension was blended or "co-processed" with APAP using a twin-screw process. Microscopy images show that the twin-screw process coats the APAP with nanocellulose. The tabletability of APAP was significantly improved by low concentrations of nanocellulose up to 1.10% w/w. Such remarkable improvement allowed acetaminophen to be processed into tablets without any additional excipients. This study shows that nanocellulose can be used as a highly functional additive to enhance tabletability at low concentrations.

Atorvastatin calcium is an antihyperlipidemic with low bioavailability, and to address this limitation, a transdermal delivery system utilizing transethosomes as a carrier was developed. This study aimed to enhance the bioavailability of atorvastatin calcium by transitioning from oral to transdermal administration. The six different formulas of transethosomes were observed based on particle size, PDI, zeta potential, deformability index, and morphology. Furthermore, the patch's characteristics, penetration, pharmacokinetic, and irritation studies of transethosomes patch were observed. The results showed that atorvastatin calcium transethosomes had a particle size of ≤ 130.59 nm with PDI and zeta potential values of ≤ 0.24 and ≥ -51.87 mV, respectively. The vesicles featured spherical morphology and an excellent deformability index. The transethosome patches obtained had a pH and viscosity value of 5.7 and ≥ 8741 m.Pas, respectively. The properties of transethosomes loaded in the patch were observed to show a particle size of ≤ 249.83 nm and zeta potential ≥ -44.73 mV. A penetration study of the atorvastatin calcium transethosomes patch reveals high flux, especially the G6 formula, increasing bioavailability by 3.67-fold and not irritating. In conclusion, developing a transethosomes patch for transdermal delivery proved to be an effective method for enhancing the bioavailability of atorvastatin calcium.

The recently proposed Polli equation [Polli JE. A simple one-parameter percent dissolved versus time dissolution equation that accommodates sink and non-sink conditions via drug solubility and dissolution volume. AAPS J 2023;25:1] has been discussed in the context of its ability to fit experimental dissolution transients obtained under either sink or non-sink conditions. In this work, we reveal that the Polli equation describes a complex dissolution mechanism that combines classical first-order (Noyes-Whitney, N-W) kinetics with a second-order mechanism. Possible origins of the second-order process are discussed within the framework of small-molecule drug dissolution, after first probing the general utility of the higher-order rate term in more precisely fitting typical dissolution transients (for ibuprofen and ketoconazole) taken from the referenced work. Lastly, molecular dynamics (MD) simulations are performed using the prototypical drug, bupivacaine, that is shown to dimerize in aqueous solution under acidic conditions. Our findings point us to conclude that the Polli mechanism best describes cases where the drug forms dimers in solution at a rate comparable to that with which it dissolves (per the N-W mechanism), given non-sink conditions. Under sink conditions, the Polli mechanism is first-order in drug concentration.

The quality attributes of topical foams are critical in determining the rate and extent of drug absorption across the skin and mucous membranes. A generic product is required to match the reference-listed drug (RLD), with respect to its composition and characteristics. Time to break (TB) is one of the critical quality attributes to consider during the evaluation of some of the generic products, as per the product-specific guidance from the Food and Drug Administration (FDA). This paper proposes a slightly modified protocol for conducting TB studies to improve the robustness of the test and reduce the ambiguity in its assessment. The proposed modified method "Time to Break and Evaporation (TBE)" is a gravimetric method that considers the collapse and loss of solvents and other volatile components from the foam. A marketed salicylic acid foam product was used as a model to demonstrate the practicality of this modified approach.

Abraham solvation equation (Absolv) is a popular and well-established approach for modeling solute partitioning between phases of different polarity, which finds its applications in both organic chemistry and biomedical fields. Parameters constituting this equation are good quantitative descriptors of solute hydrogen bonding potential that are useful for QSAR modeling of more complex chemical and biological phenomena. Numerous studies dealing with fast determination of Abraham descriptors using HPLC can be found in the literature, but these mostly focus on small un-ionizable industrial and environmental chemicals, whereas experimental data for pharmaceutical molecules are clearly lacking. In the current study we build upon a previously published chromatographic approach, aiming to adapt the method to ionizable drug-like compounds, and optimize it by reducing the number of required HPLC columns. The analysis involves determination of the overall H-bond acidity (A), H-bond basicity (B) and polarity/polarizability (S) descriptors for 62 pharmaceutical molecules with previously unpublished parameter values.

This study aims to develop an innovative multifunctional and dual responsive drug formulation for precise siRNA delivery to breast cancer sites, addressing the challenges posed by conventional cancer treatments which often result in adverse side effects due to their non-specific nature. The formulation made by incorporating gold coated superparamagnetic iron oxide nanoparticles (Au-SPIONs) into chitosan microspheres, which were subsequently loaded with siRNA. Comprehensive characterization, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and energy-dispersive X-ray spectroscopy (EDS) confirmed the formulation's favourable morphology, particle size distribution, chemical composition, and stability, indicating its strong potential for effective siRNA drug delivery applications. The developed formulation demonstrated siRNA encapsulation efficiencies ranging from 27.4 % to 88.6 % and loading capacity from 0.291 % to 1.59 %, these values particularly higher for medium molecular weight chitosan. These results were compared across different formulations, showing that variations in chitosan type and crosslinker concentration significantly influenced encapsulation efficiency and drug release profiles. Additionally, our results were compared to previous studies on chitosan microspheres encapsulating organic drugs and siRNA, where the developed system demonstrated similar encapsulation and release properties.. The type of chitosan and the choice of crosslinker significantly influenced the drug release patterns. Diverse release profiles across batches highlighted the necessity for precise formulation control. Incorporating SPIONs into chitosan microspheres presents a promising strategy for magnetically driven, site-specific drug delivery. The dual pH-responsive and magnetic properties enable rapid and targeted siRNA release, leveraging the acidic tumor microenvironment as an internal stimulus in addition to external magnetic stimuli. This novel combination of SPIONs, chitosan microspheres, and siRNA encapsulation represents a new approach for targeted drug delivery. While further research is needed to refine and optimize this approach, our study provides a proof of concept for advancing targeted cancer therapies.

This work describes the first development of high-concentration suspension formulations of human immune globulin. Colloidal-level dispersions of immune globulin were achieved by suspending a spray dried solid powder of protein in a protein solution made saturated by the addition of pharmaceutical excipients. The spray drying process was used to generate ∼90 % of particles below 20μ. The monomer and aggregates content of immunoglobulin were found to be 93 % and 0.3 %, respectively. The injection forces for the colloidal suspensions were characterized using a dynamic compression test. The concentrations of 300, 380, and 400 mg/mL formulations were injected at 3.8 N, 10 N, and 16.5 N of maximum injection forces, respectively, when a 24-gauge needle was used. The viscosity of a 300 mg/mL suspension was 128 cP. The viscosity of a 380 mg/mL suspension was 284 cP, and the viscosity was higher for the 400 mg/mL formulation; however, injectability was not an issue, which remains rare for non-Newtonian, shear-thickening systems. It is acknowledged that the 400 mg/mL suspension formulation remained relatively challenging as compared to other suspensions for injection because of its very high viscosity, and significant force was required to inject it. We show that where ultra-high-concentration immune globulin is being developed within reasonable constraints of pharmaceutical regulation, with an injectability parameter, formulations might make their way to the clinic when viscosity could say otherwise. However, further work should be conducted to assess chemical stability (using methods such as mass spectrometry) along with forced degradation studies prior any clinical use.