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Context: This study presents novel nanostructured oil-in-water (o/w) mists based on self-nanoemulsifying (SNE) mixtures capable of delivering poorly water-soluble drugs into the lungs. Objective: Formulation development of an o/w nanoemulsion (NE) capable of being nebulized for pulmonary delivery of poorly water-soluble drugs. Materials and methods: SNE mixtures were prepared and evaluated using Tween 80 and Cremophor RH 40 as surfactants; Transcutol P, Capryol 90 and PEG 400 as cosurfactants; and Labrafac Lipophile Wl 1349 (a medium-chain triglyceride) as an oil. Liquid NEs were analyzed by light scattering, zeta potential, transmission electron microscopy (TEM) and in vitro drug release studies. The aqueous NE was nebulized and assessed by light scattering and TEM. The formulation was aseptically filtered and the sterility validated. In vitro cytotoxicity of the formulations was tested in NIH 3T3 cells. The capability of the formulation to deliver a poorly water-soluble drug was determined using ibuprofen. Results: Ibuprofen was found to be stable in the NEs. The formulations were neutrally charged with a droplet size of about 20 nm. TEM images displayed 100 nm oil droplets. The aseptic filtration method produced sterile NE. The nebulized mist revealed properties ideal for pulmonary delivery. The biocompatible aerosol has a nanostructure consisting of several oil nanodroplets enclosed within each water drop. Solubility and in vitro drug release studies showed successful incorporation and release of ibuprofen. Conclusion: The developed formulation could be used as an inhalation for delivering material possessing poor water solubility into the lungs. [ABSTRACT FROM AUTHOR]

Context: Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. Objective: To prepare and characterise tamoxifen (TAM)-loaded SLNs. Materials and methods: Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Results: Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. Discussion: The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Conclusion: Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system. [ABSTRACT FROM AUTHOR]

Context: Water-in-oil microemulsions (w/o ME) are ideal for parenteral drug delivery. However, no such formulations have been tested for biocompatibility in in vitro cell cultures. Furthermore, sterilization of w/o MEs is a challenging process that has not been previously developed and validated. Purpose: To formulate pharmaceutically relevant water-in-oil (w/o) microemulsion's systems suitable for use as a parenteral formulation. Methods: w/o MEs were prepared using dioctyl sodium sulfosuccinate (DOSS), ethyl oleate (EO), and water. Formulations were characterized using polarized light microscopy, electrical conductivity, rheology, and dynamic light scattering. An aseptic filtration method for sterilization was developed using membrane filtration. The biocompatibility of selected MEs were evaluated in NIH3T3 cell cultures. Dissolution studies were performed on microemulsions containing methylene blue to evaluate the drug release profile. Results: The maximum amount of water incorporated in the formulations was 14% w/w. DOSS/EO/water microemulsions exhibited Newtonian flow. Particle sizes for these MEs were less than 30 nm in size. Formulations filtered aseptically were free of bacteria when gram-stained and visualized under a microscope. All MEs showed no toxicity to NIH 3T3 cells. Discussion: The absence of birefringence and low conductivity values indicated that the formulations were w/o microemulsions. The filtration method of sterilization was validated by the absence of microbial growth on blood agar plates over a 14-day period. In vitro dye release studies demonstrate sustained release of the model drug over a 72-h time period. Conclusion: Characteristics delineated in this study demonstrate the potential for these formulations to be used as parenteral preparations. [ABSTRACT FROM AUTHOR]

The first goal of this work was the preparation of a water-in-oil microemulsion from components generally regarded as safe for use in humans. Stable formulations without need of a co-surfactant were prepared from isopropyl myristate (IPM), dioctyl sodium sulfosuccinate (DOSS), and water. A ternary phase diagram was prepared for the IPM/DOSS/water system. The IPM/DOSS/water microemulsions were characterized by conductivity and dynamic laser light scattering (DLS). The results obtained from conductivity experiments indicate conductivity values of less than 1 μS/cm and were consistent with the formation of w/o microemulsions. The DLS results showed that the emulsified water droplets had an average diameter range of 9.2 to 19.7 nm, depending on composition. Modulation of the droplet size is possible by varying the water to DOSS molar ratio and DOSS to IPM ratio. The second goal of this work was the preparation of silver sulfadiazine (AgSD) nanoparticles. It was hypothesized that two separate microemulsions containing dispersed aqueous droplets of either sodium sulfadiazine or silver nitrate would react when mixed. The DLS results are consistent with the successful formation of submicron AgSD crystals. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1310–1320, 2005 [ABSTRACT FROM AUTHOR]