A new and simple reverse phase high performance liquid chromatography method was developed for the simultaneous determination of the major compounds of skin-whitening pharmaceutical cream, i.e., two active pharmaceutical ingredients: hydroquinone and kojic acid, two sunscreens: octinoxate and avobenzone and two antioxidants: butylated hydroxyanisole and butylated hydroxytoluene. Separation was achieved on a Zorbax SB-Phenyl (250 × 4.6 mm; 5 μm) column, using a mobile phase consisting of water with 0.1% acetic acid and acetonitrile, in a dual-mode gradient for 14 minutes. The column was maintained at 40 °C and detection was carried out at 230 nm by using a diode-array detector. The extraction procedure was studied by a design of experiments demonstrating its suitability. The structure of an additional unknown peak eluting in all chromatograms in the same proportion was identified by HPLC/MS as the keto tautomer of avobenzone. The method developed was successfully validated in accordance with ICH guidelines with regard to selectivity, linearity, accuracy, precision and robustness. Selectivity was found to be satisfactory. The linear regression analysis data for all compounds showed a good linear relationship with r² > 0.999 in the concentration range from 50% to 120% of the label claimed for each compound. The percentage RSD for precision and accuracy of the method was found to be less than 2% for all compounds. The proposed method was applied for the determination of six major compounds in skin-whitening cream prototypes developed during the formulation development stage.

Background: Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs.
Aim: The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN–nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods: Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results: We obtained nanoparticles with a mean diameter of approximately 150–200 nm in size and zeta potential values of 25–40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA- and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion: The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery.

Hydrophilic matrix tablets are a type of sustained release dosage form characterized by distributing a drug in a matrix that is usually polymeric. Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase. In recent years, it has been shown that tolcapone is a potent inhibitor of the amyloid aggregation process of the transthyretin protein, and acts by stabilizing the structure of the protein, reducing the progression of familial amyloid polyneuropathy. The main objective of this study was to obtain a sustained release tablet of tolcapone for oral administration with a preferred dosage regimen of 1 administration every 12 or 24 h and manufactured, preferably, by direct compression. The SeDeM Diagram method has been used for the formulation development of hydrophilic matrix tablets. Given the characteristics of tolcapone, the excipient selected for the formation of the polymeric matrix was a high viscosity hydroxypropylmethylcellulose (Methocel^® K100M CR). A decrease in the particle size of tolcapone resulted in a slower dissolution release of the formulation when the concentration of the polymer Methocel^® K100M CR was below 29%. These surprising and novel results have given rise to patent number WO/2018/019997.

A previously published HPLC method for the simultaneous determination of six major components (hydroquinone, kojic acid, octinoxate, avobenzone, butylated hydroxyanisole, and butylated hydroxytoluene) in a skin-whitening cream was transferred and optimized to an ultra-performance LC system. Separation was achieved in a ZORBAX SB-Phenyl Rapid-Resolution High Throughput column (2.1 × 100 mm, 1.8 μm), using a mobile phase consisting of water with 0.1% acetic acid and acetonitrile at a flow rate of 0.7 mL/min. The column was maintained at 40°C, and detection was carried out at 230 nm using a diode-array detector. These chromatographic conditions allow the separation of the six compounds in 3 min instead of 14 min. The extraction procedure was optimized, reducing the time and demonstrating its suitability. The method was validated according to International Conference on Harmonization guidelines, with respect to specificity, precision, accuracy, and linearity. Selectivity was found to be satisfactory. Linear regression analysis data for all compounds showed a good linear relationship, with r² > 0.999 in the concentration range of 50–120% of the label claim for each compound. The RSD for precision and accuracy of the method was found to be less than 2% for all compounds. Comparison of system performance with the previously published HPLC method was made with respect to analysis time, efficacy, and resolution. The proposed method is faster and consumes less solvent and was applied in the determination of six major compounds in batches of skin-whitening cream manufactured during the validation process.