The Efficacy and Biopharmaceutical Properties of a Fixed-Dose Combination of Disulfiram and Benzyl Benzoate.

Scabies and hair lice are parasitic diseases that affect human skin and hair, respectively. The incidence and resistances of these infections are increasing. Tenutex® (disulfiram and benzyl benzoate emulsion) is an alternative to standard insecticides to avoid resistances. The aim of the work is to evaluate the transdermal absorption and the in vitro efficacy against scabies and hair lice after different exposition times. Dermatomed human skin was used to assess the dermal absorption using a validated High Performance Liquid Chromatography (HPLC) method. HEK001 keratinocytes were used to evaluate the cytotoxicity of benzyl benzoate. Only benzyl benzoate was able to cross the skin, but it did not show cytotoxicity at any of the tested concentrations. The product efficacy was tested on Psoroptes ovis after direct contact and after administration on sheep skin explants at different contact times. Permethrin/malathion-resistant strains of Pediculus humanis capitis adults and eggs were directly exposed to Tenutex, and the vitality and hatchability, respectively, were evaluated. The anti-scabies study demonstrated that exposure for 6 or 24 h completely eradicated the parasite. The pediculicidal activity of Tenutex exhibited superior efficacy than standard treatment on resistant lice. The positive results obtained suggest that Tenutex® is a good treatment option, especially in drug resistance situations.

Pilot Equivalence Study Comparing Different Batches of Topical 0.025% Capsaicin Emulsion: Product Microstructure, Release, and Permeation Evaluation.

The European Medical Agency (EMA) has issued a draft guideline on the quality and equivalence of topical products. The equivalence for complex semisolid formulations involves several steps: the same quantitative content, the same microstructure, the same release, and permeation profile. In this paper, several batches of a low strength topical product, which we used as a reference/comparator product, were evaluated according to the recommendations of the EMA draft guideline. The batches were 0.025% capsaicin emulsions from the same manufacturer that were evaluated in terms of droplet size, X-ray diffraction patterns, rheology, release, and permeation profile. The generated data revealed a large batch-to-batch variability, and if the EMA guideline was applied, these batches would not be considered equivalent, although they were produced by the same manufacturer. The result of this work illustrates the difficulties in obtaining equivalence according to the current draft guidelines. It also highlights that the equivalence guidelines should consider the variability of the comparator product, and in our opinion, the guidelines should allow for claiming equivalence by comparing the limits in the variability of the data generated for the comparator product with the limits in the variability of the data generated for the intended equivalence product.

Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study.

BACKGROUND: Penicillin G, the current standard treatment for syphilis, has important drawbacks, but virtually no preclinical or clinical studies have been performed to identify viable alternatives. We tested, both in vitro and in vivo, three marketed antibiotics with adequate pharmacological properties to treat syphilis. METHODS: We used an in vitro culturing system of T. pallidum to perform drug susceptibility testing and applied quantitative PCR targeting the tp0574 gene to measure bacterial growth. To confirm in vivo efficacy, fifteen rabbits were infected intradermally with T. pallidum at eight sites each and randomly allocated to an experimental treatment (linezolid, moxifloxacin, clofazimine) or a control arm (benzathine penicillin G [BPG], untreated). The primary outcome was treatment efficacy defined as the time to lesion healing measured from the date of treatment start. Secondary outcomes were absence of treponemes or treponemal mRNA in injection sites, absence of seroconversion, and cerebrospinal fluid (CSF) abnormalities and negative rabbit infectivity tests (RIT). FINDINGS: Linezolid showed in vitro bactericidal activity at concentrations of 0.5 µg/mL or higher. When administered orally to experimentally infected rabbits, it induced healing of early lesions at a time similar to BPG (hazard ratio 3.84; 95% CI 2.05-7.17; p < 0.0001 compared to untreated controls). In linezolid-treated animals, dark-field microscopy and qPCR assessment showed no presence of treponemes after day 3 post-treatment start, serologic test did not convert to positive, CSF had no abnormalities, and RIT was negative. Moxifloxacin and clofazimine failed to inhibit bacterial growth in vitro and could not cure the infection in the rabbit model. INTERPRETATION: Linezolid, a low-cost oxazolidinone, has in vitro and in vivo activity against T. pallidum, with efficacy similar to BPG in treating treponemal lesions in the animal model. Our findings warrant further research to assess the efficacy of linezolid as an alternative to penicillin G to treat syphilis in human clinical trials. FUNDING: European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 850450).

Amoxicillin and Clarithromycin Mucoadhesive Delivery System for Helicobacter pylori Infection in a Mouse Model: Characterization, Pharmacokinetics, and Efficacy.

Helicobacter pylori is the main pathogen responsible for gastric ulcers and a predisposing factor of stomach cancer. Although current treatment is usually successful, it requires high doses and frequent administration. An innovative mucoadhesive system (Mucolast®) loaded with amoxicillin and clarithromycin is proposed to improve the efficacy of treatment against H. pylori. The drug product was optimized based on its viscoelastic properties to obtain long-term stability of the vehicle. The drug release mechanisms were different for both antibiotics based on their solubilization status. A systemic and stomach pharmacokinetic profile was obtained after three different doses were administered to mice, obtaining similar systemic exposure levels but an increase in drug concentration in the stomach. The efficacy results in mice infected with H. pylori also demonstrated the superiority of the antibiotics when administered in Mucolast®, as shown by the bacterial count in stomach tissue and under histopathological and biochemical evaluation. The proposed treatment was efficacious and safe and is presented as a realistic alternative to current treatment options to improve patient compliance and to reduce bacterial resistance.

A topical microemulsion for the prevention of allergic rhinitis symptoms: results of a randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial (Nares study).

BACKGROUND: Since barrier protection measures to avoid contact with allergens are being increasingly developed, we assessed the clinical efficacy and tolerability of a topical nasal microemulsion made of glycerol esters in patients with allergic rhinitis. METHODS: Randomized, controlled, double-blind, parallel group, multicentre, multinational clinical trial in which adult patients with allergic rhinitis or rhinoconjunctivitis due to sensitization to birch, grass or olive tree pollens received treatment with topical microemulsion or placebo during the pollen seasons. Efficacy variables included scores in the mini-RQLQ questionnaire, number and severity of nasal, ocular and lung signs and symptoms, need for symptomatic medications and patients' satisfaction with treatment. Adverse events were also recorded. RESULTS: Demographic characteristics were homogeneous between groups and mini-RQLQ scores did not differ significantly at baseline (visit 1). From symptoms recorded in the diary cards, the ME group showed statistically significant better scores for nasal congestion (0.72 vs. 1.01; p = 0.017) and mean total nasal symptoms (0.7 vs. 0.9; p = 0.045). At visit 2 (pollen season), lower values were observed in the mini-RQLQ in the ME group, although there were no statistically significant differences between groups in both full analysis set (FAS) and patients completing treatment (PPS) populations. The results obtained in the nasal symptoms domain of the mini-RQLQ at visit 2 showed the highest difference (-0.43; 95% CI: -0.88 to 0.02) for the ME group in the FAS population. The topical microemulsion was safe and well tolerated and no major discomforts were observed. Satisfaction rating with the treatment was similar between the groups. CONCLUSIONS: The topical application of the microemulsion is a feasible and safe therapy in the prevention of allergic symptoms, particularly nasal congestion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01478425.