Journal of Pharmaceutical Investigation

Despite being a leading cause of death worldwide, cancer remains difficult to treat due to the development of drug resistance and severe adverse effects associated with conventional chemotherapy. Hence, combination chemotherapy is theoretically advantageous owing to the synergistic effects of drugs and suppression of drug resistance. Nanoparticle-mediated chemotherapeutic delivery is a promising approach for the effective treatment of various cancers because it may simultaneously enhance therapeutic effects and reduce side effects. The loading of multiple chemotherapeutic agents to these systems could additionally improve the antineoplastic efficacy. This review highlights recent advances in combination chemotherapy using small-molecule chemotherapeutic agents via nanocarrier systems, e.g., liposomes, polymeric micelles, dendrimers, polymer-drug conjugates, and mesoporous silica nanoparticles. Specifically, it emphasizes the unique properties of these systems that make them amenable to optimized treatments with respect to efficacy and safety and clarifies areas in which current therapeutic strategies can be improved.

The aim of this study was to scrutinize the physicochemical and qualitative microbial examination of 30 different (of various dosage forms) herbal medicinal products marketed by pharmaceutical and herbal manufacturers in Bangladesh. The microbial evaluation included total viable aerobic bacteria, Escherichia coli, fungi and Staphylococcus aureus count; physicochemical properties like weight variation, hardness, disintegration time, friability and density. The IMViC (indole, methyl red, Voges–Proskauer and citrate utilization) tests were frequently employed for identification of E. coli and S. aureus. Total viable aerobic bacterial counts in the samples analyzed were ranged from 3.8 × 104 to 3.2 × 108 CFU/ml or CFU/g and 36.67 % were within BP standard limit. S. aureus was detected in 53.33 % (16) of the samples, ranged from an estimated 3 × 102 to 9.2 × 106 CFU/ml or CFU/g which were above the USP standard. E. coli was detected in 40 % (12) of the samples, ranging from 1 × 102 to 4.8 × 104 CFU/ml or CFU/g that were above the USP standard. The ranges of the fungi counts were 3.4 × 103–3.1 × 106 CFU/ml or CFU/g and 46.67 % of which were within BP standard. Physicochemical properties of herbal products manufactured by pharmaceutical manufacturers were found better than that of the herbal manufacturers. From the label and pack insert of herbal products, definite release pattern information weren’t obtained and the majority of herbal products showed scattered disintegration time. In order to reduce the potential health related complications, there is necessity of constant monitoring and control of the standards of herbal medicine products available in the Bangladeshi market.

Tissue distribution and observable-adverse-effect-level of cadmium selenide/cadmium sulfide (CdSe/CdS) quantum dots (QDs) were investigated to get important information of this QDs. Female BALB/c mice were treated with single intravenous (IV) injection of polyethylene glycol-folic acid-coated QDs (CdSe/CdS-PEG-FA) at different concentrations (0, 270, and 540 pmol/20 g of mice body weight), and the subsequent toxicological effect-levels were examined for 24 h. The health and apparent behaviors of the animals were normal throughout the study. The distribution of the QDs was observed in the spleen, liver, lung and kidneys, but not in the brain and heart tissues. The spleen and liver possess the highest amount of the QDs followed by the lung while the kidneys possess the few. There were no changes in the organ weight index, total protein concentration, LDH activity, and specific NADPH oxidase activity in any tested organ indicating no toxic effects of the QDs in our study. Additionally, histopathological examination did not show any cellular/tissue structural damages. Overall, single IV administration of CdSe/CdS-PEG-FA QDs to BALB/c mice allows immediate systematic availability, and showed different tissue distribution without any obvious toxic effects at our experimental design.

The main objective of the present study was to simultaneously improve the dissolution profile and content uniformity of ezetimibe (EZ), a low dose poorly soluble drug, through co-inclusion in urea. EZ, a new category of cholesterol absorption inhibitor used in the treatment of primary hypercholesterolemia and sitosterolemia, reveals extremely poor solubility in water and dissolution rate limited absorption resulting in its low bioavailability. In the current study, EZ—a highly substituted potent compound which is normally non-complexing guest (NNCG) was successfully incorporated in urea lattice in the presence of readily complexing guest (RCG). The modified Zimmerschied calorimetric method was used for the estimation of the minimum amount of RCG required per unit weight of drug for co-inclusion in urea. Ezetimibe urea co-inclusion complexes (EZUCIC) containing varying proportions of RCG and NNCG were prepared and subjected to thermal analysis using DSC. The formation of EZUCIC was confirmed by FTIR, DSC, XRD and 1H-NMR studies. The thermal data was subjected to the regression studies to study the effect of the relative molar fraction of RCG on the heat of decomposition of EZUCIC. Study exhibited improved content uniformity of EZ in EZUCIC. In vitro dissolution rate studies exhibited steep improvement in the dissolution profile of EZ, a BCS class II drug. The dissolution data was subjected to various release kinetic models. Steep improvement in the dissolution profile offer urea co-inclusion technique a promising alternative for formulation of poorly soluble potent drug candidates into immediate release products with improved content uniformity.

Staphylococcus epidermidis is one of the most common causative pathogens of nosocomial-related infections. It is known to form biofilms on indwelling medical devices. The negatively charged extracellular matrix of the biofilm can entrap bacteria, thus limiting the diffusion of therapeutic agents and contributing to the ineffectiveness of therapeutic agents against the bacteria. To combat this, we investigated the effectiveness of a cationic peptide, K16ApoE, with bioadhesive properties to serve as an anti-adhesion agent. The ability of K16ApoE to serve as an anti-adhesive agent was evaluated using crystal violet staining to quantify the degree of inhibition of biofilm formation. The minimum inhibitory concentration was determined by concurrently incubating the S. epidermidis inoculum with K16ApoE (0–250 µg/mL) for 24 h, after which a relative biofilm density assay was performed. Inhibition of the surface adhesion of biofilms to various matrices was also evaluated by coating K16ApoE on ceramic discs as well as polyvinyl chloride (PVC) or silicone catheter extension tubing. Bovine serum albumin (BSA), pure unconjugated ApoE or K16 peptide were used as controls. K16ApoE (250 µg/mL) was very effective at reducing biofilm integrity by 99.92%. ApoE or K16 alone was largely ineffective compared to K16ApoE. In addition, catheter tubing pretreated with K16ApoE showed a significant (83 ± 12.7%) reduction in the formation of adherent biofilms. These results demonstrate that K16ApoE can serve as an effective anti-adhesive agent to prevent the formation of an adherent bacterial biofilm on matrices with different surface properties.

In this study, solid dispersion for carvedilol was prepared by using spray-drying method. Solid dispersions were formulated with carvedilol and Eudragit RS and hydroxypropyl methylcellulose to control the dissolution rates of carvedilol. Scanning electron microscope was used to analyze surface of solid dispersion samples. Differential scanning calorimetry and powder X-ray diffraction were used to analyze the crystallinity of solid dispersions. Fourier transform infrared spectroscopy was used to analyze the change in chemical structure of solid dispersions. The release behavior of solid dispersion analyzed at simulated gastric fluid (pH 1.2) in in vitro study. The dissolution rate of carvedilol was higher than active pharmaceutical ingredient. In conclusion, we can control the dissolution rate by solid dispersion using biomedical polymers.

The long-term controlled delivery of drugs has been successfully achieved by biodegradable polymeric particulate systems. The drug release testing method is important for the characterization of dosage form performance under in vitro standardized conditions and can provide insight into the in vivo performance of the drug product. In vitro drug release testing methods for polymeric particulate systems are classified into sample and separate (SS), dialysis, and continuous flow (CF) methods. In the SS method, the drug-loaded microparticles are suspended in a vessel and the samples for the analysis are obtained by separating the particles using filtration or centrifugation. The dialysis method physically separates microparticles from the release media by a membrane, which eliminates the undesired loss of particles during sample preparation and handling. The CF method uses apparatus consisted of flow-through cell that holds the sample, pump and water bath in closed or open ends system. In this method, the release media is continuously circulated through a cell containing drug-loaded microparticles. This review summarizes the principles of the drug release testing methods and discusses their characteristics with the recent research results.

Acid neutralizing capacity (ANC) of antacids is an important indicator of the efficacy of such products. The purpose of this study is to evaluate the effect of pharmaceutical properties on the ANC of antacid oral suspensions. Fifteen antacid oral suspensions randomly sourced from different manufacturers and coded A1-A15 were assessed using ANC, raft formation, sedimentation profiles, ease of re-dispersibility, density, alkalinity, particle size, viscosity and rheological patterns. The effects of the pharmaceutical properties were discussed on the ANC and conclusions drawn. The results showed that ten (66.67 %) of the samples passed the ANC test among which 5 (83.33 %) were non-sedimenting highly viscous suspensions. One sample (A5) presented raft formation. Sedimentation volume reduces with time, ease of re-dispersibility was in seconds and the density range for all samples was 1.06–1.26 g/mL. The particle sizes of the antacid oral suspensions were within the range for coarse dispersions. The viscosity values ranged from 39.33 ± 1.53 to 2508 ± 24.33 cp. The rheogram of A3 shows a Newtonian flow with a regression coefficient of 0.999 and it had the least ANC. Other samples present non-Newtonian flow in a pseudoplastic pattern. Comparison of the viscosity of samples with ANC shows no direct relationship between the two variables although most samples with low viscosity failed the ANC test. The acid neutralizing capacity of the antacid oral suspensions is influenced by the dynamics of different parameters including type of active pharmaceutical ingredient, sedimentation profile, viscosity and overall rheology of the suspension.

Microemulsion-based hydrogels (MBHs) containing voriconazole were prepared as a possible topical delivery system for enhancing drug absorption at the site of action, as well as reducing the frequency of systemic side effects. Microemulsions were prepared with N-methyl-2-pyrrolidone as a surfactant, benzyl alcohol as an oil, and an ethanol/phosphatidylcholine mixture (3:2, w/w) as a cosurfactant. MBHs were prepared by adding carbopol 940 or xanthan gum as a gelling agent. In vitro skin permeation and deposition studies were performed using static vertical diffusion Franz cells and hairless mouse skin. The in vitro permeation data showed that the optimized microemulsion formulations consisting of voriconazole (1 %, w/w) and benzyl alcohol (10 %, w/w) showed significantly higher drug permeation rates and skin deposition compared to propylene glycol (control). However, the addition of a gelling agent did not significantly change the permeation profiles compared to the microemulsions. In vivo skin deposition studies conducted on hairless mice with MBHs also confirmed the superiority of MBHs compared to the control. These results suggested the MBH system to be a promising vehicle for topical delivery of voriconazole.