Current Issue : October-December Volume : 2024 Issue Number : 4 Articles : 5 Articles
Background: The threat of antibiotic resistance of fungal pathogens and the high toxicity of the most effective drugs, polyene macrolides, force us to look for new ways to develop innovative antifungal formulations. Objective: The aim of this study was to determine how the sterol, phospholipid, and flavonoid composition of liposomal forms of polyene antibiotics, and in particular, amphotericin B (AmB), affects their ability to increase the permeability of lipid bilayers that mimic the membranes of mammalian and fungal cells. Methods: To monitor the membrane permeability induced by various polyene-based lipid formulations, a calcein leakage assay and the electrophysiological technique based on planar lipid bilayers were used. Key results: The replacement of cholesterol with its biosynthetic precursor, 7-dehydrocholesterol, led to a decrease in the ability of AmB-loaded liposomes to permeabilize lipid bilayers mimicking mammalian cell membranes. The inclusion of plant flavonoid phloretin in AmB-loaded liposomes increased the ability of the formulation to disengage a fluorescent marker from lipid vesicles mimicking the membranes of target fungi. I–V characteristics of the fungal-like lipid bilayers treated with the AmB phytosomes were symmetric, demonstrating the functioning of double-length AmB pores and assuming a decrease in the antibiotic threshold concentration. Conclusions and Perspectives: The therapeutic window of polyene lipid formulations might be expanded by varying their sterol composition. Polyene-loaded phytosomes might be considered as the prototypes for innovative lipid antibiotic formulations....
Liquid-filled hard gelatin capsules may have pertinent advantages both for therapeutic effect and extemporaneous preparations of medicines. Alpha lipoic acid is a substance used in medicines and dietary supplements and there is a need for creating an appropriate formulation which would be suitable for each individual patient or consumer. Based on its biopharmaceutical and physical chemical characteristics, eight different capsule formulations were designed and characterized. Silicon dioxide was added to form a semisolid content and prevent leakage. The formulation filled with alpha lipoic acid solution in polyethylene glycol 400 showed the best performance. Although the addition of silicon dioxide to the formulation with polyethylene glycol 400 led to a change in both flow character and viscosity, the release rate did not show a statistically significant decrease (more than 85% of content was released after 5 min testing). Applied technique is a simple and an appropriate approach for compounding and could be used for other substances with similar properties....
Alectinib HCl (ALBHCl) is a tyrosine kinase inhibitor used for non-small cell lung carcinoma (NSCLC). The aim of this study is to unlock some of the physicochemical properties of ALBHCL that serve as a database for any future studies. A solubility study of ALBHCL was performed in different solvents. Also, photostability was tested in the solution and solid states, and the order of reaction and rate constant were calculated. In addition to the pH solubility relation, the pH-rate relation at different temperatures was also studied, and the profiles were constructed. A solubility study was also performed in different media for the purpose of optimizing suitable sink conditions for the in vitro dissolution testing of solid dosage forms. Solubility tests in multiple solvents and pH conditions revealed that the highest solubility was in DMSO, methanol, and chloroform, with acidic media yielding the maximum solubility but degrading at rather low pH levels. ALBHCL proved unstable at high temperatures and under light exposure, with varying stability across different pH levels. The optimal dissolution media for in vitro oral dosage form evaluation were determined, achieving sink conditions at pH levels of 6.8 and 4.5 with specific additives. This study enhances the existing database on ALBHCL’s physicochemical properties, emphasizing the importance of pH optimization in pharmaceutical processes and providing valuable insights into its pharmaceutical application....
Controlled-release tablets offer several benefits, such as controlled release, odor masking, ease of use, stability, extended shelf life, and reduced production costs. This study developed combined curcumin controlled-release tablets (CCCTs) to increase the bioavailability of curcumin with hydroxypropyl methylcellulose (HPMC), chitosan, and sodium alginate. The hardness of the CCCTs was 5.63–1.98 kgf, friability was 0.00–1.22%, and disintegration time was 0.00–401.25 min. Differential scanning calorimetry and Fourier-transform infrared spectroscopy indicated a high compatibility between the excipients and curcumin. CCCTs with chitosan formed a gel structure, impeded disintegration, and reduced the release rate to 72.5% in simulated gastric fluid. In simulated intestinal fluid, CCCT with the HPMC–sodium alginate group formed a polyelectrolyte membrane hydrogel to prolong release from 6 to 12 h. This study developed various CCCT formulations that can be delivered through the gastric or intestinal tracts, using chitosan and HPMC–sodium alginate as excipients, respectively. CCCT can be used as a reference strategy for controlled-release curcumin delivery in the functional and healthcare supplement development....
PROTACs, proteolysis targeting chimeras, are bifunctional molecules inducing protein degradation through a unique proximity-based mode of action. While offering several advantages unachievable by classical drugs, PROTACs have unfavorable physicochemical properties that pose challenges in application and formulation. In this study, we show the solubility enhancement of two PROTACs, ARV-110 and SelDeg51, using Poly(vinyl alcohol). Hereby, we apply a three-fluid nozzle spray drying set-up to generate an amorphous solid dispersion with a 30% w/w drug loading with the respective PROTACs and the hydrophilic polymer. Dissolution enhancement was achieved and demonstrated for t = 0 and t = 4 weeks at 5 ◦C using a phosphate buffer with a pH of 6.8. A pH shift study on ARV-110-PVA is shown, covering transfer from simulated gastric fluid (SGF) at pH 2.0 to fasted-state simulated intestinal fluid (FaSSIF) at pH 6.5. Additionally, activity studies and binding assays of the pure SelDeg51 versus the spray-dried SelDeg51-PVA indicate no difference between both samples. Our results show how modern enabling formulation technologies can partially alleviate challenging physicochemical properties, such as the poor solubility of increasingly large ‘small’ molecules....
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