Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability

Solid Dispersion Pellets: An Efficient Pharmaceutical Approach to Enrich the Solubility and Dissolution Rate of Deferasirox

Deferasirox (DFX) is an oral iron-chelating agent and classified into class II of the Biopharmaceutics Classification System. Low bioavailability of the drug due to insufficient solubility in physiological fluids is the main drawback of DFX. The idea of the current study was to explore the potential of solid dispersion (SD) as an effective method to improve the dissolution rate of DFX in pellets. The SDs were made by the solvent evaporation technique using polyethylene glycol 4000 (PEG 4000) and polyvinylpyrrolidone K25 with different drug-to-carrier ratios. Then, the dispersion was milled and mixed with other components and the mixture layered on sugar-based cores by pan coating technique. The pellets were evaluated in terms of size distribution, morphology (SEM), and dissolution behaviour. Drug-polymer interactions were studied using differential scanning calorimetry (DSC), X-ray diffraction study (XRD), and Fourier transformation infrared (FTIR) spectroscopy. The pellets coated with SD showed a remarkable rise in the solubility of DFX than that of free drug-loaded pellets. The dispersion with PVP K25 showed a faster dissolution rate as compared to other mixtures. The DSC and XRD analysis indicated that the drug was in the amorphous state when dispersed in the polymer. The FTIR studies demonstrated any ruled out interaction between drug and polymer. The SEM showed smoothness on the surface of the pellets. It is resolved that the SD method considerably enriched the dissolution rate of DFX in pellets, which can also be utilized for other poorly water-soluble drugs

Preparation and Characterization of Paracetamol Solid Dispersions Using Opened Ring PVP and PEG 4000

Background & Objective: Solid dispersions (SDs) have been traditionally used as an effective method for improving the dissolution properties and bioavailability of poorly water-soluble drugs. The aim of this study was to improve the solubility and dissolution rate of paracetamol by SD technique. Materials & methods: The prepared SDs were evaluated by saturation solubility test, In-vitro drug release test, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). Results: The prepared SDs exhibited a statistically significant increase in the solubility of paracetamol compared to that of the free drug (p < 0.05). After 15 min SD tablets had an enhanced cumulative drug release compared to tablets of the free drug (p < 0.05). FTIR study revealed that paracetamol was stable in polymeric dispersions. DSC and SEM microscopy showed that the drugs crystallinity was decreased during the preparation process (amorphous crystal formation). Conclusion: The FTIR spectroscopic test revealed the presence of intermolecular hydrogen bonding between paracetamol and the polymers in the SDs, which could increase the aqueous solubility of the drug. The DSC analysis indicated that the drug was in the amorphous state when dispersed in the polymers. Dissolution studies indicated that the dissolution rates were markedly increased in the SDs compared with those of paracetamol alone, and Better results were obtained with PVP K25

Effects of Magnesium-Vitamin E Co-supplementation on Glucose Metabolism, Oxidative Stress, and Pregnancy Outcomes Among Women with Gestational Diabetes: A Double-blind Clinical Trial Study

Background & Objective: Dietary antioxidants may play a protective role in the pathophysiology of gestational diabetes mellitus (GDM). The present study aimed to evaluate the effect of magnesium-vitamin E co-supplementation on glycemic control and pregnancy outcomes in women with GDM. Materials & Methods: This randomized clinical trial was conducted among GDM pregnant women at 24-28 weeks of gestation. The study did not include mothers who needed medication to control their blood glucose levels or had a history of DM. The subjects were randomly divided into two 30-member groups, one of which received magnesium (250 mg), and vitamin E (400 mg) daily, while the other was given a placebo. Blood samples were taken at the study baseline and six weeks after the intervention to quantify oxidative stress biomarkers, fasting plasma glucose (FPG), and fasting plasma insulin (FPI). Additionally, the effect of supplementation was assessed on neonatal outcomes. Data analysis was performed using SPSS 20 (SPSS, Chicago, IL) Results: A significant decrease was observed in the FPG and FPI of the supplementation group (p<0.05). However, FPI elevated by progressing pregnancy in the placebo group (p=1.99×10-4). The homeostasis model assessment (HOMA) revealed that supplementation was associated with improved insulin sensitivity (p=3.38×10-13). In addition, total antioxidant capacity increased to 5.66 ± 0.86% in the treatment group. Finally, no significant difference was found between the groups regarding neonatal outcomes. Conclusion: The results represented that magnesium-vitamin E co-supplementation significantly reduced oxidative biomarkers and improved glycemic control in GDM

Antibacterial Activities of Gel Containing 5% Hydroalcoholic Extract of Rhamnus cathartica L. bark

Background and purpose: Acne is a chronic inflammatory disease of the pilosebaceous glands caused by opportunistic microorganisms. The Rhamnus cathartica is known to have biological and antioxidant properties. This research aimed at investigating the in vitro effect of gel containing 5% R. cathartica extract on acne vulgaris. Materials and methods: The gel formulation contained 25g of dried R. cathartica bark extract, 0.5 liters distilled water, glycerin 50g, carbopol 940 5g, methyl paraben 0.75g, and propyl paraben 0.5g. After 24 hours, the formulation was put outside the refrigerator. Then, triethanolamine was added to the formulation under stirring with 500 rpm to solidify the gel. The effect of the product was measured against Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus and MIC and MBC values were also determined. Results: Total phenolic content of R. cathartica was 351.6±4.5 mgGA/g/DW, total flavonoid content was 23.15±1.355 mgCE/g/DW, and total anthraquinone content was 1.85 ± 0.05 mgAE/g/DW. The pH of the product was 5.5-6. The MIC values of R. cathartica 5% gel were 195.3 µg/ml, 24.41 µg/ml, and 97.65 µg/ml against C. acnes, S. epidermidis and S. aureus, respectively. The MBC testing showed 25000 µg/ml, 25000 µg/ml, and 12500 µg/ml against C. acne, S. epidermidis and S.aureus. Conclusion: R. cathartica is believed to contain active ingredients and can act as an antibiotic against acne causing microorganisms