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Traumatic brain injury (TBI) is an incurable and overwhelming disease accompanied with serve disability and huge financial burden, where the overproduced reactive oxygen species (ROS) can exacerbate the secondary injury, leading to massive apoptosis of neurons. In this study, β-cyclodextrin (CD)-capped hyperbranched polymers containing selenium element (HSE-CD) were crosslinked with CD-modified hyaluronic acid (HA-CD) and amantadine-modified hyaluronic acid (HA-AD) to obtain a ROS-responsive ointment (R-O). The structures of synthesized polymers were characterized with 1H nuclear magnetic resonance, and the properties of ointment were investigated with rheology and antioxidation. Compared to non-ROS-responsive ointment (N-O), the R-O ointment had stronger efficiency in decreasing the ROS level in BV2 cells in vitro. In a controlled rat cortical impact (CCI) model, the R-O ointment could relieve the DNA damage and decrease apoptosis in injured area via reducing the ROS level. Besides, after the R-O treatment, the rats showed significantly less activated astrocytes and microglia, a lower level of pro-inflammatory cytokines and a higher ratio of M2/M1 macrophage and microglia. Moreover, compared to the TBI group the R-O ointment promoted the doublecortin (DCX) expression and tissue structure integrity around the cavity, and promoted the recovery of nerve function post TBI. Traumatic brain injury (TBI) is an incurable and overwhelming disease, leading to severe disability and huge social burden, where reactive oxygen species (ROS) are considered as one of the most significant factors in the secondary injury of TBI. A ROS responsive supramolecular ointment containing di-selenide bonds was injected in rats with controlled cortical impact. It relieved the DNA damage and decreased apoptosis in the injured area via reducing the ROS levels, downregulated neuroinflammation, and improved neurological recovery of TBI in vivo. This designed self-adaptive biomaterial effectively regulated the pathological microenvironment in injured tissue, and achieved better therapeutic effect. [Display omitted] [ABSTRACT FROM AUTHOR]

Wound healing poses a challenging therapeutic scenario, requiring diverse clinical approaches. This study aims to assess the wound-healing potential of Salix aegyptiaca' s flower ointment compared to phenytoin, considering the active constituents of S. aegyptiaca and its traditional usage. Initially, the active components of S. aegyptiaca were isolated and identified through the GC-MS technique. Subsequently, for the experimental intervention, thirty-five rats were divided into five distinct groups: control (C), phenytoin (F), and three S. aegyptiaca ointment groups at different concentrations (5 % - S5, 25 % - S25, and 50 % - S50). Anesthesia was administered, and wounds were induced on the animals' necks following a standard procedure. These wounds were then treated for a duration of 21 days. Wound healing progress was quantified, and histopathological assessments were conducted using hematoxylin and eosin staining and Mason's trichrome staining. The main active compounds of S. aegyptiaca , namely n-hexadecanoic acid and oleic acid, were identified via GC-MS analysis. Although the initial group weights did not show a significant difference (P = 0.271), a significant variation was observed in the final weights (P = 0.003). The S50 group exhibited a lower wound healing rate than the S25 group on the 7th and 14th days but surpassed it on the 21st day (C < F < S5≈S25

Safe and effective long-term topical treatments for atopic dermatitis (AD) remain limited. In this phase 2a, single-center, intrapatient, and vehicle-controlled study, we examine the mechanism of action of crisaborole 2% ointment, a topical nonsteroidal PDE4 (phosphodiesterase-4) inhibitor, in a proteomic analysis of 40 adults with mild to moderate AD and 20 healthy subjects. Within the AD cohort, 2 target lesions were randomized in an intrapatient (1:1) manner to double-blind crisaborole/vehicle applied twice daily for 14 days. Punch biopsy specimens were collected for biomarker analysis at baseline from all participants, then from AD patients only at day 8 (optional) and day 15. Compared to the vehicle, crisaborole significantly reversed dysregulation of the overall lesional proteome and of key markers and pathways (eg, Th2, Th17/Th22, and T-cell activation) associated with AD pathogenesis toward both nonlesional and normal skin. Significant clinical correlations were observed with markers associated with nociception and Th2, Th17, and neutrophilic activation. Study limitations include predominance of white patients in the cohort, relatively short treatment time, and regimented administration of crisaborole. Our results demonstrate crisaborole-induced normalization of the AD proteome toward a nonlesional molecular phenotype and further support topical PDE4 inhibition in the treatment of mild to moderate AD. [ABSTRACT FROM AUTHOR]

[Display omitted] Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Background: Delgocitinib 0.5% ointment, a topical Janus kinase inhibitor, has been approved in Japan for adult patients with atopic dermatitis (AD).Objective: To evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD.Methods: Part 1 of this study was a 4-week double-blind period in which Japanese patients aged 2 through 15 years were randomized in a 1:1 ratio to delgocitinib 0.25% ointment or vehicle ointment. Part 2 was a 52-week extension period. Eligible patients entered part 2 to receive 0.25% or 0.5% delgocitinib ointment.Results: At the initiation of the study, approximately half of the patients had moderate AD. At the end of treatment in part 1, the least-squares mean percent change from baseline in modified Eczema Area and Severity Index score, the primary efficacy endpoint, was significantly greater for delgocitinib ointment than for vehicle (-39.3% vs +10.9%, P < .001). In part 2, improvements in AD were also seen through week 56. Most adverse events were mild and unrelated to delgocitinib across the study periods.Limitations: Only Japanese patients were included. In part 2, no control group was included and rescue therapy was allowed.Conclusion: Delgocitinib ointment was effective and well tolerated when applied to Japanese pediatric patients with AD for up to 56 weeks. [ABSTRACT FROM AUTHOR]

There are no strict pH standards for herbal formulations; however, pH can affect the characteristics of drugs and herbal formulations. In this study, the pHs of different herbal formulations produced in the past two batch years at the Centre for Plant Medicine Research (Mampong-Akuapem, Ghana) were analysed. We aimed to evaluate pH consistency among the formulations and suggest suitable pH ranges for the different product classes. The formulations analysed were 17 decoctions, three ointments, and nine powders. Suitable ointment and powder samples were prepared before pH was measured, whereas decoctions were analysed directly. We found that 93.1% of the preparations had average pH < 7 over the two years. The pH values for the decoctions, ointments, and powders were 3.507−6.755, 5.153−5.700, and 5.413−10.719, respectively. Differences in pH over the two production years were not statistically significant for all the powder and ointment formulations as well as for majority of the decoctions (82.4%). This indicates pH consistency for approximately 90% of the products, possibly pointing to consistencies in plant material compositions, formulation conditions, and process parameters. From our data and reported literature, we recommend that the labels of oral herbal preparations with pH < 5.5 should include an instruction to dilute the product before intake, or to drink water or rinse the mouth after intake to prevent enamel erosion. Decoctions may also be taken after food. Additionally, pH ranges of 4.6−7.0 and 4.0−6.0 may be suitable for rectal and topical herbal formulations, respectively. [ABSTRACT FROM AUTHOR]

The usefulness of topical antibiotic prophylaxis for routine oculofacial plastic surgery is not well established. Given concerns such as contact dermatitis, antibiotic resistance, and healthcare costs in conjunction with a low baseline rate of surgical site infections, the investigators sought to determine the frequency of infection with and without the use of topical antibiotic prophylaxis. Randomized, controlled, unmasked clinical trial. Adult patients undergoing routine periocular surgery without prior history of periocular surgical site infection, need for perioperative oral or parenteral antibiotics, or allergy to all study medications. Participants were randomized before surgery to receive either antibiotic or placebo (mineral oil and petrolatum-based) ointment after surgery. Outcomes were measured at the first postoperative visit. The 2-tailed Fisher exact test was used to compare outcomes between groups. The primary outcome was the incidence of surgical site infections. The secondary outcomes included stratification of infections by patient risk characteristics, incidence of allergic contact dermatitis, and incidence of wound complications. Four hundred one participants were enrolled and randomized, and 13 participants did not proceed with surgery or were lost to follow-up. High-risk features for infection were identified in 24% of the placebo group and 21% of the antibiotic group. Surgical site infections were more common in the placebo group (2.7% vs. 0.0%; P = 0.025). The rate of contact dermatitis was similar (0.5% vs. 0.5%; P = 1.00), as was the rate of wound dehiscence (2.7% vs. 3.5%; P = 0.77). Among the placebo group, the incidence of infections in the low- and high-risk participants was 2.9% and 2.2%, respectively. Infections were treated with oral or topical antibiotics and resolved without complication, except in 1 patient who required 2 subsequent surgeries to address the sequelae. After routine oculofacial plastic surgery, patients treated with a topical antibiotic ointment showed a lower risk of surgical site infection compared with patients treated with a nonantibiotic ointment. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed the potential effectiveness of delgocitinib ointment, a novel topical Janus kinase inhibitor, in atopic dermatitis (AD).Objective: This study aimed to evaluate the efficacy and safety of delgocitinib 0.5% ointment.Methods: In part 1, a 4-week double-blind period, Japanese patients aged 16 years or older with moderate or severe AD were randomly assigned in a 2:1 ratio to delgocitinib 0.5% ointment or vehicle ointment. Eligible patients entered part 2, a 24-week extension period, to receive delgocitinib 0.5% ointment.Results: At the end of treatment in part 1, the least-squares mean percent changes from baseline in the modified Eczema Area and Severity Index score, the primary efficacy endpoint, were significantly greater in the delgocitinib group than in the vehicle group (-44.3% vs 1.7%, P < .001). The improvement in modified Eczema Area and Severity Index score was maintained in part 2. Most adverse events were mild and unrelated to delgocitinib across the study periods.Limitations: Only Japanese patients were included. The vehicle-controlled period lasted only 4 weeks. In part 2, topical corticosteroids were allowed for the treatment of worsening of AD.Conclusion: Delgocitinib ointment was effective and well tolerated in Japanese adult patients with moderate to severe AD for up to 28 weeks. [ABSTRACT FROM AUTHOR]

Topical delgocitinib (JTE-052), a novel Janus kinase inhibitor, had been shown to be clinically effective in adults with atopic dermatitis (AD). However, the efficacy of topical delgocitinib in pediatric patients with AD remained unclear. We sought to evaluate the efficacy and safety of delgocitinib ointment in pediatric patients with AD. In this phase 2 clinical study (JapicCTI-173553) Japanese patients aged 2 through 15 years with AD were randomized in a 1:1:1 ratio to receive 0.25% or 0.5% delgocitinib ointment or vehicle ointment twice daily for 4 weeks. The primary efficacy end point was the percentage change from baseline in the modified Eczema Area and Severity Index score at the end of treatment (EOT). At EOT, modified Eczema Area and Severity Index scores in both delgocitinib groups were significantly reduced compared with that in the vehicle group. The least-squares mean percentage change from baseline was −54.2% in the 0.25% group and −61.8% in the 0.5% group versus −4.8% in the vehicle group (P <.001 for both comparisons). Similarly, all other efficacy parameters, including Investigator's Global Assessment and pruritus scores, in both delgocitinib groups were significantly improved compared with those in the vehicle group at EOT. Adverse events in both delgocitinib groups were mild in severity, and no serious adverse events were reported. Delgocitinib ointment improved clinical signs and symptoms in pediatric patients with AD and was well tolerated. These study results indicate that delgocitinib ointment can be a promising therapeutic option for pediatric patients with AD. [ABSTRACT FROM AUTHOR]

Background: The superficial lymphatic component of vascular malformations poses a significant treatment challenge. It is responsible for the majority of symptoms presented, and to date, there is no consensus regarding treatment.Objective: To evaluate the effectiveness of topical rapamycin in treating superficial lymphatic malformations (LM).Methods: A case series study was performed of patients with superficial LM, treated with topical rapamycin. The clinical characteristics of patients and the concentration and application mode of the drug were recorded. The changes in the signs and symptoms observed and associated adverse effects were noted and analyzed.Results: The study population consisted of 11 patients of an average age of 10.5 years. All were treated with topical rapamycin: 6 patients with a 1% concentration, 1 with a 0.8% concentration, and 4 with a 0.4% concentration. Changes in the clinical appearance of the lesions were observed in all patients. The associated symptoms, present in 9 of 11 patients, improved in every case. The mean follow-up time was 16.1 months.Limitations: This study is retrospective, with a small sample size and considerable heterogeneity of lesions and treatment approaches.Conclusion: Treatment with topical rapamycin modifies the clinical appearance and alleviates symptoms of superficial LM. [ABSTRACT FROM AUTHOR]

Aims: Diabetes induces various skin troubles including foot ulcer. This type of skin ulcer is refractory but the pathogenesis is not so certain. Recent study show that glucagon-like peptide-1 (GLP-1) analogues reduce foot complications with diabetes (Pérez et al., 2015), however, the role of GLP-1/GLP-1R axis is not fully understood, and clear evidence of GLP-1 to facilitate wound closure is still lacking. In this study, we investigated whether a potent GLP-1R agonist liraglutide affects wound healing process.Methods: The expression of GLP-1R in HaCaT cells were indentified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunoblotting analysis. To assess the effect on wound closure in keratinocytes, we performed in vitro scratch assay using the IncuCyte system (Essen BioSciences, Ann Arborm MI). We applied ointment containing liraglutide on full-thickness wounds in the dorsum of female balb/c mice (n = 6) until healing. To investigate the effect on PI3K/Akt pathway, we used IncuCyte system in HaCaT treated with PI3K inhibitor and Akt inhibitor.Results: Keratinocytes expressed GLP-1R and liraglutide induced their migration. Liraglutide facilitated the wound healing in mice. Liraglutide upregulated keratinocyte migration via PI3K/Akt activation.Conclusions: Our study suggests that liraglutide may be a potential target drug to improve skin ulcer with diabetes through its specific receptor GLP-1. [ABSTRACT FROM AUTHOR]

The copper-coated iron oxide nanoparticles with core-shell were produced by deposition of a Cu shell on Fe 3 O 4 NPs through reduction of Cu 2+ ions in solution using NaBH 4 . Subsequently, the organosulfur compound, bis-(2,4,4-trimethylpentyl)-dithiophosphinic acid (b-TMP-DTPA), was used to form self-assembled monolayer in order to modify sorbent's surface via covalent bonding between Cu and thiol (–SH) terminal groups. The prepared magnetic nanoparticles were characterized by using Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), vibrating sample magnetometer (VSM) and thermo gravimetric analysis (TGA). Then, the application of this new sorbent was investigated to extract the steroid drugs in ointment samples with the aid of ultrasound. An external magnetic field was applied to collect the magnetic nanoparticles (MNPs). The extracted analytes were desorbed using acetonitrile. The obtained extraction solution was analyzed by HPLC-UV. The main affecting factors on the extraction efficiency including pH, sonication time, amount of sorbent, salt concentration, and desorption conditions were optimized in detail. Under the optimum conditions, good linearity was obtained in the range of 2.5–250.0 µg/ L with reasonable linearity (R 2 > 0.99) and the limits of detection (LODs) ranged between 0.5 and 1.0 µg/L (based on S/N = 3). Repeatability (intra-day precision) based on five replicates and preconcentration factors were calculated to be 3.6%–4.7% and 87–116, respectively. Relative recoveries in ointment samples at two spiked levels of the target analytes were obtained in the range of 90.0%–103.2%. The results illustrated that the Fe 3 O 4 @Cu@ b-TMP-DTPA NPs have the capability of extraction of steroid drugs from ointment samples. [ABSTRACT FROM AUTHOR]

Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations. [ABSTRACT FROM AUTHOR]

A stability indicating high performance liquid chromatography method has been developed for the determination of triamcinolone acetonide (TCA) and its main degradation products in ointment formulations. The method, based on extensive stress testing using metal salts, azobisisobutyronitrile, acid, base and peroxide, showed that TCA undergoes oxidative degradation. All degradation products were identified using HPLC mass spectrometry. Separation and quantification was achieved using an Altima C18 RP18 HP column (250 × 4.6 mm 2 , with 5 μm particles) using a mobile phase consisting of acetonitrile and water buffered at pH 7 using 10 mM phosphate buffer. A gradient mode was operated at a flow rate of 1.5 ml/min and detection was at 241 nm. The method showed linearity for TCA and Impurity C in 0.02–125% of the workload, both square roots of the correlation coefficients were larger than 0.9999. Repeatability and intermediate precision were performed by six consecutive injections of both 1.25% and 125% of the work load for both TCA and Impurity C divided equally over two days. RSD were 0.6% and 0.7% for TCA and 0.5% and 0.1% for Impurity C respectively. Accuracy was determined as well, the average recoveries were 99.5% (±0.1%, n = 3) for TCA and 96.9% (±1.3%, n = 3) for impurity C respectively from spiked ointment samples. The robustness was also evaluated by variations of column (old vs new), mobile phase pH and filter retention. The applicability of the method was evaluated by analysis of a commercial ointment formulation. Interestingly, the extensive stress tests were able to predict all degradation products of TCA in a long term stability ointment sample. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new thiophene based fluorescent receptor has been synthesized for the specific detection of Ag+ ions. • The synthesized receptor (ADC) was characterized by NMR and mass spectroscopic techniques. • The detection limit (LOD) was calculated to be 4.98 µm and the limit of quantification (LOQ) as 6.36 µm for the sensing of Ag+ ions by receptor ADC. • The complexation was confirmed through 1H NMR titration, IR spectra and DFT analysis. • Strip paper, cotton swab, ointment, water sample experiments and bio-imaging were carried out for the detection of Ag+ ions utilizing ADC. A simple thiophene based chalcone as fluorescent receptor (ADC) was synthesized by Claisen Schmidt condensation method upon linking 2-acetyl thiophene (1) and N,N -dimethylamino benzaldehyde (2). The synthesized receptor is well characterized by NMR, IR, and mass spectroscopic techniques. The ADC receptor was examined for the detection of metal ions, in which it had a noticeable blue shifted fluorescence enhancement for Ag+ ions. Upon binding towards Ag+ ions, the photoinduced electron transfer (PET) process is inhibited via intramolecular charge transfer (ICT) process taking place. The binding stoichiometry of ADC + Ag+ complexation ratio is noted to be 2:1, which was further confirmed by jobs plot method, 1H NMR titration, IR spectral analysis, and DFT studies. The limit of detection (LOD) and limit of quantification (LOQ) was found to be 4.98 µm and 6.36 µm respectively. Additionally, ADC showed color changes upon binding with Ag+ ions in strip paper, cotton swab test through UV-365 nm illumination. Moreover, ADC was successfully utilized for the practical applications of Ag+ ion detection in water samples, ointment and bacterial cell lines. [ABSTRACT FROM AUTHOR]

The delayed onset of monoaminergic antidepressants and disadvantages of traditional administration routes created the need for alternative non-invasive delivery methods with rapid onset therapeutic effect. Ketamine attracted attention as a fast-acting glutamatergic antidepressant with ideal physiochemical properties for alternative routes of administration. However, there is no sufficient data for its transdermal use in depression. In this proof-of-concept study, we investigated the antidepressant effects of transdermal ketamine delivered via a novel ointment with skin protective, emulsifying and permeation enhancing properties. A shea butter-based 5% (w/w) ketamine ointment or a drug-free vehicle ointment were applied to the shaved dorsal skin of male Wistar rats for 2 days, twice a day. Behavioral despair, locomotor activity and anxiety-like behavior were respectively assessed in the forced swim test (FST), open field test (OFT), and elevated plus maze (EPM). The pharmacokinetic profile of the ointment was analyzed with high-performance liquid chromatography. Transdermal ketamine ameliorated behavioral despair without altering general locomotor activity and anxiety-like behavior, showing that skin-friendly drug carriers like shea butter may constitute promising alternatives to current routes of delivery for ketamine. Tested transdermal method aims to provide more sustainable drug delivery for long-term treatment schedules. Future studies can investigate its long-term use, side effects and abuse liability. • A shea butter-based 5% (w/w) ketamine ointment was prepared. • The ointment was applied to the shaved dorsal skin of adult male Wistar rats (2 ×2). • The pharmacokinetic profile of the ointment was analyzed with HPLC. • Transdermal ketamine led to an antidepressant effect in the forced swim test. • It did not alter general locomotor activity or anxiety-like behavior. [ABSTRACT FROM AUTHOR]

The healing effects of silver and gold nanoparticles (AgNPs, AuNPs) are already known from ancient times. In addition considering to their antibacterial and anti-inflammatory effects speculations are being lead with respect to these nanoparticles (NPs) also about enhancement of skin penetration properties. In this work the interactions of pig skin (PS) layers and ointments with additions of AgNPs or AuNPs prepared by standard procedures and also by “green” synthesis in a different weight proportion by vibrational spectroscopy were studied. Spectra of untreated skin and skin treated by pure ointment were measured, as well as by ointment modified by vitamins without addition of NPs or with different proportion of NPs. Kinetics of interactions of modified ointments with skin was monitored during two hours with a five-minutes interval between each two consecutive measurements. The obtained series of spectra were analyzed by multivariate statistical methods namely Partial Least Squares (PLS), Principal Component Analysis (PCA) and Soft Independent Modelling of Class Analogy (SIMCA) which revealed observation of spectral changes in time-dependent spectra and variations of the peak intensity ratios. The study showed that the effects of quantity and type of NPs on skin penetration characteristics are evident. [ABSTRACT FROM AUTHOR]

Batch-to-batch variability is a challenge for the industrial scale production of ointments. Therefore the current investigation focussed on identifying and understanding critical process parameters (CPPs) for cetomacrogol ointment. This was evaluated using a definitive screening design (DSD) approach in which fourteen batches were produced under predefined and controlled conditions using the following variables: addition of SiO 2 nanoparticles, mixing speed, cooling rate, heating temperature, container filling temperature and isothermal mixing at the filling temperature. Ointment structure was evaluated using a number of rheological parameters. One of these parameters, yield stress was found to be strongly influenced by filling temperature and mixing speed (p = 0.0065 and p = 0.0013 respectively). Both significantly affect ointment structure and they also have a significant interaction (p < 0.05). Understanding the ointment production process can help in defining a processing window to produce ointment of constant quality. [ABSTRACT FROM AUTHOR]

A method for quantitative determination of ibuprofen (IBU), naproxen (NAP), methyl salicylate (MES) and menthol (MNT) in commercial topical gels and ointments using partial least squares (PLS) models based on FT-Raman spectra is described. The calculated relative standard errors of prediction (RSEP) were found to be in the range of 2.1–3.2% for the calibration and validation data sets. Two commercial topical gels containing 5.0% of IBU and 10% of NAP (w/w), as well as one ointment containing 15% of MES and 10% of MNT (w/w) as active pharmaceutical ingredients (APIs), were successfully quantified using the developed models with recoveries in the 99.2–101.5% range. The proposed procedure can be used as a fast, reliable and economic method for the quantification of APIs in topical gels and ointments. [ABSTRACT FROM AUTHOR]

This work demonstrates the development of nitric oxide-releasing ointment and its potential on efficient wound healing. Nitric oxide-releasing polymer was successfully synthesized, which is composed of biocompatible Pluronic F127, branched polyethylenimine and 1-substituted diazen-1-ium-1,2-diolates. The synthesized nitric oxide-releasing polymer was incorporated into the PEG-based ointment which not only facilitated nitric oxide release in a slow manner, but also served as a moisturizer to enhance the wound healing. As compared to control groups, the nitric oxide-releasing ointment showed the accelerated wound closure with enhanced re-epithelialization, collagen deposition, and blood vessel formation in vivo . Therefore, this nitric oxide-based ointment presents the promising potential for the efficient strategy to heal the cutaneous wound. [ABSTRACT FROM AUTHOR]

In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time. [ABSTRACT FROM AUTHOR]

Highlights: [•] Biosynthesis of AgNPs (72–98nm) using leaf extracts of Naringi crenulata leaf via microwave irradiation method was established. [•] FTIR, XRD results confirmed the presence of bioactive compounds in leaf extracts responsible for reduction of AgNO3. [•] Synthesized AgNPs based ointment showed potential wound healing activity in experimental rats. [ABSTRACT FROM AUTHOR]

The phytochemical analysis of the investigated Immortelle essential oil revealed the presence of monoterpenes and sesquiterpenes as major components that might be efficient as a wound healing potential agent. The present study aimed to develop an ointment based on the Immortelle essential oil and investigate its wound healing effects on excision wounds in diabetic rats. The topical formulated Immortelle ointment was subjected to pharmaco-technical characterization. Thirty-two diabetic rats with the induced excision wound were used to evaluate in vivo wound healing effects of ointment. The animals were randomly divided into four groups untreated or topically treated with either a 1% silver sulfadiazine, the ointment base, or Immortelle ointment. The response to the treatment was assessed by macroscopic, biochemical and histopathological analysis. The ointment, compatible with the skin remained stable for 6 months. Topical application of the Immortelle ointment showed the highest wound contraction with the highest content of hydroxyproline in comparison to the all examined groups. The Immortelle ointment showed significant wound contraction from day 7 to day 21 as compared to other groups. On the day 21, there was an average of 99.32% wound contraction in the Immortelle group, whereas the mean wound contraction in the negative control and ointment base group was 71.36% and 81.26% respectively. The histopathological results validated the potential wound healing effect of Immortelle ointment with evident post-excision scar maturation and increased collagen fibers density. Our findings revealed that the Immortelle ointment approach might serve as a promising and innovative tool for wound healing. [Display omitted] • Immortelle ointment remained stable for 6 months. • The rheological behavior followed a non-Newtonian pseudoplastic pattern. • Immortelle ointment did not show any signs of dermal irritation. • Administration of Immortelle ointment increases wound contraction in rats. • Immortelle ointment accelerates wound healing by stimulating collagen deposition. [ABSTRACT FROM AUTHOR]

Highlights: [•] Efficacy and safety of methimazole ointment on hyperthyroidism was observed. [•] Methimazole ointment has similar clinical efficacy as oral tablets. [•] Methimazole ointment causes fewer systemic adverse effects. [ABSTRACT FROM AUTHOR]

In dermatology, ointments are often mixed as part of drug therapy, but mixing often leads to incompatibility. Three combinations of tetracycline ointment (TC-o) and acyclovir cream (ACV-cr) were prepared at a TC-o:ACV-cr ratio of 1:1 using a brand-name ACV-cr and two generic ACV-cr (samples TC-o+ACV-A, TC-o+ACV-B, and TC-o+ACV-C). Microscopic examination revealed separation in TC-o+ACV-C. Viscosity and elasticity measurement indicated that the storage modulus (G′) and loss modulus (G″) of each of the TC-o+ACV-cr mixtures behaved similarly to those of an ACV-cr and the loss tangent (tan δ) behaved similarly to that of a TC ointment. In addition, differences in the storage modulus (G′) and loss modulus (G″) of the TC-o+ACV-cr mixtures were noted. To assess stability, each TC-o+ACV-cr mixture was stored away from direct sunlight at 25°C and an RH of 84% and at 4°C (in a refrigerator). HPLC revealed that the ACV content in each TC-o+ACV-cr mixture remained at 95–105% for up to 14 days under both sets of storage conditions. A decline in TC content in each TC-o+ACV-cr mixture was not noted with storage at 4°C but was noted over time with storage at 25°C and an RH of 84%. In addition, significant differences in the percent decline in TC content in each TC-o+ACV-cr mixture occurred with storage at 25°C and an RH of 84%. Thus, differences in physical properties and stability may occur when combining brand-name and generic drugs, and temperature and humidity may be the cause of the TC-o's incompatibility. [ABSTRACT FROM AUTHOR]

Abstract: Background: Statins represent a class of drugs that effectively lowers cholesterol, however they also possess pleiotropic effects, like promotion of angiogenesis, prevention of bone loss, immunomodulatory and anti-inflammatory effects. Objectives: Thus, the aim of this study was to investigate the activity of simvastatin topically applied in mice in acute and chronic skin inflammation models. Methods: Skin inflammation was induced in mice ears by topical application of 12-O-tetradecanoylphorbol acetate (TPA). In the acute model, ear oedema was measured by the increase of ear thickness 6h after TPA (2.5μg/ear). The chronic inflammatory process was induced by multiple applications of TPA (2.0μg/ear) for nine alternate days, and the oedema was measured daily as the increase in ear thickness. Results: Topical treatment was applied immediately after TPA in acute model or started at 5th day of chronic experiment. For acute model treatment was simvastatin (0.24, 0.71 and 2.40μM), dexamethasone (0.13μM), both in acetone or vehicle alone (acetone). In chronic model simvastatin (1% and 3%) and dexamethasone (0.5%) were incorporated in ointment preparations, and a group received ointment alone (vehicle). Samples of ear tissue (6mm) were taken from acute and chronic models, weighted and prepared for histological analysis and myeloperoxidase (MPO) enzymatic activity evaluation. Application of simvastatin in acetone reduced the ear oedema after a single TPA application in a dose dependent manner [ID50 of 0.47 (0.22–1.13) μM], and the MPO enzymatic activity up to 61±10%. Also, both simvastatin ointment preparations 1% and 3% reduced acute TPA-induced ear oedema in 55±7% and 65±8%, respectively. In the chronic model, simvastatin ointment 1% was able to reduce ear oedema (25±3%) and ear weight (10±1%), though 3% formulation augmented both parameters. Histological analysis revealed a reduction of swelling and leukocyte migration in the acute model for both the formulations of simvastatin (1% and 3%), while in chronic model simvastatin 1% decreased ear swelling and epidermal thickness, but simvastatin 3% increased both parameters. Conclusion: The results confirm the anti-inflammatory activity of simvastatin when applied topically in both acute and chronic models of skin inflammation. Besides, the formulation of simvastatin ointment 1% shows to be a very effective formulation for a chronic usage. [Copyright &y& Elsevier]

Abstract: The present study reports for the first time, the in vivo wound healing potential of Punica granatum L. peels. A 5% (w/w) methanolic extract based-ointment was formulated and evaluated for its wound healing in guinea pigs. The ointment was applied in vivo on the paravertebral area of twelve excised wounded models once a day for 10 consecutive days. The ointment significantly enhanced the wound contraction and the period of epithelialization as assessed by the mechanical (contraction rate, tensile strength), the biochemical (increasing of collagen, DNA and proteins synthesis) and the histopathological characteristics. Such investigation was encouraged by the efficiency of the methanolic extract as antimicrobial and antioxidant. Indeed, the extract showed antioxidant activity as strong as natural and synthetic compounds (Trolox, BHA, Quercetin). Furthermore, the extract exhibited significant antibacterial and antifungal activity against almost all tested bacteria: Pseudomonas aeruginosa ATCC 9027, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Klebsiella pneumoniae, Salmonella anatum, Salmonella typhimurium, Streptococcus pneumoniae, and fungi Candida albicans, Candida glabrata, Trichopyton rubrum and Aspergillus niger. The formulated ointment might well find use as skin repair agent without hazard to human health based on these results and on the fact that it has been well established that the extracts of pomegranate used in conditions similar to those applied by traditional medicine, showed no toxic effects. [Copyright &y& Elsevier]

Abstract: During archaeological excavations of the Castle of Middelburg (Belgium), a 16th century ceramic vessel containing a greasy substance was found. A wide range of chemical techniques was applied on what was presumed to be an ointment to reveal its nature and function. The organic fraction, constituting about 24wt.%, was analyzed by chromatography and mass spectrometry and consists of beeswax next to smaller amounts of a triglyceride lipid source. Infrared analyses indicated the presence of calcium carboxylate soaps. The inorganic ingredients represent about 30% of the total mass. While calcium, lead and iron were detected by elemental analysis, X-ray diffraction revealed calcium sulfate (gypsum) and lead sulfate as major minerals. Detailed study by X-ray photoelectron spectroscopy confirmed the presence of lead as a divalent species. Altogether, these results point to a medicinal formulation of a lead plaster, used for treating bruises, mixed with beeswax, which was added for easy application on the skin. It is further assumed that lead carboxylates, originally present in the sample, reacted with gypsum, resulting in the formation of calcium carboxylates and lead sulfate. Gypsum could have been added to whiten or to strengthen the plaster. Hence, the analyses confirm the presumed medicinal nature of the find and add it to the list of very rare finds of preserved historical ointments. [Copyright &y& Elsevier]

Abstract: The current USP National Formulary contains 65 Monographs for drug formulations containing neomycin. All 65 Monographs prescribe a bioassay for neomycin assay. This bioassay, based on cell culture, is labor intensive, has poor precision, and cannot be adapted for purity or identification. High-performance anion-exchange chromatography with integrated pulsed amperometric detection (HPAE-IPAD), a liquid chromatography technique, has been shown to be suitable for neomycin purity analysis and neomycin assay of an over-the-counter first aid cream (Hanko and Rohrer ). Here we propose that an HPAE-IPAD assay can replace the bioassay in the 65 neomycin-containing Monographs. We applied the HPAE-IPAD assay to four neomycin-containing drug products representing the four classes of formulations found in the 65 Monographs, liquid, solid, suspension, and cream. Each drug was analyzed with two chromatography systems, and on 3 separate days. For all products, HPAE-IPAD measurements were precise and accurate with respect to the label concentrations. There was also high accuracy for spike recovery of neomycin from the four drug products throughout 70–150% of the labeled concentration. These results suggest that an HPAE-IPAD assay would be an accurate assay for neomycin, and would be faster and more precise than the current bioassay. [Copyright &y& Elsevier]

Abstract: The purpose of this study was the development of an analytical methodology for the determination of neomycin in a complex pharmaceutical preparation. The simplified methodology consisted of a primary liquid–liquid extraction, employing a mixture of chloroform and water (1.25:1, v/v) and subsequent analysis by CE applying a capillary zone electrophoresis method with a 30cm (effective length), 50μm (internal diameter) polyacrylamide-coated silica capillary. The background electrolyte consisted of 35mM phosphate and 15mM acetate buffer set at pH 4.7, under normal polarity mode and direct UV detection at 200nm. The separation of the target analyte from the complex matrix was accomplished in less than 3min. The analytical method was successfully validated in order to verify its proper selectivity, linearity, accuracy and precision for the goal intended and its further implementation for the quantification of the active compound in the pharmaceutical speciality for quality control. [Copyright &y& Elsevier]

Abstract: Background: Thionamide antithyroid drugs (ATDs) have certain disadvantages and are associated with some adverse events (AEs). To overcome the problems associated with ATDs, a compound antithyroid ointment (CATO) containing methimazole (MMI) and hydrocortisone has been developed for use as a local thyroid treatment (LTT). Objective: The aim of this study was to assess the clinical effectiveness and tolerability of CATO LTT in patients with Graves disease (GD). Methods: This was a prospective, randomized, open-label, parallel-group clinical trial conducted at the Provincial Hospital Affiliated to Shandong University (Jinan, China). Patients with GD aged 19 to 65 years were randomized to receive either CATO LTT 0.3 g/d or oral MMI 37.5 mg/d (control group) treatment for 18 months, with a 4-year follow-up period. Hyperthyroid symptoms, thyroid function, granulocyte count, liver function, and AEs were assessed at baseline and every 2 weeks until serum thyroid hormone (TH) concentration normalized, at which point patients were assessed monthly. The primary efficacy end points were the duration of treatment required for serum TH concentration to normalize and the remission rate after completing the 18-month treatment regimen. Results: A total of 154 patients (133 women, 21 men; mean [SD] age, 39.6 [11.8] years; all Han Chinese) participated in the study; all patients completed the 18-month treatment period. Compared with the MMI group (n 76), the CATO- treated group (n 78) had a significantly shorter median (range) time to restoration of normal serum thyroid hormone concentration (43 [12–150] vs 22 [7–60] days; P < 0.001), a significantly lower rate of recurrence of hyperthyroidism (309/1520 [20.3%] vs 193/1368 [14.1%] person-time; P < 0.001), a significantly lower drug hypothyroidism rate (185/1520 [12.2%] vs 54/1368 [3.9%] person-time; P < 0.001), and a higher remission rate (year 1:46/69 [66.7%] vs 65/72 [90.3%] patients, P 0.001; year 2:40/69 [58.0%] vs 60/72 [83.3%] patients, P - 0.001; year 3:34/69 [49.3%] vs 57/72 [79.2%] patients, P < 0.001; and year 4:30/69 [43.5%] vs 55/72 [76.4%] patients, P < 0.001). Systemic AEs occurred in 6 patients (7.9%) in the MMI group (drug neutropenia, 2 patients [2.6%]; epistaxis, 1 [1.3%]; hepatopathy, 1 [1.3%]; and other systemic AEs, 2 [2.6%]), while no systemic AEs were observed/reported in the CATO group. Conclusion: This study suggests that CATO LTT was well tolerated and more effective than oral MMI treatment in controlling thyrotoxicosis and promoting remission of GD in these Han Chinese patients. [Copyright &y& Elsevier]

Abstract: A flow-injection chemiluminescence (CL) method coupled with solvent extraction for the determination of dexamethasone acetate (DA) in ointment was presented in this paper. It was based on the enhancing effect of the studied drug on CL emission of luminol–K3Fe(CN)6 system. This method has the advantages of simple sample treatment, cheap instrumentation and rapid detection. Under the optimum conditions, relative CL intensities were proportional to DA concentrations in the 0.044–4.4μgml−1 range. The limit of detection was 0.01μgml−1 (3σ) for DA. The method was applied to DA quantification in commercial DA ointment pharmaceutical and to human skin DA absorption analysis. Experiments were performed to evaluate the nature of DA enhanced luminol–K3Fe(CN)6 CL reaction. Based on the experimental results, it was suggested that in this CL system, DA was oxidized by K3Fe(CN)6 to form a medium product (DAox), DAox oxidized luminol with a faster kinetic step comparing with K3Fe(CN)6 oxidized luminol to an active form. As a result, DA speed the luminol CL reaction, and finally intensified the CL signal. [Copyright &y& Elsevier]

Abstract: A second order polynomial calibration model was developed and statistically validated for the direct and non-destructive quantitative analysis – without sample preparation – of the active pharmaceutical ingredient (API) salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy. The calibration curve was modeled by plotting the peak intensity of the vector normalized spectral band between 757 and 784cm−1 against the known salicylic acid concentrations in standards. At this band, no spectral interferences from the ointment vehiculum (white vaseline) are observed. For the validation of the polynomial model, its fit and its predictive properties were evaluated. The validated model was used for the quantification of 25 ointments, compounded by different retail pharmacists. The same standards and samples were used, both for development and validation of a regression model and for quantitative determination by HPLC – with sample preparation – as described for the related substances of salicylic acid in the Ph. Eur. IV. The quantification results obtained by the FT-Raman method corresponded with the HPLC results (p =0.22), provided that the particle size of salicylic acid in the standards is the same as in the analyzed samples. The non-destructive FT-Raman method is a reliable alternative for the destructive HPLC method, as it is faster and does not require sample pre-treatment procedures. [Copyright &y& Elsevier]

Abstract: A novel fast isocratic reversed-phase HPLC method for simultaneous determination of chlorhexidine and its degradation product p-chloroaniline was developed. Zorbax SB Phenyl column (75mm×4.6mm, 3.5μm) was used for the separation. Mobile phase composed of acetonitrile and buffer solution of 0.08M sodium phosphate monobasic containing 5ml of triethylamine (0.5%) and adjust with 85% phosphoric acid to pH 3.0 in ratio 35:65 (v/v) pumped isocratically at flow rate 0.6mlmin−1 was used. UV detection was performed at 239nm, the total analysis time was about 10min. The method is suitable for practical routine analysis of topical ointment in the quality control laboratory. [Copyright &y& Elsevier]

Abstract: Formulation containing neomycin and ghee was evaluated for wound-healing potential on different experimental models of wounds in rats. The rats were divided into six groups of group 1 as control, group 2 as treated with neomycin only, group 3 as treated only with ghee, group 4 treated with F-1 formulation containing ghee 40% and neomycin 0.5%, group 5 treated with F-2 formulation containing ghee 50% and neomycin 0.5% and group 6 treated with F-3 formulation containing ghee and ointment base in all two wound models, each group consisting of six rats. Wound contraction ability in excision wound model was measured at different time intervals and study was continued until wound is completely healed. Tensile strength was measured in 10-day-old incision wound and quantitative estimation of hydroxy proline content in the healed tissue was determined in 10-day-old excision wound. Histological studies were done on 10-day-old sections of regenerated tissue of incision wound. F-2 formulation containing ghee 50% and neomycin 0.5% showed statistically significant response, in terms of wound contracting ability, wound closure time, period of epithelization, tensile strength of the wound, regeneration of tissues at wound site when compared with the control group and these results were comparable to those of a reference neomycin ointment. [Copyright &y& Elsevier]

Abstract: Current definitions of lotions, gels, creams and ointments vary depending on literature source, market history or traditional use. This often leads to confusion when deciding which dosage form to prescribe and/or purchase. The existing classification of topical dosage forms needs to be re-examined to ensure that definitions for different dosage forms are based on consistent scientific principles and that dosage forms can be distinguished from one another. The purpose of this study is to obtain a scientifically based, systematic classification of dosage forms for topical drugs. A variety of prescription and over-the-counter topical products currently marketed as lotions, gels, creams, and ointments are evaluated using different techniques including rheology (viscosity and shear rate versus shear stress), loss on drying (LOD), specific gravity, surface tension, thermogravimetric analysis (TGA), water absorption, dilution properties, microscopic evaluation, transmittance of visible light, appearance and composition. Rheology is the most discriminating property separating creams and lotions. Water plus volatiles (as measured by LOD) and composition separate ointments and creams. Composition and thermal behavior separate gels from the other dosage forms. Based on these findings, new definitions and a decision tree are presented to assist in the determination of the appropriate nomenclature for a topical dosage form. [Copyright &y& Elsevier]

The in vitro release profiles and the bleeding phenomenon of Tacrolimus and propylene carbonate (PC) as a dispersing solvent for Tacrolimus drug substance in Tacrolimus ointment were investigated when changing concentrations of Tacrolimus and PC in the ointment were used, respectively. The bleeding test result indicated that Tacrolimus was in equilibrium between inside and outside of PC droplets in intact ointment base. A cumulative release amount of Tacrolimus from ointment, plotted against the square root of time, showed a straight line initially with a slope of q1 followed to change a slope to be q2 at a certain time, where the relation of these slopes being q1. The q1 values increased with the concentration of Tacrolimus but decreased with PC concentration in Tacrolimus ointment. And the q2 values increased with Tacrolimus concentration but were independent of PC concentration. These profiles indicated that there were two phases for Tacrolimus release from ointment, namely, first phase was related with the period during PC release and the second phase was related with the state of ointment after PC release. When the PC release was applied to the Higuchi’s release equation, the above slope q1 was found to be correlated to the parameter of A/φ0, where A was a parameter of release rate of PC and φ0 was an initial volume fraction of PC droplets. It should be indicated that more rapid release rate of PC rather than that of Tacrolimus resulted in the generation of amorphous phase of Tacrolimus outside of remaining PC droplets. During PC release, the slope q1 could be influenced by the thermodynamic activity of Tacrolimus dissolved in PC droplets. After PC release, it would be reasonable to speculate that the amorphous cluster of Tacrolimus with a constant thermodynamic activity would give constant q2 values regardless of PC contents in Tacrolimus ointment. [Copyright &y& Elsevier]

The quantitative aspects of a micellar electrokinetic chromatographic (MEKC) method for the determination of three preservatives (imidazolidinyl urea, methyl and propylparabens) in a pharmaceutical ointment are presented. Separation was carried out in a 31.2 cm long (21 cm to the detection window) × 50 μm i.d. fused silica capillary at an electric field of 960 V/cm and 25 °C. The electrolyte was 10 mM sodium dihydrogenophosphate containing 40 mM sodium dodecylsulfate (SDS) and adjusted to pH 6.1. Sample preparation consisted of a simple dispersion of the ointment in an internal standard solution (ethylparaben in the electrolyte). A 3.5 nl volume of the sample solution was introduced hydrodynamically into the capillary. The compounds detected at 200 nm were separated within 1.6 min. The method was validated with respect to specificity, linearity, accuracy, repeatability according to the International Conference on Harmonisation guidelines. Calibration curves were found to be linear for each compound (r2>0.999). Recovery studies performed by spiking an ointment placebo with the preservatives between 50 and 150% of their target concentration on 3 different days gave satisfactory results (mean recovery at each of the five concentrations ranging from 99.23 to 101.40%). The repeatability of sample preparation (n=6) was better than 2% for each of the preservatives. [Copyright &y& Elsevier]

[Display omitted] • When determining POL and CIN in their raw material states and dosage forms, the established spectrofluorimetric method was simple, specific, precise and accurate. • The method was successfully validated in terms of precision, accuracy, LOD and LOQ, selectivity, and linearity. • Compared to HPTLC, the proposed approach is less complex, involving many changes and no need for many steps. • The application of the existing technique for the quality control of both compounds in pharmaceutical dosage forms could be recommended for these benefits. For the treatment of internal and external hemorrhoids, policresulen (POL) and cinchocaine hydrochloride (CIN) are used in combination. Using a new, simple, fast, and economical first-derivative synchronous fluorescence spectroscopic process, both drugs were simultaneously determined and validated. At Δλ 60 nm and with a scanning rate of 600 nm/min, methanol was used as the solvent for both products. In the concentration ranges of 5.0–21.0 μg mL−1 and 0.5–6.0 μg mL−1 for POL and CIN, the amplitude-concentration plots were rectilinear. The detection limits were found to be 0.770 μg mL−1 and 0.118 μg mL−1 and the quantitation limits for POL and CIN were 2.541 μg mL−1 and 0.391 μg mL−1. To evaluate all compounds in synthetic mixtures and medicinal dosage types, the proposed method has been successfully applied. These findings were in line with the results obtained using high-performance thin layer chromatography, the comparison process. [ABSTRACT FROM AUTHOR]

Formulating new wound-healing ointments by natural compounds is the first research priority in the developing and developed countries. This study was intended to provide green formulation of Ag-NP ointment containing Citrus lemon leaf aqueous extract and examine its capability of healing cutaneous wounds and its antioxidant and cytotoxicity activities under in vitro and in vivo conditions. Different techniques, including UV–Vis and FT-IR spectroscopy, were used to characterize Ag-NPs. MTT assay was used to investigate cytotoxicity property of Ag-NPs. Antioxidant activity of Ag-NPs were examined by DPPH in the presence of butylated hydroxytoluene as positive control. Parameters of cutaneous wound healing were measured both histopathologically and biochemically. Clear peak at 429 nm shown by UV–Vis spectroscopy indicated formation of Ag-NPs. In FT-IR spectroscopy, presence of many antioxidant compounds provided an excellent condition to reduce silver in Ag-NPs. FE-SEM and TEM images showed spherical Ag-NPs with an average size of 25.1 nm. The synthesized silver nanoparticles had excellent cell viability on the HUVECs line and indicated this method was nontoxic. Application of Ag-NP ointment improved wound healing parameters significantly (P ≤ 0.01). Ag-NPs reduced wound areas, total cells, neutrophils and lymphocytes significantly (P ≤ 0.01) and increased wound contracture, vessels, hexosamines, hydroxyl proline, hexuronic acid, fibrocytes, fibroblasts and fibrocyte/ fibroblast ratios significantly (P ≤ 0.01). Once our results are verified by clinically experimental studies, Ag-NP ointment can be used as a modern one to treat several types of wounds, especially cutaneous ones, in humans. [ABSTRACT FROM AUTHOR]

• Complex of silver(I) with metronidazole shows a potential to treat ocular rosacea. • Metronidazole/silver ions drops/ointment do not cause severe side effects. • Different forms of medicine are simple to prepare. Metronidazole with well-soluble silver nitrate forms a complex with potent activity (synergism) against bacterial strains and fungi with simultaneous lower side effect than in the case of the two agents administered separately. This study aimed to establish effectiveness in the treatment of ocular rosacea with new formulation of drops and ointment with silver(I) complex of metronidazole. Three patients suffering from serious ophthalmic complications of acne rosacea were treated with drops and ointments applied 3 times a day for 3 months. The uncorrected visual acuity testing (UCVA), pachymetry as well as subjective and objective tear film assessment were evaluated. In all patients, we have improved UCVA as well as objective and subjective evaluation of the tear film parameters. No significant differences in corneal thickness were observed. Well soluble silver(I) complex of metronidazole might be an alternative method in ophthalmic complications of acne rosacea treatment. [ABSTRACT FROM AUTHOR]

Excipients from different sources may lead to significant differences in the performance of drug products, posing challenges in product quality control. A previous report showed that the drug release rates from ophthalmic ointments were affected by source variation of white petrolatum. To understand the physicochemical properties including the microstructure of white petrolatum and the impact of this on the performance of finished products, the following were investigated: rheological properties, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), as well as structural characteristics (polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS)). The rheological parameters may be indicative of the drug release rate of the finished ophthalmic ointments when using a process involving hot-melting with immediate cooling. The white petrolatum from the four different sources also showed different thermal behavior. According to SAXS and WAXS, all of the petrolatum showed semi-crystalline behavior with different extents of crystallinity (from 9.5% to 16.9%). The crystalline domains of the petrolatum are ordered in an orthorhombic structure forming lamellar sheets with a periodicity from 9.1 nm to 9.9 nm. An in-depth understanding of the semi-crystalline structure was obtained and it provided valuable information for formulation optimization and characterization of petrolatum-based products. [ABSTRACT FROM AUTHOR]

The use of herbal medicines is increasing in developed countries as alternative and/or supportive therapy to conventional health care medicines. Malva neglecta Wallr. (Family: Malvaceae) has been reported as wound healing remedy in traditional medicines, however no experimental data is available on its wound healing potentials. The aim of this study was to explore phytochemistry and validate wound healing potentials of the plant using animal models. M. neglecta crude methanolic extract (Mn.Cme) was chemically characterized using HPLC-DAD and GCMS analysis. Acute dermal toxicity was determined in albino rats following Organization of Economic Co-operation and Development (OECD) 402 established standards. Wound healing potentials were evaluated in rats using excision wound model. Wounds (177 mm2) were made by an excision on the skin of rats which were placed individually in cages. Mn.Cme was formulated in ointment form and was applied topically onto the wound area once daily for 14 days. The wound area was measured with translucent paper and thereafter estimated on a 1 mm2 graph sheet every 3rd day until epithelialization and complete wound closure was recorded. Wound contraction was calculated as a percentage of the original wound size. Antioxidant potentials were also evaluated via FRAP, DPPH and H 2 O 2 free radicals scavenging assays. HPLC-DAD analysis revealed 25 phenolic compounds with higher amounts of hydrotyrosol (109.3 mg/g), coumaroylhexoside (97.4 mg/g), kaempferol-3-(p-coumaroyldiglucoside)-7-glucoside (37.2 mg/g), quercetin-3- O -rutinoside (31.5 mg/g) and epicatechin-3- O -(4- O -methyl)-gallate (31.3 mg/g). In GC-MS analysis, oleic acid (19.67%), taurine (17.60%), ethylene dimercaptan (14.67%), isoeugenol (14.61%), patchoulane (10.36%), methyl 12-methyltetradecanoate (8.47%) and isopropyl myristate (7.02%) were highly abundant compounds. No sign of toxicity was observed in the acute dermal toxicity test. Our test sample (Mn.Cme) exhibited considerable wound healing tendency at all doses (1 g, 1.5 g, 2 g per 10 g of ointment base) with reduced epithelialization period in a dose–related manner. Absolute healing was observed after application of 2 g of Mn.Cme ointment. Further, Mn.Cme exhibited considerable anti-radical potential in all assays. It may be concluded that M. neglecta possess very potent secondary metabolites which are previously reported for wound healing potentials. The plant has considerable antioxidant and wound healing properties and thus warrant further studies to uncover the molecular mechanism its wound healing potentials. Image 1 [ABSTRACT FROM AUTHOR]

Proanthocyanidins (PCs), a component of grape seed extract (GSE), have recently being used for the treatment of wounds. However, poor absorption, poor stability and rapid elimination from the systemic circulation limit its acceptance. In addressing these problems, we herein report the development of PCs based nanoformulations (PCs/SOLU) for the first time based on 1% GSE and assessed its wound healing potential in - vivo on the wistar rats. GSE and PCs/SOLU nanodispersions 1% were prepared by incorporating them into the ointment base via uniform mixing to form ointment which could be easily applied topically to wounds. The antibacterial activity of PCs/SOLU against gram positive and gram-negative bacteria strains proved that the cell membranes became more permeable with disrupted cell structure. While carrageenan and histamine induced rat paw edema analyses show there was no inflammatory signs in animals treated with 1 wt% of PCs/SOLU nanodispersion. Excision wound measuring about 3 cm in depth was created on the wistar rats. The ointment was applied topically on the wounded site and the wound contraction was measured daily. Grape seed extract (GSE) ointment, ointment base and povidone‑iodine (Povi-Iod) ointment of about 1% was used as the control, positive and negative standards. PCs/SOLU nanodispersion heals the wound by mobilising the fibroblasts in the wound site and inhibits the inflammatory response through decreased expression of monocyte. The macroscopical, immunological and histopathological assessments revealed that PCs/SOLU nanodispersion ointment usage improves the cell adhesion and proliferation. Mechanism of wound healing activity of PCs/SOLU Unlabelled Image • Proanthocyanidins based nanoformulations was assessed for wound healing potential. • Antibacterial activity shows rupture of cell and damages the genetic material. • Carrageenan and histamine induced edema analyses showed no inflammatory signs. • Nanodispersion heals the wound by mobilising the fibroblasts in the wound site. • Histopathological assay revealed that nanodispersion improves cell proliferation. [ABSTRACT FROM AUTHOR]

Background: Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease.Objective: To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302).Methods: Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed.Results: During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs.Limitations: Long-term efficacy was not analyzed.Conclusion: Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD. [ABSTRACT FROM AUTHOR]