Development of an intranasal formulation containing indomethacin and xylometazoline for rhinosinusitis treatment.

OBJECTIVE: Use of the nasal route of drug administration dates back many years and is used both to achieve topical treatments and to allow systemic absorption. The objective was to develop a formulation with novel features which enhance prolonged contact with the nasal and sinusal lining, since this should increase any therapeutic benefit. The anti-inflammatory drug selected was indomethacin, which was combined with xylometazoline, an effective nasal decongestant agent. MATERIALS AND METHODS: 28 Sprague-Dawley rats were used. They were then allocated at random to one of the four groups of equal size. All rats received a nasal application of 50mL of the platelet-activating factor solution at a concentration of 16 µg/mL and had induced rhinosinusitis. Indomethacin or xylometazoline HCl or both were dissolved in the oily phase of the solution and then a magnetic stirrer was used to homogenize the solution for 60 min at room temperature. All the O/W solutions exhibited stability and remained at neutral pH for the entire duration of the experiment. The only intervention was application of inactive 0.9% saline in group 1. The intervention was nasal application of xylometazoline and indomethacin in the combined formulation in group. The intervention was nasal application of xylometazoline only in group 3. The intervention was nasal application of indomethacin only in group 4. RESULTS: For the animals in group 1 (the controls), the mucosa had sustained a significant level of damage and the vessels were highly congested. Inflammatory cells were extensively infiltrating the mucosa. (Figure 1 - A1, 2, 3). In group 2, by contrast, the vessels were hardly congested and there were very few infiltrates. The epithelium appeared completely intact (Figure 1 - B1, 2, 3). Furthermore, when groups 1 and 2 were compared in terms of congested vessels, inflammatory cellular infiltrates and injury to the epithelium, the differences reached statistical significance, with p-values of <0.01, >0.001 and <0.001, respectively. Comparison of groups 2 and 4 with the control group also revealed statistically significant differences in terms of cellular infiltrates (p<0.001) and damage to the epithelium (p<0.001). For the degree of congestion of the vessels, however, the difference between groups was not at the level of statistical significance (p<0.071). Groups 3 and 4 differed at a statistically significant level in terms of degree of congested vessels, cellular infiltrates, and damage to the epithelium (p<0.025 and p<0.001). The sections from rats in groups 2 and 3 had a lower degree of congested vessels, which may be due to the actions of xylometazoline. CONCLUSIONS: In the future, topically applied intranasal NSAIDs will be valuable formulations. Innovative types of formulation, such as those demonstrating thixotropic behavior, permit the agent to remain in prolonged contact with the nasal and sinusal lining. Alongside increased efficacy, these preparations will also improve the side effect profile of NSAIDs, largely eliminating systemic effects.

Arsenic trioxide-loaded, microemulsion-enhanced cytotoxicity on MDAH 2774 ovarian carcinoma cell line.

The antiproliferative effect of As(2)O(3)-loaded microemulsion (As(2)O(3)-M) on human MDAH 2774 ovarian cancer cells was compared with a regular solution of the As(2)O(3). We used MDAH 2774 as model cell lines for ovarian cancer. The (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) (XTT) and trypane blue dye exclusion tests were used to evaluate cytotoxicity. Apoptotic effect of solutions was evaluated using cell death detection kit. Standard microemulsion formulation used in this experiment contains 5 x 10(-6) M As(2)O(3). It was clearly demonstrated that As(2)O(3)-M had a significant cytotoxic effect on MDAH 2774 cell line, and the cytotoxic effect of As(2)O(3)-M was significantly higher than that of regular As(2)O(3) solutions. Even approximately 6000 times diluted microemulsion formulation loaded with 5 x 10(-6) M As(2)O(3) showed a cytotoxic effect. As a result, this diluted concentration (approximately 8 x 10(-10) M) was found to be approximately 6000 times more effective than regular As(2)O(3) solutions (5 x 10(-6) M). Moreover, this diluted concentration resulted in 1.5-fold enhancement of apoptosis. According to the in vitro cytotoxicity studies, we concluded that by incorporating As(2)O(3) into the microemulsion (As(2)O(3)-M), which is a new drug carrier system, it is possible to increase antiproliferative effect of regular As(2)O(3) on MDAH 2774 cells. Translating these results to in vivo conditions would open new windows in the treatment of ovarian cancer.

Sustained-release dosage form of nitrofurantoin. Part 1. Preparation of microcapsules and in vitro release kinetics.

A new sustained-release dosage form of nitrofurantoin as microcapsules was prepared by carboxymethylcellulose-aluminium sulphate simple coacervation technique. In vitro release studies for microcapsules and their formulated hard gelatin capsule and tablet forms were performed. Release rates were studied as functions of core: wall ratios and the particle sizes of the microcapsules. Dissolution tests of microcapsules and their dosage forms were studied in simulated gastric and intestinal media without enzyme using the USP XXI basket method. Release data were examined kinetically and the ideal kinetic models were estimated for drug release. In addition, optical and electron scanning microscopic works were carried out on the microcapsules.