METHODS: A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel.

RESULTS: After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae.

METHODS: The review protocol was registered in the PROSPERO database (CRD42017071899). A literature search was performed in the MEDLINE and EBSCOhost databases until June 2017 with no language restriction. Randomized controlled trials evaluating the efficacy of oral premedications, whether given alone or in combination, compared with other agents, placebo, or no treatment in adult patients before NSRCT for postoperative pain were included. Nonintervention studies, nonendodontic studies, animal studies, and reviews were excluded. The quality of the studies was assessed using the revised Cochrane risk of bias tool. Pair-wise meta-analysis, network meta-analysis, and quality of evidence assessment using the Grading of Recommendations Assessment, Development and Evaluation criteria was performed.

RESULTS: Eleven studies comparing pharmacologic groups of medications were included in the primary analysis. Compared with placebo, corticosteroids (prednisolone 30-40 mg) was ranked best for reducing postoperative pain (median difference [MD] = -18.14 [95% confidence interval (CI), -32.90 to -3.37] for the pain score at 6 hours; MD = -22.17 [95% CI, -36.03 to -8.32] for the pain score at 12 hours; and MD = -21.50 [95% CI, -37.95 to -5.06] for the pain score at 24 hours). However, the evidence was very low (6 and 24 hours) to moderate quality (12 hours). Nonsteroidal anti-inflammatory drugs were ranked least among the medications, and the quality of this evidence was very low. Additional analysis based on the chemical name showed that sulindac, ketorolac, and ibuprofen significantly reduced pain at 6 hours, whereas piroxicam and prednisolone significantly reduced the pain at 12 and 24 hours. Etodolac was found to be least effective in reducing pain. Overall, the evidence was of moderate to very low quality.