Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log P, and HLB on saturation solubility of KT. Hen’s Egg Test—ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log P and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log P. All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT.

Ropinirole hydrochloride (RH) is an anti-Parkinson drug with relativity low oral bioavailability owing to its extensive hepatic first pass metabolism. Spray-dried mucoadhesive alginate microspheres of RH were developed and characterized followed by histopathological evaluation using nasal tissue isolated from sheep. Spherical microparticles having high product yield (around 70%) were obtained when the inlet temperature of spray drying was 140 °C. Fourier Transform Infrared (FTIR) studies revealed the compatibility of the drug with the polymer, and scanning electron microscopy (SEM) showed that drug-loaded microparticles were spherical, and the apparent surface roughness was inversely related to the ratio of polymer to drug. Furthermore, size of the spray-dried particles were in the range of 2.5 - 4.37 µm, depending on formulation. All formulations had high drug encapsulation efficiencies (101 - 106%). Drug loaded into the polymeric particles was in the amorphous state and drug molecules were molecularly dispersed in the polymeric matrix of the microparticles which were revealed by X-ray diffraction and differential scanning calorimetry (DSC), respectively. The in vitro drug release was influenced by polymer concentration. Histopathological study demonstrated that RH-loaded sodium alginate microparticles was safe to nasal epithelium. In conclusion, spray drying of RH using sodium alginate polymer has produced microparticles of suitable characteristics for potential intranasal administration.

Purpose. The biopharmaceutics classification system places rosuvastatin calcium in class II has a low and fluctuating oral bioavailability. The research focus is to maximize rosuvastatin calcium solubility in water and dissolution rate by employing and combining various hydrotropic agents to make a solid dispersion using solvent evaporation techniques. Methodology. The experimental study was conducted at Duhok University, College of Pharmacy. Initially, assess rosuvastatins solubility in hydrotropic agents including urea, mannitol, citric acid, sodium benzoate, and sodium salicylate at concentrations of 10, 20, 30, and 40 w/v. Then, various ratios of 2 and 3 hydrotropic agents were employed to reduce the concentration of each hydrotropic agent. By using a solvent evaporation procedure, solid dispersions were made. The solid dispersion powders underwent evaluation for their percentage drug content, percentage yield, solubility, dissolution test, XRD, DSC, SEM, and FTIR. For statistical analysis, GraphPad InStat Demo software was used to conduct a two-way analysis of variance (ANOVA). Results. In comparison to the pure drug, the solubility of hydrotropic solid dispersions and physical mixtures of rosuvastatin with a combination of hydrotropic agents (sodium salicylate, sodium benzoate, and urea) in the ratio of 13.33 for each increased in all formulations significantly, and all manufactured formulations drug release ranged from 98.83 to 104.78, indicating a noticeably higher dissolution rate. Conclusion. The concept of mixed hydrotropic solid dispersion was shown to be an original, risk-free, and cost-effective method for enhancing the bioavailability of drugs that have a low degree of solubility in water.

Background/Objectives: This study aimed to fabricate, optimize, and characterize nanostructured lipid carriers (NLCs) loaded with trans-resveratrol (TRES) as an anti-cancer drug for pulmonary drug delivery using medical nebulizers. Methods: Novel TRES-NLC formulations (F1–F24) were prepared via hot, high-pressure homogenization. One solid lipid (Dynasan 116) was combined with four liquid lipids (Capryol 90, Lauroglycol 90, Miglyol 810, and Tributyrin) in three different ratios (10:90, 50:50, and 90:10 w/w), with a surfactant (Tween 80) in two different concentrations (0.5 and 1.5%), and a co-surfactant, soya phosphatidylcholine (SPC S-75; 50 mg). Results: Amongst the analyzed 24 TR-NLC formulations, F8, F14, and F22 were selected based on their physicochemical stability when freshly prepared and following storage (4 weeks 25 °C), as well as in terms of particle size (<145 nm), polydispersity index (PDI; 96%). Furthermore, F14 showed greater stability at 4 and 25 °C for six months and exhibited enhanced aerosolization performance, demonstrating the greater deposition of TRES in the later stages of the next-generation impactor (NGI) when using an air-jet nebulizer than when using an ultrasonic nebulizer. The F14 formulation exhibited greater stability and release in acetate buffer (pH 5.4), with a cumulative release of 95%. Conclusions: Overall, formulation F14 in combination with an air-jet nebulizer was identified as a superior combination, demonstrating higher emitted dose (ED; 80%), fine particle dose (FPD; 1150 µg), fine particle fraction (FPF; 24%), and respirable fraction (RF; 94%). These findings are promising in the optimization and development of NLC formulations, highlighting their versatility and targeting the pulmonary system via nebulization.

Aerosolization is a non-invasive approach of delivering drugs for both localized and systemic effects, specifically pulmonary targeting. The aim of this study was to deliver trans-resveratrol (TR) as an anti-cancer drug entrapped in a new generation versatile carriers nanostructured lipid carrier (NLC) to protect degradation and improve bioavailability via medical nebulizers. Twelve TR-NLC (i.e., F1-F12) formulations were prepared using different combinations and ratios of formulation ingredients via hot high-pressure homogenization. Upon analysis, formulations F1 and F2 demonstrated a particle size of <185 nm, a polydispersity index (PDI) 94%. The aerosolization performance of the F1 and F2 formulations was performed via a next generation impactor (NGI), using medical nebulizers. The air jet nebulizer demonstrated lower drug deposition in the earlier stages (1-2) and significantly higher deposition in the latter stages 3-5 (for both formulations), targeting middle to lower lung deposition. Moreover, the air jet nebulizer exhibited significantly higher emitted dose (ED) (87.44 ± 3.36%), fine particle dose (FPD) (1652.52 ± 9.68 µg) fine particle fraction (FPF) (36.25 ± 4.26%), and respirable fraction (RF) (93.41 ± 4.03%) when the F1 formulation was used as compared to the F2 formulation. Thus, the TR-NLC F1 formulation and air jet nebulizer were identified as the best combination for the delivery and targeting peripheral lungs.

Gliclazide (Glz) is a second-generation sulfonylurea antidiabetic drug, used to treat type II diabetes mellitus. Glz is a class II drug according to the biopharmaceutic classification system (BCS), indicating that it has high permeability and poor aqueous solubility. This study aimed to improve the solubility of Glz via the solid dispersion method. Solid dispersions of the drug were formulated using carboxymethyl chitosan (CMch) and polyvinyl pyrrolidone K30 (PVP K30) in varying drug to carrier ratios (1:1, 1:3, and 1:5 w/w) using kneading and solvent evaporation methods. The solubility of Glz solid dispersions was compared with the pure Glz and co-grounded mixtures of the drug. Both carriers exhibited a noticeable increment in solubility and dissolution rate compared to the drug alone. Glz: CMch (1:5 w/w ratio) formulation made by the kneading method exhibited an increased solubility by approximately 9 folds (337.79 ± 4.22 µg/ml) as compared to Glz alone (38.74 ± 4.69 µg/ml). However, the greatest improvement in drug dissolution rate was observed in the dispersion made with 1:5 w/w drug to PVP K30 using the solvent evaporation method, and the percentage drug release reached 100% after 30 min. Solid dispersions characterization manifested the compatibility between the drug and carriers, with alteration in particle morphology, and reduction in drug crystallinity. Overall, solid dispersion using CMch has shown to be an excellent approach for enhancing the solubility and dissolution of the class II drug Glz.