Anti-inflammatory Formulations Research Articles

Development and evaluation of curcumin-loaded elastic vesicles as an effective topical anti-inflammatory formulation.

Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux - 0.46 ± 0.02 μg/h/cm(2)) was compared with curcumin-loaded EVs (flux - 4.14 ± 0.04 μg/h/cm(2)). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p < 0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.

Development and characterization of two nano-structured systems for topical application of flavanones isolated from Eysenhardtia platycarpa

Many of the inflammatory diseases are becoming common in ageing society throughout the world. The clinically used anti-inflammatory drugs suffer from the disadvantage of side effects. Alternative to these drugs are natural products, since ancient times traditional medicines are being used for the treatment of inflammation. In the present study, four flavanones isolated from Eysenhardtia platycarpa leaves with a potent pharmacological activity were formulated in effective drug delivery systems: nanoemulsion and polymeric nanoparticles for topical use as novel anti-inflammatory topical formulations. Nanoemulsion system exhibited droplet sizes less than 70nm and polymeric nanoparticles with a size of 156–202nm possessed zeta potential values less than −25mV that provided good stability and obtained high entrapment efficiency (78–90%). In vitro release and ex vivo permeation studies were performed on Franz-type diffusion cells and quantified by high performance liquid chromatography (HPLC), all formulations showed steady state release profiles over time and steady increase of flavanones in the skin permeation test. The anti-inflammatory activity, tested by TPA (12-O-tetradecanoylphorbol-13-acetate), induced oedema in mice ear suggesting that prenylated flavanones improve significantly their anti-inflammatory activity when are vehiculized in nanosized systems. Our results suggested that 5-hydroxy-7-methoxy-6-prenyl flavanone loaded nanoemulsion and polymeric nanoparticle could be proposed as potential topical anti-inflammatory formulations with the best properties for the treatment of inflammatory disorders.

Faster, higher, stronger? Evidence for formulation and efficacy for ibuprofen in acute pain

A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better analgesia than standard ibuprofen as the free acid. We examined several lines of evidence to investigate what benefit derived from fast-acting formulations. A systematic review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that median maximum plasma concentrations of fast-acting formulations occurred before 50min (29–35min for arginine, lysine, and sodium salts) compared with 90min for standard formulations. An updated analysis of clinical trials (over 10,000 patients) showed that fast-acting formulations produced significantly better analgesia over 6h and fewer remedications than standard formulations in both indirect and direct comparisons. In dental studies, 200-mg fast-acting ibuprofen (number needed to treat 2.1; 95% confidence interval 1.9–2.4) was as effective as 400 mg standard ibuprofen (number needed to treat 2.4; 95% confidence interval 2.2–2.5), with faster onset of analgesia. Individual patient data analysis in dental pain demonstrated a strong correlation between more rapid reduction of pain intensity over 0–60min and better pain relief over 0–6h. Rapid initial reduction of pain intensity was also linked with reduced need for remedication. Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. Achieving a better analgesic effect with fast-acting nonsteroidal anti-inflammatory drug formulations has important implications for safety. Formulation chemistry is of potential importance for analgesics.

The Pharmacology of Topical Analgesics

Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain – whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic – a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal anti–inflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti–inflammatory drug formulations produce a site–specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co–formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding systemic circulation, topically applied analgesics are associated with application–site reactions in patients, such as dryness, erythema, burning, and discoloration. Furthermore, some adverse events that have been observed in patients may be suggestive of some degree of systemic exposure. This article reviews the mechanisms of action, pharmacokinetics, and tolerability of topical treatments for the management of patient pain.

Bicellar systems as new delivery strategy for topical application of flufenamic acid

In this work, bicellar systems, bilayered disc-shaped nanoaggregates formed in water by phospholipids, are proposed as a novel strategy for delivery of the anti-inflammatory flufenamic acid (FFA) to the skin. A comparative percutaneous penetration study of this drug in bicellar systems and other vehicles was conducted. The effects induced on the skin by the application of FFA in the different vehicles were analyzed by attenuated total reflectance-fourier transform infrared (ATR-FTIR). Additionally, using the microscopic technique freeze-substitution transmission electron microscopy (FSTEM) and X-ray scattering technique using synchrotron radiation (SAXS-SR), we studied the possible microstructural and organizational changes that were induced in the stratum corneum (SC) lipids and the collagen of the skin by the application of FFA bicellar systems. Bicellar systems exhibited a retarder effect on the percutaneous absorption of FFA with respect to the other vehicles without promoting disruption in the SC barrier function of the skin. Given that skin disruption is one of the main effects caused by inflammation, prevention of disruption and repair of the skin microstructure should be prioritized in anti-inflammatory formulations.

Chemiluminescence determination of ibuprofen and ketoprofen using the Fenton system in the presence of europium(iii) ions

A simple new chemiluminescent method for the determination of ibuprofen (IB) and ketoprofen (KP) is described. The method for the determination of ibuprofen is based on the europium(III) emission as a result of the energy transfer process from the excited product of the ibuprofen oxidation in the Fenton system to the uncomplexed Eu(III). The detection limit of ibuprofen is 6 × 10−8 mol L−1. The method was successfully applied to the determination of IB in a mixture of non-steroidal anti-inflammatory drugs, pharmaceutical formulations and urine.

Standardization of the finished product: Habbe Irqun Nisa - A Unani anti-inflammatory formulation

Background:Habb (Pill) is one of the important dosage forms of Unani system of medicine. A number of effective formulations are manufactured in form of Habb because of its various advantages. Out of these, Habbe Irqun Nisa (HI) is a popular anti-inflammatory formulation used in the treatment of Warame Mafasil (arthritis) and Irqun Nisa (sciatica). Nowadays, with increased incidence of these diseases many non-steroidal anti-inflammatory drugs (NSAIDs) are being used in their treatment. Owing to the adverse effects of these drugs, the use of herbal medicines is seen as a better alternative. The basic requirement for the development of Unani system of Medicine is the standardization of single and compound drugs. HI is mentioned in National Formulary of Unani Medicne and selected for the present study.Materials and Methods:HI was prepared manually with the powder of crude drugs, passed through sieve no. 100 and mixed with 1% w/w of gum acacia in mucilage form. It was then dried at 60°C for 90 min and then tested for its standardization on different physicochemical parameters, e.g. organoleptic properties, pH values, moisture content, ash values, friability, hardness, weight variation, disintegration time, and thin layer chromatography (TLC).Results and Conclusion:The data evolved from this study will make it a validated product and will help in the quality control of other finished products in future research.

Interesting effect of Malassezia spp. infection on dermatoses of other origins

Tinea versicolor (TV) is a superficial fungal infection affecting as many as 40% of the population in the tropics. We noticed an unusual affect of TV on dermatoses of other origins. In this prospective clinical study, we examined patients attending our dermatology outpatient department over a period of one year for coexistence of TV with any unrelated dermatoses. We confirmed the diagnosis of TV by microscopy of skin scrapings. Skin biopsy was performed when necessary to confirm the diagnosis of associated dermatoses. We describe four cases in which unrelated dermatoses (viral exanthem, acute generalized exanthematous pustulosis, polymorphous light eruption, and irritant contact dermatitis) specifically spared sites affected with TV. Recent research has elucidated the immunomodulatory properties of Malassezia spp. in vitro. Our cases serve as possible in vivo models illustrating such properties. Further studies based on these reports could lead to the isolation of molecules from Malassezia, which may have potential use in anti-inflammatory drug formulations.

Genetic Variability in Germplasm Accessions of &amp;lt;i&amp;gt;Capsicum annuum&amp;lt;/i&amp;gt; L

Capsicum annuum is the most widely cultivated species of peppers (chilies) in the world. For culinary purposes, its fruits are used for pungency (capsaicin) and also color (capsanthin). Capsaicin is also used for medicinal purposes particularly in anti-inflammatory formulations. Genetic divergence among 38 accessions collected from diverse locations in India (28 from Uttar Pradesh, 5 from Assam, 3 from Maharashtra and 2 from Uttaranchal), was estimated from the data pooled over 3 consecutive years for 15 morphological, growth and chemotypic characters that included days to first and second flowering, fruit onset, plant height, primary, secondary and tertiary branches, leaf surface area, fruit length and diameter, fruit surface area, fresh and dry fruit weight, capsaicin and capsanthin content. Based on this characterization the plants could be grouped into 7 clusters wherein substantial diversity among accessions was indicated by the wide range of D2 values (752.901 - 1918683.00). Accessions with distinct identity were marked, which are likely to be quite suitable for breeding through hybridization combining desirable traits. The accessions labeled number 38, 27, 26, 14 and 24 to high capsaicin content (%); 35, 23, 3, 16, 29 and 11 for high capsanthin content (%) and 26 and 27 for dual purpose had characteristics desirable. Above accessions could be utilized in hybridization programme for C. annuum crop improvement.

Development of inhalable formulations of anti-inflammatory drugs to potentially treat smoke inhalation injury in burn victims

Injury arising from smoke inhalation is a significant mortality risk in severe burned patients. Inflammatory processes are major contributors to the development of respiratory insufficiency owing to pulmonary oedema, formation of airway fibrin clots and hypoxaemia. Anti-inflammatory and anti-coagulant drugs such as heparin and pentoxifylline are currently systemically administered for the treatment of smoke inhalation. Delivery of these drugs in the form of inhalable particles could be an effective manner to achieve rapid targeted action for acceleration of the treatment. The study developed and characterised a series of spray-dried heparin and pentoxifylline dry powder formulations suitable for inhalation administration. Drug particles were co-spray-dried with leucine in varying ratios. Particle size analysis confirmed all powders (except 2%, w/w, pentoxifylline with 1%, w/w, leucine in spray-drying feed solution) had particle size in the optimal range (≤5 μm) for deep lung drug deposition. Leucine supplementation dramatically altered heparin surface topography while pentoxifylline formulations were a mixture of elongated needles interspersed with wrinkly particles. Addition of leucine improved fine particle fraction of heparin and pentoxifylline. The study indicated manufacture of inhalable heparin and pentoxifylline was feasible and can potentially be an attractive delivery alternative to the more conventional systemic delivery route.

Artificial Light-Induced Cytokine Gene Expression in Rabbit Cornea in vivo: Effect of Ocular Drops Containing Flurbiprofen

The purpose of this study is to examine the effect of artificial sunlight on the gene expression of TNF-α, IL-6 and IL-8 in rabbit cornea in vivo, as well as the potential of an ocular anti-inflammatory formulation containing sodium flurbiprofen to suppress this effect. New Zealand Albino rabbits were subjected to acute exposure of their eyes to irradiation emitted from a light bulb commonly used for artificial tanning purposes with and without topical application of a commercially available formulation containing sodium flurbiprofen. Semi-quantitative RT-PCR was used as a means of estimating gene expression. The gene expression of IL-6 and IL-8 was found statistically significantly increased at 24 hrs post-exposure time (p = 0.003 and 0.006, respectively), as was that of TNF-α albeit in a non-statistically significant manner. A sodium flurbiprofen (0.03%) formulation was found to effectively reduce the light-induced upregulation of all three cytokines in the rabbit cornea.

Short communication: Topical and Oral Anti-Inflammatory Formulations Containing Extracts of Ficus racemosa Linn. Leaves

The anti-inflammatory activity of petroleum ether and alcoholic extracts of Ficus racemosa Linn. leaves has been reported. Oral and topical formulations containing different concentrations of these extracts were developed and evaluated for their anti-inflammatory activity by carragenan-induced rat paw oedema method. The effects of the preparations were observed for 6 h. Among the topical formulations prepared, 10% w/w of the petroleum ether extract exhibited the maximum (67.96%) anti-inflammatory effect at the end of 3 h. Oral suspensions of both the petroleum ether and alcoholic extracts, at doses of 100 mg/kg body weight, exhibited less anti-inflammatory activity than the topical preparation, i.e. 57.88% and 50.62% at the end of 3 h, respectively. However, these activities were comparable to that of the marketed oral and topical preparations of diclofenac salts. Keywords: anti-inflammatory activity, Ficus racemosa, topical formulation, oral suspensions, carragenan-induced rat paw oedemaEthiopian Pharmaceutical Journal Vol. 25 (2) 2007: pp. 151-155

Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology

Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. Qing-Kai-Ling is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection. In this paper, we report that one of the components of Qing-Kai-Ling, Fructus gardeniae, strongly inhibits MMP activity. The IC 50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 μg/ml, respectively. In addition, we show that the herbal extracts influence HT1080 human fibrosarcoma cell growth and morphology. These data may provide molecular mechanisms for the therapeutic effects of Qing-Kai-Ling and herbal medicinal Fructus gardeniae.

Antioxidative and gastroprotective activities of anti-inflammatory formulations derived from chestnut honey in rats

Drug formulations Alimento Supervis (AS) and Alimento Mieleucalipto (AM), which are derived from chestnut honey, have been used as vehicle and supplemented with ginseng, propolis, royal jelly and propolis, and eucalyptus, respectively. These substances are traditionally used as anti-inflammatory medicine and were commercialized before conducting preclinical studies on their efficacy. The antioxidant properties of AS, AM, honey, and their respective natural components were determined by H 2O 2/luminol-derived and superoxide/lucigenin-derived chemiluminescence. AS and AM scavenged both superoxide anions and hydrogen peroxide more than did honey. The H 2O 2-scavenging activity of each natural component decreased in the following order: propolis > eucalyptus > ginseng >> royal jelly. O 2 −-scavenging activity was practically absent for all components, except for propolis, the activity that proved to be strongest. Oral pretreatment of AS, AM, and honey (2 g/kg), once daily for 7 consecutive days, prevented indomethacin-induced gastric lesions in rats by reducing the ulcer index, microvascular permeability, and myeloperoxidase activity of the stomach.

New anti-inflammatory formulation containingSynurus deltoides extract

Synurus deltoides was previously found to possess significant anti-inflammatory activity especially against chronic inflammation, and strong analgesic activity in vivo. In this study, new anti-inflammatory formulation containing S. deltoides extract as a major ingredient was prepared and in vivo activity was evaluated. The plausible action mechanism was also investigated. The new formulation (SAG) contains 1 part of S. deltoides extract, 0.9 part of Angelica gigas extract and 0.9 part of glucosamine sulfate (w/w). SAG inhibited dose-dependently edematic response of arachidonic acid (AA)- and 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema in mice, which is an animal model of acute inflammation. SAG showed 44.1% inhibition of AA-induced ear edema at an oral dose of 50 mg/kg. In an animal model of chronic inflammation, SAG clearly reduced the edematic response of 7-day model of multiple treatment of TPA (38.1% inhibition at 200 mg/kg/day). Furthermore, SAG (50-800 mg/kg/day) as well as S. deltoides extract (285 mg/kg/day) significantly inhibited prostaglandin E2 production from the skin lesion of the animals of 7-day model. These results were well correlated with in vitro finding that SAG as well as S. deltoides extract reduced cyclooxygenase (COX)-1- and COX-2-induced prostanoid production, measured in mouse bone marrow-derived mast cells. Therefore, these results suggest that SAG possesses anti-inflammatory activity in vivo against acute as well as chronic inflammatory animal models at least in part by inhibition of prostaglandin production through COX-1/COX-2 inhibition. And COX inhibition of SAG is possibly contributed by S. deltoides extract among the ingredients. Although the anti-inflammatory potencies of SAG were less than those of currently used anti-inflammatory drugs, this formulation may have beneficial effect on inflammatory disorders as a neutraceutical.

Use of densitometric TLC for detection of selected drugs present in river water in South Poland

The steadily increasing consumption of popular drugs (e.g. common anti-bacterial, anti-convulsant, anti-hallucinatory, anti-inflammatory, and analgesic formulations) prescribed both in human and veterinary medicine (and sometimes available even without medical prescription) results in growing contamination of the environment by these substances and their metabolites. This contamination is naturally directed through the rivers to the seas and oceans and tends to accumulate in these terminal reservoirs. It was the aim of the work discussed in this paper (i) to establish a simple yet efficient solid-phase extraction (SPE) method for isolation of the drugs josamycin, sulfamethoxazole, carbamazepine, diclofenac, and iopromide from aqueous matrices; (ii) to quantify these compounds by use of densitometric TLC; and (iii) to test the method by applying it to environmental samples (river water from South Poland). The results obtained clearly demonstrate that SPE combined with densitometric TLC is highly suited to this analytical task.

Analysis of Asthma-Related Costs and Patterns of Resource Utilization in a Managed-Care Population

Objectives: To identify the asthma prevalence rate, the total healthcare and asthma-related treatment costs, and the medical and pharmacy costs associated with different asthma medication usage patterns in a managed-care organisation (MCO). Study design and participants: The medical and pharmacy claims databases from a 400 000 member MCO were used. The medical claims database was searched from 1994 to 1996 for patients having at least one asthma medical claim in either the first or second diagnosis field of the medical claims, and the total healthcare and asthma-related costs were determined. A subpopulation with a more restrictive asthma definition was identified and their costs were also determined. In addition, the patterns of drug treatment were identified. Study perspective: MCO perspective. Results: The mean total healthcare cost of caring for patients with asthma was significant and approximately twice the mean cost of all patients enrolled in the MCO. Using a broad definition of asthma, the mean (± standard deviation) annual total per patient healthcare cost was $US2511 ± 7314 and the annual asthma-related cost was $US679 ± 2247 (1996 values). Using a more restrictive definition of asthma, the mean annual total per patient healthcare cost was $US2653 ± 5268 and the asthma-related cost was $1026 ± 2447. There appeared to be a low overall use of asthma medications, especially anti-inflammatory formulations; <3% of patients with asthma were high users of anti-inflammatory inhalers. Conclusions: Patients with asthma are costly to managed-care organizations. Asthma-related costs constitute a minority (<30%) of the costs of caring for these patients, and under utilization of anti-inflammatory products by patients is widespread. Further research is needed to assess the cost impact of different asthma treatment patterns.

Combinations of antiviral and anti-inflammatory preparations for the topical treatment of herpes simplex virus assessed using a murine zosteriform infection model.

Recently we have reported a zosteriform murine infection model which employs the adoptive transfer of immune cells (ATI) to recipient infected mice to produce a disease that mimics human recurrent herpes simplex virus (HSV) disease. Mice were infected with HSV-1 by scarification at the lateroventral line of the neck; 2 days later, the mice received immune cells from HSV-1-infected syngeneic mice. Although virus was cleared more quickly from the target tissues of virus replication in recipient mice, ATI resulted in a heightened inflammatory response and delayed healing. This model was used to test the effects of topical formulations containing foscarnet and/or the anti-inflammatory agent, hydrocortisone. Virus clearance and clinical signs, including ear thickness and zosteriform spread of lesions, were studied. Treatment with 3% foscarnet accelerated virus clearance but had little effect on clinical parameters. By contrast, 0.5% hydrocortisone increased the titre and extended the presence of infectious virus for at least 6 days, although the reduction in clinical signs was greater than that obtained with topical foscarnet. Foscarnet in combination with hydrocortisone produced a marked reduction in clinical signs while virus replication was reduced. These results are discussed in relation to the inflammation and discomfort experienced by patients and a possible role for anti-inflammatory formulations in the treatment of HSV reactivation episodes in man.

Quantitative assessment of non-steroidal anti-inflammatory topical products in nicotinate-induced erythema using tristimulus colour analysis

The activities of several proprietary non-steroidal anti-inflammatory topical preparations in nicotinate-induced skin inflammation were studied in two comparative trials using a tristimulus colour analyzer: the first to observe intra-individual variation in a single subject and the second to study inter-subject variation with six volunteers. Objective parameters were derived from the prolonged multiple-point chromaticity coordinate a∗ values obtained after occlusion. Statistical evaluation (ANOVA and Tukey's multiple-range test) of these parameters was performed. Using those parameters, non-steroidal anti-inflammatory formulations could be ranked according to their efficacies in suppressing the nicotinate-induced erythema.

Comparative efficacy and tolerability of two antibacterial/ anti-inflammatory formulations (‘Otomize’ spray and ‘Otosporin’ drops) in the treatment of otitis externa in general practice

An open, multi-centre study was carried out in general practice to compare the efficacy, tolerability and acceptability of a neomycin/dexamethasone preparation administered by spray ('Otomize') and neomycin/polymyxin B/hydrocortisone administered as drops ('Otosporin') in the treatment of 187 patients with otitis externa. Patients were allocated at random to receive one or other preparation 3-times daily for 10 days irrespective of response and were followed up again 14 days after cessation of therapy. Assessments were made on entry and at Days 10 and 24 of the severity of erythema, swelling and debris. A global assessment of clinical outcome was made by the doctor on Day 10. There were no significant differences between the two groups at the start of treatment. Significant improvement occurred in both groups from Day 0 to Day 10 and from Day 10 to Day 24 in all symptoms, but no statistically significant differences were recorded between the two drugs. However, significantly more patients in the 'Otomize' group were rated as having a good clinical outcome by the physicians, and a highly significant number of patients, with previous experience of the use of ear drops, expressed a preference for the spray preparation. Few side-effects were reported by either treatment group, none necessitating discontinuation of therapy.