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.

Introduction: The hen's egg test on chorioallantoic membrane (HET-CAM) assay is a cost-effective and well-validated, non-animal-based ex vivo method for evaluating the irritant potential and eye toxicity of substances. A colloidal dispersion of a surfactant and a cosurfactant with a nanosize range is called a nanoemulsion (NE), which is formed by mixing immiscible liquids and stabilized by surfactants. Patients with glaucoma are commonly prescribed Brimonidine (BR), an alpha-2 adrenergic agonist, to lower their intraocular pressure. Materials and methods: In this study, surfactant-cosurfactant blends were prepared by mixing Tween 80 (surfactant) and propylene glycol (cosurfactant) in a 4:1(v/v) ratio. Triacetin served as the oil phase, while deionized water was used as the aqueous phase. Using the drop method, a range of NE formulations (F1, F2, F3, FB1, FB2, and FB3) were developed and subsequently evaluated for their potential to irritate, and then the results were compared to those of a commercially available BR eye drop formulation. Results: According to the average cumulative HET-CAM test scores (IS), from excipients, propylene glycol caused moderate irritation by causing slight damage to blood vessels. The formulations FB1 and F1 were found to have the highest level of irritation among other formulations in the investigation, recording 1.05 ±0.07 and 1.2 ±0.10, respectively. All other NE formulations exhibited non-irritating potential, as confirmed by the HET-CAM test, and were comparable to the marketed BR eye drop formulation. Conclusion: The NE formulations created for BR were determined to be safe and non-irritating. The findings indicate that the prepared NE could be a beneficial solution for addressing problems with conventional eye drops and delivering BR effectively to the eyes.

Background and objective: Low aqueous solubility of active pharmaceutical ingredients has an effect on both formulation development and bioavailability. Nimodipine is an antihypertensive agent with low oral bioavailability, which might be attributed to the extremely poor water solubility. This study aimed to increase the solubility of nimodipine in water using hydrotropes and solid dispersion technology to increase dissolution rate compared to the marketed drug product. Methods: Solubility of nimodipine was determined separately in sodium acetate, sodium citrate, sodium benzoate, and niacinamide solutions at a concentration of 10, 20, 30, and 40% w/v using distilled water as a solvent. The highest solubility was obtained in 40% sodium benzoate solution. Mixed concentrations of hydrotropic agents were used in ratio 1:3 (niacinamide: sodium benzoate). Fourier-transform infrared spectroscopy was used to exclude any drug-hydrotropes interaction. The dissolution rate of nimodipine from solid dispersion and physical mixture were studied using USP type II dissolution test apparatus in acetate buffer (pH 4.5) as a dissolution media. Results: Hydrotropic solid dispersion of nimodipine with a blend (30% sodium benzoate and 10% niacinamide) increased the dissolution rate of the drug by 1.5 folds compared to the marketed conventional nimodipine tablet. Fourier-transform infrared analysis did not show any physicochemical interaction between drug and carriers in solid dispersion formulation. Conclusion: The hydrotrop is a novel and safe compound. It is a successful way to enhance the solubility of poorly aqueous soluble drugs. Immediate dissolution of practically insoluble drug nimodipine in dissolution media indicates that it has a great potential to solubilize the drug in biological fluids. Thus, a considerable improvement in bioavailability and onset of action of the drug can be predictable. Adding of a hydrotropic agent with nimodipine in solid dispersion increased the dissolution rate of the drug compared to the marketed conventional nimodipine tablet Keywords: Hydrotropes; Nimodipine; Solubility enhancement; Solid dispersion.

The buccal delivery is an attractive route to improve the clinical efficacy of ropinirole hydrochloride (RH) for the treatment of Parkinson and restless syndrome since this drug undergoes extensive first-pass effect, which has only 50% bioavailability after oral administration. The purpose of this study was to develop and optimize the formulation of fast disintegrating buccal effervescent tablets of RH using four types of superdisintegrants. The direct compression method was used to develop four different formulas containing RH using Kyron T-314, crospovidone, croscarmellose sodium, and sodium starch glycolate separately as a superdisintegrant. Sodium bicarbonate and citric acid were added to the formulations to produce effervescence, while sodium carbonate was used as a pH adjusting agent. All the prepared formulas were evaluated, in terms of weight variation, friability, content dose uniformity, hardness, disintegration, and dissolution test. The best formulation was selected for the subsequent study. The obtained results from pre-compression studies were in acceptable range according to British Pharmacopoeia. All formulas passed through the quality control test and significant difference (P < 0.05) was observed for the formula four compared to other formulas, due to the presence of Kyron T-314 as a superdisintegrant in formulation number 4. RH cloud be prepared as a buccal effervescent tablet and superdisintegrant provide fast disintegration of the tablet to exert rapid action.