Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract
Bradley S. SimpsonXianling LuoJiping WangYunmei SongDavid ClaudieSanjay GargNicholas M. SmithRoss A. McKinnonSusan J. Semple
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Purpose: We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra. Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.Keywords:
Skin irritation
Anti-inflammatory
Ketorolac tromethamine[(+/-)-5(benzoyl)-2,3-dihydro-1N-pyrrolizine-1-carboxylic acid tris hydroxymethylaminomethane salt] is a highly potent member of a new class of compounds having analgesic and anti-inflammatory activity. When given orally in tests involving underlying inflammation it was a potent analgesic, whereas it was inactive in tests for narcotic activity. It was also highly active orally in rat models of acute and chronic inflammation and pyresis. These properties are mediated primarily via the compound's potent prostaglandin cyclooxygenase inhibitory activity. The agent elicited mild CNS and cardiovascular activity only at doses far in excess of those required for analgesic and anti-inflammatory activity. A single 10 mg tablet given orally to human volunteers following surgery provided pain relief equivalent to that provided by 10 mg of morphine given intramuscularly. When given intramuscularly to rabbits (0.25 ml of a 0.31-5% solution) or man (3 ml of a 1-3% solution), no drug-related irritation or changes in creatine phosphokinase were seen. Solutions (less than or equal to 0.5%) applied to the eyes of animals and man were not irritating. When applied topically in rat and rabbit models of ocular inflammation, less than or equal to 0.5% solutions of ketorolac tromethamine inhibited the inflammatory response.
Ketorolac Tromethamine
Diclofenac
Anti-inflammatory
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In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.
Flurbiprofen
Pharmacodynamics
Skin irritation
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Pankajakasthuri orthoherb cream/thermagel is a polyherbal topical medication formulated for managing inflammation and pain. The objective of the present study was to evaluate the skin irritation potential of Pankajakasthuri orthoherb cream/thermagel on a single and repeated application in New Zealand white rabbits. The rabbits were dermally exposed with Pankajakasthuri orthoherb cream/thermagel and the appearance of each application site at 1 h, 24 h, 48 h, 72 h, 7th day and 14th day was recorded. The dermal reactions (erythema and edema) were evaluated according to the skin reactions scoring system. Pankajakasthuri orthoherb
Erythema
Skin irritation
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Research on the development of dissolving microneedles (DMNs) has focused on bolus drug delivery, with little attention on sustained release. Here, we evaluated the sustained release, absorption pattern, and effective drug permeation of a novel donepezil-loaded DMN patch through an in vivo investigation on rats. The applications of DMN patches to the shaved skin of rats for 1 week and 1 h were compared with oral donepezil administration to assess their sustained release capabilities. We used a validated liquid chromatography-tandem mass spectrometry method to quantify donepezil in the plasma. We found that the microneedle arrays effectively delivered donepezil across the skin, with dissolution observed within 1 h of application. Furthermore, skin irritation test showed that the patches produced no irritation response. The DMN arrays also effectively increased drug permeation and demonstrated sustained release and absorption of donepezil from DMN patches. These patches allow extended dosing intervals, reduced gastrointestinal adverse effects, and convenient self-administration to mitigate poor drug compliance, making them beneficial for the treatment of elderly patients with Alzheimer's disease.
Skin irritation
Bolus (digestion)
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OBJECTIVE To study the anti-inflammatory and analgesic effects and irritant test of Qubi Zhitong gel,and to provide pharmacological reference for clinical application.METHODS The analgesic effect of Qubi Zhitong gel was tested by using the hot plate method and writhing method in mice; anti-inflammatory effect was studied by dimethylbenzene-induced ear tumefaction of mice; the skin-irritation test was investigated on rabbits with intact or traumatic skin.RESULTS The Qubi Zhitong gel could increase pain threshold in hot plate test,and reduce writhing times induced by acetic acid,and relieve the ear tumefaction induced by dimethylbenzene.No irritant response was observed in both the intact and traumatic skin.CONCLUSIONThe Qubi Zhitong gel has remarkable anti-inflammatory,analgesic effects,but no irritant action.The prospect of clinical application is expectable.
Hot plate
Anti-inflammatory
Hot plate test
Skin irritation
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Relative anti-inflammatory potencies of aspirin, phenylbutazone, indomethacin, three fenamates and several other nonsteroidal anti-inflammatory agents were obtained in several laboratory models of acute and chronic inflammation. Relative toxicities and ulcerogenicities were determined in rats of the same source, strain and sex. The acute ulcerogenic assay measures the minimal irritation potential of these agents and leads to a sensitive index of the safety of such compounds when compared with their therapeutic potencies. By these criteria, meclofenamic acid is a highly potent, acceptably safe and exceptionally well tolerated anti-inflammatory-antipyretic agent in rats when compared with other such drugs.
Anti-inflammatory
Antipyretic
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Objective To test the safety and anti-inflammatory action of extracts in root of Luffa cylin-drical.Methods The safety of Luffa cylindrical was tested by skin acute toxicity experiment,skin irritation experiment and acute toxicity experiment.The anti-inflammatory action was studied by through xylene-induced mouse auricle swelling experiment and carrageena-induced mouse paw swelling experiment.Results No irritation reaction occurred in complete skin after applied NiushangLingliniment many times and no reactions of occurred in injured skin.And the MTD is large.The drug could obviously inhibit xylene-induced mouse auricle swelling and carrageena-induced rat paw swelling.Conclusion The results indicated that the drug is safe and has obvious anti-inflammatory effects.
Auricle
Skin irritation
Anti-inflammatory
Inflammatory response
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Hairless
Skin irritation
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Securidaca longepedunculata is a plant commonly used by African populations. Previous works have identified the main bioactive constituents; study the toxicity, analgesic, anti-inflammatory, antioxidant activities of the root barks. This work aims at developing an Improved Traditional Medicine (ITM) in ointmentbased on the hydroethanolic extract of the root barks. The plant material was analyzed to determine the physicochemical parameters. The hydroethanolic extract was used to formulate ointments with shea butter. The quality parameters of the ointment were determined and the primary irritability was checked in albino rabbits. The local anti-inflammatory activity was evaluated against croton oil and xylem inflammation in mice. It exhibited stability at a temperature of 30°C and showed no skin irritation. It inhibited 27% of the inflammation to croton oil. Triterpenic saponins and antiradical constituents were the main chemical markers identified. These results and the existing data can be used for the development of “SECUDOL ointment”, an ITM against painful and inflammatory joint manifestations.
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Croton
Skin irritation
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Croton oil
Anti-inflammatory
Carrageenan
Skin irritation
Croton
Positive control
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