Comparative Evaluation of Residual Antibacterial Substantivity of Chlorhexidine, MTAD and Chitosan Against Enterococcus Faecalis in Human Root Dentin - An In vitro Study.

Introduction: Complex anatomy of the root canal system results in incomplete debridement with mechanical instrumentation, leaving some areas or root canal walls untouched. There comes the significance of endodontic irrigants with residual antibacterial substantivity which prolongs the post-antibiotic effect, thereby improving the success and predictability of endodontic treatment. Aim: To comparatively evaluate the residual antibacterial substantivity of 2% chlorhexidine, Biopure MTAD and 2% chitosan against Enterococcus faecalis at intervals of 1, 14 and 28 days. Materials and Methods: Seventy-five therapeutically extracted permanent single rooted mandibular premolars teeth were selected. Dentin blocks of 4 mm thickness were prepared and enlarged to 1.6 mm. The autoclaved blocks were inoculated with 24-hour colonies of pure cultures of E. faecalis for 14 days. After the contamination period, canals of each dentin block were irrigated with 5 ml of sterile saline and dried with sterile paper points. A total of 75 dentin blocks were randomly divided into five groups as follows: Group A (21 specimens): 2% chlorhexidine, Group B (21 specimens): Biopure MTAD, Group C (21 specimens): 2% chitosan, Group D (6 specimens): positive control (infected dentin tubes) and Group E (six specimens): negative control (sterile dentin tubes). Then, the lumens of dentin blocks were irrigated with the respective irrigants for 10 mins and were dried using sterile paper points. The specimens were then incubated at 37°C for 28 days to maintain humidity. At experimental intervals of 1, 14 and 28 days, dentin shavings were removed from the canals of respective groups by circumferential filing with sterile no. 35 Hedstrom files. The powdered dentin samples obtained with each dentin block were observed for colony forming units (CFUs) using a Digital Colony counter and were expressed as CFUs/mL. Result: All the irrigants in the study showed a significant decrease in CFUs from day 1 to day 28 indicating that they have residual antibacterial substantivity against E. faecalis. Group B (Biopure MTAD) showed significantly least mean CFUs compared to Group A (2% CHX) and Group C (2% chitosan) against E. faecalis at B1(day 1), B2(day 14) and B3(day 28). Group A (2% CHX) showed significantly higher mean CFUs than Group C (2% chitosan) at A1(day 1). Group C (2% chitosan) showed significantly higher mean CFUs compared to Group A (2% CHX) at C2(day 14) and C3 (day 28). Conclusion: MTAD showed statistically higher residual antibacterial substantivity against E. faecalis at experimental periods of 1, 14 and 28 days. The residual antibacterial effect of 2% chitosan was better compared to 2% CHX at day 1. The residual antimicrobial substantivity of 2% CHX was higher compared to 2% chitosan at intervals of 14 and 28 days.

Development of a film-forming oleogel with increased substantivity for the treatment of psoriasis.

The aim of this work was the development of a film-forming formulation (FFF) for the topical treatment of psoriasis that shows an increased substantivity compared to conventional semi-solid dosage forms. The developed formulation is an oleogel. It is based on a combination of castor oil and medium chain triglycerides, and the oil-soluble film former MP-30 (Croda GmbH, Nettetal, Germany), a polyamide that upon mixing with a polar oil entraps the oil und thus substantially increases the viscosity of the formulation up to a semisolid state. Betamethasone dipropionate (BDP) and calcipotriole (CA) were used as active pharmaceutical ingredients (APIs). Oleogels of different compositions were evaluated regarding substantivity, rheological properties, ex-vivo penetration into the skin and ex-vivo permeation through the skin. Marketed products were used as controls. It was found that the amount of betamethasone dipropionate penetrating and permeating into and through the skin from the film-forming formulation is at an intermediate value compared to the marketed products. The substantivity of the developed formulation is described by an amount of 57.7 % formulation that remains on the skin surface and is thus significantly higher compared to the marketed products. In the film forming formulation, the proportion of API penetrating the skin remains the same when the skin repetitively brought in contact with a piece of textile during the penetration experiment. In contrast with the in-market formulations tested, this proportion was reduced by up to 97 %. As a result, the developed formulations can lead to an increased patient compliance.

Formulation and assessment of biological properties of garcinia indica fruit extract mouthrinse as an adjunct to oral hygiene regimen: an in vitro analysis

Abstract The prevalence of gingivitis is substantial within the general population, necessitating rigorous oral hygiene maintenance. Objective This study assessed a Garcinia indica (GI) fruit extract-based mouthrinse, comparing it to a 0.1% turmeric mouthrinse and a 0.2% Chlorhexidine (CHX) mouthrinse. The evaluation encompassed substantivity, staining potential, antimicrobial efficacy and cytocompatibility. Methodology The study employed 182 tooth sections. For antimicrobial analysis, 64 extracted human teeth coated with a polymicrobial biofilm were divided into four groups, each receiving an experimental mouthrinse or serving as a control group with distilled water. Microbial reduction was assessed through colony forming units (CFU). Substantivity was evaluated on 54 human tooth sections using a UV spectrophotometer, while staining potential was examined on 64 tooth sections. Cytocompatibility was tested using colorimetric assay to determine non-toxic levels of 0.2% GI fruit extract, 0.1% Turmeric, and 0.2% CHX. Results Data were analysed with one-way ANOVA (α=0.05). Cell viability was highly significant (p<0.001) in the 0.2% GI group (64.1±0.29) compared to 0.1% Turmeric (40.2±0.34) and 0.2% CHX (10.95±1.40). For antimicrobial activity, both 0.2% GI (20.18±4.81) and 0.2% CHX (28.22±5.41) exhibited no significant difference (P>0.05) at end of 12 hours. However, 0.1% Turmeric showed minimal CFU reduction (P<0.001). Substantivity results at 360 minutes indicated statistically significant higher mean release rate in 0.1%Turmeric (12.47±5.84 ) when compared to 0.2% GI (5.02±3.04) and 0.2% CHX (4.13±2.25) (p<0.001). The overall discoloration changes (∆E) were more prominent in the 0.2% CHX group (18.65±8.3) compared to 0.2% GI (7.61±2.4) and 0.1% Turmeric (7.32±4.9) (P<0.001). Conclusion This study supports 0.2% GI and 0.1% Turmeric mouth rinses as potential natural alternatives to chemical mouth rinses. These findings highlight viability of these natural supplements in oral healthcare.

Mucoadhesive Pharmacology: Latest Clinical Technology in Antiseptic Gels.

Chlorhexidine (CHX) is one of the most widely used antiseptics in the oral cavity due to its high antimicrobial potential. However, many authors have stated that the effect of CHX in nonsurgical periodontal therapy is hampered by its rapid elimination from the oral environment. The aim of this study was to determine the antibacterial efficacy of a new compound of chlorhexidine 0.20% + cymenol (CYM) 0.10% on a multispecies biofilm. For this, an in vitro study was designed using a multispecies biofilm model of Streptococcus mutans, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. Quantification of the microbial viability of the biofilm was performed using 5-cyano-2,3-ditolyl tetrazolium-chloride (CTC) to calculate the percentage of survival, and the biofilms were observed using a a confocal laser scanning microscopy (CLSM). It was observed that the bactericidal activity of the CHX + cymenol bioadhesive gel was superior to that of the CHX bioadhesive gel, in addition to higher penetrability into the biofilm. Therefore, there was greater elimination of bacterial biofilm with the new compound of chlorhexidine 0.2% plus cymenol 0.1% in a bioadhesive gel form compared to the formulation with only chlorhexidine 0.2% in a bioadhesive gel form.

Substantivity of mouth-rinse formulations containing cetylpyridinium chloride and O-cymen-5-ol: a randomized-crossover trial.

BACKGROUND: The efficacy of mouth-rinses strongly depends upon their substantivity. The use of natural and non-toxic products that avoid secondary effects is gaining interest in preventive dentistry. The purpose of this study was to evaluate the substantivity of two formulations of mouth-washing solutions based on cetylpyridinium (CPC) and O-cymen-5-ol. METHODS: This was a randomized, double-blind, crossover trial conducted at the Faculty of Medicine and Health Sciences of the University of Barcelona. Bacterial re-colonization was followed by live/dead (SYTOTM9 + propidium iodide) bacterial staining and measured by confocal laser scanning microscopy and fluorometry. Unstimulated saliva samples were collected from 16 healthy individuals at baseline saliva and then, at 15 min, 30 min and 1, 2, 3, and 4 h after the following mouth-rinses: (i) a single, 1-min mouth-rinse with 15 ml of placebo (negative control); (ii) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) ; (iii) a single, 1-min mouth-rinse with 15 ml of O-cymen-5-ol (0.09%); (iv) a single, 1-min mouth-rinse with 15 ml of CPC (0.05%) + O-cymen-5-ol (0.09%). RESULTS: Proportion of dead bacteria was significantly higher for all mouthrinses during the first 15 min compared to baseline (CPC = 48.0 ± 13.9; 95% CI 40.98-56.99; p < 0.001, O-cymen-5-ol = 79.8 ± 21.0; 95% CI 67.71-91.90; p < 0.05, CPC + O-cymen-5-ol = 49.4 ± 14; 95% CI 40.98-56.99; p < 0.001 by fluorometry and 54.8 ± 23.0; 95% CI 41.50-68.06; p < 0.001, 76.3 ± 17.1; 95% CI 66.36-86.14; p < 0.001, 47.4 ± 11.9; 95% CI 40.49-54.30; p < 0.001 by confocal laser scanning microscopy, respectively). Nevertheless, after 4 h, CPC + O-cymen-5-ol was the only one that obtained significant values as measured by the two quantification methods used (80.3 ± 22.8; 95% CI 67.15-93.50; p < 0.05 and 81.4 ± 13.8; 95% CI 73.45-89.43; p < 0.05). The combined use of CPC + O-cymen-5-ol increased the substantivity of the mouthrinse with respect to mouthrinses prepared with either of the two active products alone. CONCLUSION: The synergistic interaction of CPC and O-cymen-5-ol prolongs their substantivity. The resulting formulation may be as effective as other antimicrobials, such as triclosan or chlorhexidine, but without their undesirable secondary effects. Thus, mouthrinsing products based on Combinations of CPC and O-cymen-5-ol may replace in the near future Triclosan and Chlorhexidine-based mouthrinses.

Simultaneous Physico-Mechanical and In Vivo Assessment towards Factual Skin Performance Profile of Topical Polymeric Film-Forming Systems.

Topical film-forming systems (FFS) change drastically after solvent displacement, therefore indicating their skin metamorphosis/transformation as a property of special regulatory and research interest. This paper deals with the lack of suitable characterization techniques, suggesting a set of methods able to provide a comprehensive notion of FFS skin performance. After screening the physico-chemical, mechanical and sensory properties of FFS and resulting films, an elaborate three-phase in vivo study was performed, covering skin irritation, friction and substantivity. Upon removal of 24-hour occlusion, no significant change in erythema index was observed, while the film-former type (cellulose ether, acrylate and/or vinyl polymer) affected transepidermal water loss (TEWL); hydrophobic methacrylate copolymer-based samples decreased TEWL by 40-50%, suggesting a semi-occlusive effect. Although both the tribological parameters related to the friction coefficient and the friction curve's plateau provided valuable data, their analysis indicated the importance of the moment the plateau is reached as the onset of the secondary formulation, while the tertiary state is still best described by the completion of the film's drying time. The final part of the in vivo study proved the high in-use substantivity of all samples but confirmed the optimal 4:1 ratio of hydrophobic cationic and hydrophilic polymers, as indicated during early physico-mechanical screening.

Antibacterial Action, Substantivity and Anti-plaque Effect of Different Toothpaste Slurries - A Randomised Controlled Trial.

PURPOSE: This single-center, clinically controlled, double-blinded, randomised, crossover study aimed to evaluate and compare the antibacterial effect, substantivity and patients' acceptance of three toothpaste slurries after a single application on established biofilms observed for 24 h. MATERIALS AND METHODS: Twenty-four participants started a test cycle after refraining from oral hygiene for 48 h, with a baseline plaque sample measuring biofilm vitality (in %; VF0) using vital fluorescence (VF). They were instructed to rinse for 1 min with either an amine fluoride, stannous chloride (ASC), an herbal (SBC) or a sodium fluoride (SFL) toothpaste prepared as slurries. Every two hours up to 12 and after 24 h, plaque samples were harvested (VF2-VF24%). Plaque-covered areas (PA in %) were evaluated after 24 h using digital photographs. Patients' acceptance was determined by visual analogue scale (VAS) questionnaire. RESULTS: All participants (16 women, 8 men; 27.5 ± 7.9 years) completed all cycles. Two hours after application (VF2), all toothpastes showed a statistically significant reduction in bacterial vitality (p < 0.05), maintained up to 12 h. ASC revealed statistically significantly lower vitality values compared to SBC at VF2, VF4, VF8, VF12 and VF24, and at VF4, VF12 and VF24 compared to SFL (p < 0.05), while SBC and SFL did not differ statistically significantly at any time point. The preferred toothpastes were SFL (18/24 participants) and ASC (15/24 participants). CONCLUSIONS: All toothpastes showed statistically significant anti-plaque effects on established plaque biofilm and a substantivity up to 24 h compared to their baseline, while ASC still presented a statistically significant effect after 12 and 24 h compared to SBC and SFL.

First insights into chlorhexidine retention in the oral cavity after application of different regimens.

OBJECTIVES: This in situ study aimed to determine and compare the chlorhexidine (CHX) retention in the oral cavity after the application of different CHX pharmaceutical regimens. METHODS: Five volunteers used different CHX treatment regimens including mouth rinses, dental spray and toothpaste gel. After the application of the different CHX regimens, 2-µl samples were taken from saliva and buccal mucosa pellicle as well as the dental pellicle samples formed on standardized enamel surfaces. Sample collection was conducted at six time points within 12 h. Retention of CHX was measured using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: CHX retention values in the oral mucosa pellicle were significantly higher than those in saliva. CHX remained in the mucosal pellicle at microgrammes per millilitre levels for 12 h after mouth rinsing, 10 h after spray application and 2 h after using the toothpaste. CHX was detected in the dental pellicle for at least 12 h after application of mouth rinsing and spray. Retention of CHX after mouth rinsing or spray application was significantly higher than the retention after using toothpaste. CONCLUSIONS: Oral mucosa was the favourable site for CHX retention. Higher mouth rinse concentration and longer rinsing time produced a slight increase in CHX retention. CHX spray provided considerable retention values, whereas toothpaste gel delivered the lowest retention after application. MALDI-TOF was a sensitive method with excellent limits of quantification for CHX detection.

In vitro skin model for characterization of sunscreen substantivity upon perspiration.

OBJECTIVE: The resistance of sunscreens to the loss of ultraviolet (UV) protection upon perspiration is important for their practical efficacy. However, this topic is largely overlooked in evaluations of sunscreen substantivity due to the relatively few well-established protocols compared to those for water resistance and mechanical wear. METHODS: In an attempt to achieve a better fundamental understanding of sunscreen behaviour in response to sweat exposure, we have developed a perspiring skin simulator, containing a substrate surface that mimics sweating human skin. Using this perspiring skin simulator, we evaluated sunscreen performance upon perspiration by in vitro sun protection factor (SPF) measurements, optical microscopy, ultraviolet (UV) reflectance imaging and coherent anti-Stokes Raman scattering (CARS) microscopy. RESULTS AND CONCLUSION: Results indicated that perspiration reduced sunscreen efficiency through two mechanisms, namely sunscreen wash-off (impairing the film thickness) and sunscreen redistribution (impairing the film uniformity). Further, we investigated how the sweat rate affected these mechanisms and how sunscreen application dose influenced UV protection upon perspiration. As expected, higher sweat rates led to a large loss of UV protection, while a larger application dose led to larger amounts of sunscreen being washed-off and redistributed but also provided higher UV protection before and after sweating.

OBJECTIF: La résistance des écrans solaires à la perte de protection contre les ultraviolets (UV) à cause de la transpiration est importante quant à leur efficacité pratique. Cependant, ce point est généralement négligé dans les évaluations de la substantivité des écrans solaires en raison du nombre relativement faible de protocoles bien établis, en comparaison avec ceux pour la résistance à l'eau et l'usure mécanique. MÉTHODES: Dans le but de parvenir à une meilleure compréhension fondamentale du comportement des écrans solaires en cas d'exposition à la sueur, nous avons développé un simulateur de peau transpirante, dont la surface de substrat imite la transpiration de la peau humaine. À l'aide de ce simulateur, nous avons évalué les performances des écrans solaires lors de la transpiration par des mesures in vitro du facteur de protection solaire (FPS), par microscopie optique, par imagerie de la réflectance ultraviolette (UV) et par microscopie cohérente de diffusion Raman anti-Stokes (coherent anti-Stokes Raman scattering, CARS). RÉSULTATS ET CONCLUSION: Les résultats ont montré que la transpiration réduisait l'efficacité de l'écran solaire en raison de deux mécanismes, à savoir le lavage de l'écran solaire (altération de l'épaisseur du film) et la redistribution de l'écran solaire (altération de l'uniformité du film). De plus, nous avons étudié comment le taux de transpiration affectait ces mécanismes et comment la dose d'application d'écran solaire influençait la protection UV en cas de transpiration. Comme l'on pouvait s'y attendre, des taux de sueur plus élevés ont entraîné une perte importante de protection contre les UV, tandis qu'une dose d'application plus importante a conduit à des quantités plus importantes d'écran solaire lavé et redistribué, mais a également fourni une protection contre les UV plus élevée avant et après la transpiration.

Brief descriptions of the principles of prominent methods used to study the penetration of materials into human hair and a review of examples of their use.

Consumers are attracted to the latest fashion trends and different looks. This drives the search for novel hair treatments. Some chemicals present in hair treatment products can penetrate the hair shaft. These materials can either nourish or injure the hair cortex. Different techniques have been used to investigate the mechanism of molecule penetration and the conditions under which penetration occurs. This article reviews the techniques applied for this purpose. Various microscopy techniques are used to capture clear and colourful images to determine the diffusion pathways and the exact location of the molecules under study. However, the laborious sample preparation often leads to sample destruction since cross-sectioning is often required. While various other techniques have been successfully used for investigating the penetration methods, most of these require different amounts of work to be put in for sample preparation and instrumentation. Several spectroscopic techniques have been used to study the penetration of the molecules because of the high levels of accuracy and the quick response time of these techniques. Moreover, the samples are not damaged during the investigation.

Les consommateurs sont attirés par les dernières tendances et les différents styles de la mode. Cela stimule la recherche pour de nouveaux traitements capillaires. Certains produits chimiques présents dans les produits de soins capillaires peuvent pénétrer la tige du cheveu. Ils peuvent tantôt nourrir, tantôt endommager le cortex pileux. Différentes techniques ont été utilisées pour étudier le mécanisme de pénétration des molécules et les conditions dans lesquelles cette pénétration a lieu. Cet article examine les techniques appliquées à cette fin. Diverses techniques de microscopie sont mises en œuvre pour capturer des images claires et colorées afin de déterminer les voies de diffusion et la localisation exacte des molécules à l'étude. Cependant, la préparation laborieuse des échantillons conduit fréquemment à la destruction des échantillons, car une coupe transversale est souvent exigée. Si plusieurs autres techniques ont été utilisées avec succès pour étudier les méthodes de pénétration, la plupart d'entre elles nécessitent différents niveaux d'activité à mettre en œuvre pour la préparation des échantillons et l'instrumentation. Plusieurs techniques spectroscopiques ont été utilisées pour étudier la pénétration des molécules en raison de leurs niveaux élevés de précision et de leur délai de réponse rapide. De plus, les échantillons ne sont pas endommagés pendant l'investigation.

Comparative evaluation of substantivity of two biguanides - 0.2% polyhexanide and 2% chlorhexidine on human dentin.

BACKGROUND: Substantivity is one of the desirable characteristics of root canal irrigants. Among conventional endodontic irrigants, only chlorhexidine (CHX) is known to exert significant substantivity on root canal dentin. This study explored the substantivity activity of a polymeric biguanide-poly hexamethylene biguanide (PHMB). AIM: The aim of this study was to determine the substantivity of a polymeric biguanide - 0.2% PHMB and compare it with that of 2% CHX. MATERIALS AND METHODS: To evaluate and compare the substantivity of 0.2% PHMB and 2% CHX on root canal dentin, dentin disks were prepared and substantivity after 1 h, 24 h, 7 days and 21 days was measured using spectrophotometry. STATISTICAL ANALYSIS USED: The data so obtained were analyzed, and the intergroup comparison was made using unpaired t-test. RESULTS: The results of this study indicated that 0.2%. PHMB exerts significantly greater substantivity than 2% CHX on human dentin. CONCLUSION: Within the limitations, this study supports the use of 0.2% polyhexanide as an endodontic irrigant based on its property of substantivity.

Determination of chlorhexidine retention in different oral sites using matrix-assisted laser desorption/ionization-time of flight mass spectrometry.

OBJECTIVE: The aim of this study was to determine chlorhexidine retention in different oral sites after a one-time 30 s mouth rinsing. DESIGN: Five volunteers were asked to rinse their mouth with 10 ml of 0.2 % chlorhexidine digluconate for 30 s. After rinsing, samples were collected from the interdental area, buccal dental pellicle, anterior labial and posterior buccal mucosa, and saliva with a microbrush at five-time points within 24 h. Retention of chlorhexidine was measured using matrix-assisted laser desorption/ionization-time of flight mass spectrometry with a quantification limit of 15 ng/ml. RESULTS: Chlorhexidine remained in the oral cavity at micrograms per milliliter levels for 11 h after mouth rinsing and was even detected 24 h after application. The results showed a distinct decline of intraoral chlorhexidine levels during the first 6 h after rinsing and it was then retained at low concentrations for at least 24 h. CONCLUSIONS: The dental pellicle and oral mucosa were favorable sites for chlorhexidine retention. The novel method used for chlorhexidine determination offered excellent quantification limits and readily permitted quantification of chlorhexidine.

In Vitro Evaluation of Substantivity, Staining Potential, and Biofilm Reduction of Guava Leaf Extract Mouth Rinse in Combination with its Anti-Inflammatory Effect on Human Gingival Epithelial Keratinocytes.

This study aimed to assess the biofilm reduction, staining potential, and cytotoxicity of guava extract mouth rinse compared to chlorhexidine (CHX). Substantivity, staining, and antibiofilm potential were investigated by spectrophotometry, colony-forming units, and luminosity color meter, respectively. The cell viability assay was conducted using a colorimetric assay to determine nontoxic levels of guava (0.15%) and CHX in human gingival epithelial keratinocytes (HGEK-16). Cells were treated with lipopolysaccharides (LPS, 1µg/mL) and guava to assess inflammatory gene expression levels of interleukin-ß1, tumor necrosis factor-α, and Prostaglandin E2. A scratch wound healing assay investigated the effects of guava on cell migration. The teeth coated in guava mouth rinse displayed 19.4% higher substantivity compared to CHX (0.2%), and the anti-biofilm reduction was observed with both guava and CHX mouth rinses (P < 0.05). The overall discoloration changes were higher with CHX and distilled water compared to guava. Also, guava significantly enhanced HGEK-16 cell viability (P < 0.05), and IL-ß1, TNFα and PGE2 expression presented a 0.6-fold decrease when exposed to guava and LPS (P < 0.05). The present study showed that guava mouth rinse fulfilled the requirement for an effective and useful oral care product with desirable substantivity and anti-biofilm action. In addition, guava reduced the inflammation response in HGEK-16 and may be a potential oral rinse for oral anti-inflammatory therapies.

Optimization of Rheological Behaviour and Skin Penetration of Thermogelling Emulsions with Enhanced Substantivity for Potential Application in Treatment of Chronic Skin Diseases.

Topical formulations are an important pillar in the therapy of skin diseases. Nevertheless, after application the formulation will be exposed to environmental effects. Contact with other surfaces will reduce the available amount of formulation and drug substance. The resulting consequences for therapy range from reduced effects to therapeutic failure. The removed active ingredient also contaminates patients' environment. The aim of this work was to develop preparations that remain at the application site. These will enhance safety and efficiency and thus improve of skin disease therapies. Therefore, we developed polymer-stabilised emulsions that show thermogelling properties. Emulsions with different methyl cellulose concentrations and macrogols of different molecular weights were investigated. The dispersed phase consisted of nonivamide as the active pharmaceutical ingredient, dissolved in medium-chain triglycerides. Rheological properties, droplet size, substantivity and ex vivo penetration experiments were performed to characterise the developed formulations. Droplet size and rheological parameters were affected by the composition of the preparations. The tested formulations showed benefits in their substantivity compared to a conventional semi-solid cream. We found a residual amount of up to 100% at the application site. The drug levels in viable epidermis were in a therapeutic range. The developed emulsions are a promising vehicle to improve therapy for chronic skin diseases.

Medicated Foams and Film Forming Dosage Forms as Tools to Improve the Thermodynamic Activity of Drugs to be Administered Through the Skin.

Medicated foams and film forming systems are dosage forms formulated to undergo a controlled metamorphosis when applied on the skin. Indeed, due to the presence of propellant or a particular air-spray foam pump, a liquid can generate foam when applied on the stratum corneum, or a liquid or conventional dosage form can form on the skin a continuous film as a consequence of the solvent evaporation. Thanks to these controlled modifications, the drug thermodynamic activity increases favoring the skin penetration and, therefore, the bioavailability with respect to conventional semi-solid and liquid dosage forms. Furthermore, the available clinical data also evidence that these dosage forms improve the patient's compliance. The main formulative aspects of medicated foams and film forming systems are reviewed with the aim to underline the possible advantages in terms of biopharmaceutical performances and patient's adherence.

Evaluation of fast-acting bactericidal activity and substantivity of an antiseptic agent, olanexidine gluconate, using an ex vivo skin model.

PURPOSE: We assessed the fast-acting bactericidal activity and substantivity of olanexidine gluconate (OLG) to investigate its remaining bactericidal activity on the skin after rinsing and drying by using an ex vivo Yucatan micropig (YMP) skin model. METHODOLOGY: The fast-acting bactericidal activity was evaluated in pigskin models inoculated with methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, vancomycin-resistant Enterococcus faecalis (VRE), Acinetobacter baumannii, Corynebacterium minutissimum and Cutibacterium acnes. To evaluate substantivity, the YMP skin piece first had 1.5 % OLG, chlorhexidine gluconate (CHG) formulations or 10 % povidone-iodine (PVP-I) applied to it, and was then rinsed with distilled water, incubated for 4, 6, 8 or 12 h and inoculated with the test bacteria (MRSA, S. epidermidis and VRE). The viable bacteria remaining at 1 min of exposure of bacteria were counted to measure the quantity of antiseptic molecules retaining bactericidal activity. To determine the factors contributing to the substantivity, the stratum corneum (SC) of the YMP skin that had had OLG or CHG applied to it was exfoliated using a tape-stripping method and the amount of antiseptic was quantitated. RESULTS: OLG showed a fast-acting bactericidal activity that was similar to or stronger than that of CHG formulations up to a concentration of 1 % and PVP-I with a short exposure time of 30 s, and substantivity until 12 h after rinsing, whereas the other antiseptics hardly showed any substantivity. There was 2.8 times or more OLG in the SC than CHG. CONCLUSION: OLG has fast-acting activity and substantivity, which are required properties for an antiseptic, and is useful for preventing infections.

Method to determine the impact of substantivity on ex vivo skin-permeation.

Topical formulations are the most common therapeutic agents in the treatment of skin diseases. They contain one or more active pharmaceutical ingredients (API) which need to penetrate or permeate the skin in order to exert their effect. However, after application a part of the formulation is removed from the skin due to contact with the environment. Therefore, a part of the active is then not available for penetration and thus, a loss in therapeutic effect will result. To achieve the desired therapeutic outcome a sufficient fraction of the formulation must remain on the skin. The extent to which the loss of preparation affects penetration and permeation is less investigated. This work presents a method to examine the influence of mechanical stress and formulation loss on skin permeation. A movable punch with a defined weight simulated contact between clothing or skin and the applied formulation. Weight of the tool, number of contacts and speed settings were variable and were investigated. Ex vivo permeation experiments were performed in Franz diffusion cells using porcine skin. Three preparations with nonivamide as active ingredient were chosen as model formulations: A semisolid cream, an oil-in-oil emulsion and a film-forming formulation. The last two show sustained permeation profiles. The method uses skin-to-formulation and clothing-to-formulation contact to simulate the removal of the formulations from the skin.

Stratum corneum substantivity: drug development implications.

There are at least 15 factors that influence the ability of chemicals to penetrate the skin. Substantivity is yet another factor and allows penetrants to remain on and in skin for many days. As many skin pathologies involve stratum corneum and require multiple dosing of topicals, understanding substantivity mechanisms may provide insight for topical dosing strategies. Substantivity is also of importance in the development of other consumer products that necessitate adherence to skin, including sunscreens, insect repellents, and cosmetics. Furthermore, while stratum corneum adherence may delay percutaneous penetration, reducing the risk of systemic toxicity, excessive substantivity may play a role in the toxic accumulation of harmful penetrants. Continued research in this area may offer insight into dermatotoxicology and dermatopharmacology.

Evaluation of substantivity of hypochlorous acid as an antiplaque agent: A randomized controlled trial.

BACKGROUND: Hypochlorous acid (HOCl) is a non-antibiotic antimicrobial substance with significant effects on pathogenic oral micro-organisms. The effects of HOCl as an antiplaque agent have not been studied. OBJECTIVE: The aim of this study was to evaluate the substantivity of HOCl mouthwashes compared with chlorhexidine (CHX) rinses and a placebo. MATERIALS AND METHODS: A double-blind randomized controlled trial with 75 participants was conducted. Participants were divided into five groups using block randomization: 0.025% HOCl, 0.05% HOCl, 0.12% CHX, 0.2% CHX, and sterile water as a placebo. Participants were instructed to use each rinse solution for 30 seconds after dental prophylaxis. Samples of saliva were taken at baseline and after 30 seconds, 1, 3, 5 and 7 hours to assess substantivity, and bacterial viability was established by the fluorescence method. Visible plaque in all participants was assessed with the Turesky index at baseline and at 7 hours, and adverse events were also assessed. RESULTS: HOCl led to a 33% reduction in bacterial counts in the saliva after 30 seconds compared with a 58% reduction by CHX. HOCl has no substantivity, and bacterial counts returned to baseline after 1 hour. Placebo treatment led to the highest plaque count after 7 hours compared with the CHX and HOCl groups, although the differences were not significant. HOCl rinsing induced the highest percentages of unpleasant taste and dryness sensations. CONCLUSIONS: HOCl rinses have an initial effect on bacterial viability in saliva but have no substantivity. Other mechanisms may explain its antiplaque effect.

Effect of root canal preparation techniques on chlorhexidine substantivity on human dentin: a chemical analysis.

OBJECTIVES: Chlorhexidine binds to dentine to provide sustained action. The aim of the present study was to evaluate and compare the substantivity of chlorhexidine using manual, rotary, and reciprocating systems for root canal preparation. METHODS: Forty-five extracted human single-rooted teeth were used for this study. The samples were divided into three groups (n = 15) according to the instrumentation technique used: manual instrumentation (K-File), rotary instrumentation (ProTaper), and reciprocating instrumentation (Reciproc R25). Chlorhexidine gel (2%) was used as auxiliary chemical substance during root canal preparation. Longitudinal grooves were carved on the free surfaces of the roots, providing two halves of each root and resulting in 30 samples per group. Each group was randomly divided into three subgroups (n = 10), and substantivity was evaluated after 48 h, 7 days, and 30 days of incubation. The amount of CHX (in mg/mL) was measured through reverse-phase high-performance liquid chromatography. Statistical analysis was performed by analysis of variance and the Tukey test for post hoc comparisons (α = 0.05). RESULTS: The manual did not show a statistical significant difference with rotary instrumentation (P > 0.05), but higher CHX substantivity was recorded in all periods of observation when compared to reciprocating instrumentation (P < 0.05). CONCLUSIONS: The CHX substantivity on human dentine is lowest when using reciprocating compared to manual and rotary instrumentation. CLINICAL SIGNIFICANCE: Using chemical analysis, this study showed that a manual and rotary multi-instrument system results in greater chlorhexidine substantivity on human dentin than a reciprocating single-instrument system.