OBJECTIVES: A commercial Dry Mouth Spray - Biotene®*(Bio) is reported to deliver moistening and lubrication to individuals suffering from lack of salivary flow. This experiment compares the ability of an experimental (Exp**) Dry Mouth Spray vs Biotene® (Bio) to deliver active ingredients (mucoadhesives and a caries inhibitor) over time. A novel apparatus for creation and evaluation of biofilms (Drip Flow Apparatus) was used to simulate the dry mouth oral environment.

DRIP FLOW BIOFILM REACTOR (BIOSURFACE TECHNOLOGIES CORPORATION)

METHODS: According to Ashland Inc. Publication “Lubrajel BA Hydrogel - a Novel Solution for Mouth Moisturization”, Lubrajel provides significant mucoadhesion which allows moisture to stay in contact with the oral environment longer than without Lubrajel. In this Publication, evaluation of experimental formulations containing Lubrajel BA demonstrated higher mucoadhesion than a commercially available control using a urethane substrate to mimic oral mucosa. An Ashland representative indicated the urethane used was Lubrizol Avalure UR425. This product is no longer available, but an equivalent (Lubrizol Avalure AR 450) was substituted in the experiment below.

Plastic microscope slides (2) were weighed (to the nearest 0.001g) and coated with the AR 450 polymer and allowed to dry. The slides were re-weighed to the nearest 0.001g. The slides were then immersed in water (approximately 10 - 15 minutes) to allow the coating to swell slightly and begin looking opaque (too much moisture will cause the polymer to be washed off the surface). The slides were then placed in the Drip Flow Reactor at a 10 degree slope and exposed to deionized water flow of 0.35ml per minute flow for one hour. They were removed and after drying, had no change in weight (+/- 0.002g).

Slides were then similarly coated with the urethane, water treated and then individually over coated with the experimental Dry Mouth Spray or Biotene and weighed wet (to the nearest 0.001g). The slides were the placed into the Drip flow Reactor as before. The slides were removed, dried, and re-weighed to the nearest 0.001g. The residual amount of wet coating (original solution) was determined using the following solids calculations:

*Experimental Dry Mouth Spray - Test Formula INGREDIENTS - FORMULA 021914-1 Xylitol 42% Water * Glycerin * Butylene Glycol * Sodium Polyacrylate * Polyacrylic Acid * Bemzoic Acid * EDTA * Flavor *

*specific percentages are proprietary

Biotene is a product of Glaxo SmithKline who has Gel and Rinse in addition to Dry Mouth Spray. Patent application 20080317703 provides the following compositions for a mouth spray with may be close to that of their commercial product. In the patent application, mucoadhesive character may be provided by cellulose gum, a saccha-ride gum or a polyacrylic acid polymer, or a mixture thereof.

PCT Application 20080317703 - Example FormulasINGREDIENTS FORMULA A FORMULA B Water- 52.940% 51.750%Glycerin - 35.000% 35%xylitol - 7.500% 7.5%VP/VA copolymer - 1.000 % -----PVP - ------ 2.64%PEG 60 Hydrogenated castor oil - 1.600 % 0.85%Flavour ingredients - 0.810% 0.81%Sodium benzoate - 0.500% 0.5%Xanthan gum - 0.400% 0.4%Methylparaben - 0.100% -----Propylparaben - 0.100% ----- Cetylpyridinium chloride - 0.050 0.05%Cellulose Gum - ---- 0.4%Aloe Barbadensis - ------ 0.1%

DETERMINATION OF % SOLIDS: Slides were weighed and then coated with the above formulations using a varnish brush. The amount of solution on each slide was determined by measuring weight loss from the original container. The slides were left to dry and then were re-weighed. The Dry Mouth Spray slide contained 45.8% solids (xylitol + lubrajel polymers). Biotene was similarly applied to a slide and allowed to dry (in this case it took several days at 37C to get to constant weight (+/- 0.002g) and resulted in 52.9% “dry weight. In this case the residual was not completely dry, but rather a thick, tacky layer.

RESULTS: All slides coated with the spray formulas and exposed to the Drip Flow conditions were dried overnight and then weighed. The Experimental Dry Mouth Spray slides had re-sidual weight of 0.020g and 0.031g with the original weights of spray coating at 0.097g and 0.113g. This results in residual Experimental spray residuals of 45.0% and 59.9% respectively. Biotene had no residual coating after the one hour Drip Flow treatment. Biotene slide weights were within 0.001g of the weight before applying the Biotene coating.

EXAMPLE CALCULATION: 100 x residual weight/ (original weight x % solids) 100 x 0.020/(0.097x0.458) = 45.0%

DISCUSSION : The flow rates (target 0.35 ml/min) were chosen to simulate the reduced flow of saliva in a dry mouth compromised patient (typically about 0.3 ml/min) vs a normal flow of 1.0 ml/min. The data definitely show that Lubrajel is effective as a substantive agent for xylitol in the spray formulation. In 2008, So¨derling(1) reported that after consumption of xylitol containing candy, gum and tablets, xylitol showed fast clearance from the oral cavity with only low salivary xylitol levels detected at 8–10 min.

And further reported... In summary, a concentration dependency was seen in the growth inhibition of S. mutans, with 0.01% (0.66 mM) being the lowest xylitol concen-tration significantly inhibiting all five S. mutans strains. Our results suggest that 1% (66mM) was inhibitory at 60% or higher with all strains, a low xylitol concentration of 0.1% (6.6 mM) could inhibit mutans streptococci in vivo (from 21 to 59% depending on strain of S Mutans), but that even lower xylitol concentrations may be inhibitory.

Using an experimental Spray bottle to deliver the Experimental Dry Mouth solution to the mouth with a recommended three compressions, resulted in a dose of 0.63 g. Therefore an initial dose of Xylitol would be 0.88 g/ml (88%) of saliva and the residu-al after one hour would be 0.08g/ml (8%) - 0.153 g/ml (15.3 %). This would imply a residual certainly high enough to inhibit S. Mutans based on the above work.

#1765

Demonstration of Xylitol Substantivity in an Experimental Dry Mouth Spray Authors: J. Swanson1, W. Douglas1, R. Krone2

ABSTRACTOBJECTIVES: A commercial Dry Mouth Spray - Biotene®*(Bio) is reported to deliver moistening and lubrication to individuals suffering from lack of salivary flow. This experiment compares the ability of an experimental (Exp**) Dry Mouth Spray vs Bio to deliver active ingredients (mucoadhesives and a caries inhibitor) over time.

METHODS: Weighed Plastic Slides were coated with a simulated mucosal material (MM) and re-weighed. MM slides were conditioned in water, and left untreated, or coated with Bio or Exp material and weighed again. Each was duplicated. “Dry” weight was determined for each material by allowing the samples to air dry to a constant weight (0.002mg). The slides were placed in a novel Drip Flow Apparatus (DFA) for one hour under simulated Dry Mouth salivary flow (water at 0.35ml/min). The slides were removed, dried and re-weighed to determine residual material.

RESULTS: MM slides were unchanged (<1%) under the test conditions. Bio slides had no residual Bio coating (<2%), Exp slides retained 45.0% and 59.9% - active ingredients xylitol(xyl) and Lubrajel*** BA (Lub) components.

CONCLUSIONS: That substrate MM slides were unchanged indicated further weight changes during the test would be due to the Study material only. Bio results showed no ingredients were pres-ent on the slides. Exp material had significant residuals with large amounts of active materials (primarily xyl with minor amounts of insoluble components of Lub present after one hour at simulated conditions. This demonstrates the Exp material is capable of providing significant amounts of xyl over an extended period. Xyl has been shown to interfere with S Mutans (SM) reproduction. Work is proposed to further investigate Xyl substantivity and SM effects.

*Now AllDayTM Dry Mouth Spray - Elevate Oral Care **Biotene® - GalaxoSmithKline ***Lubrajel - registered trademark of United Guardian Inc.

AUTHORS/INSTITUTIONS: 1) J. Swanson, W. Douglas, MDRCBB, University of Minnesota, St Paul, Minnesota 2) R. Krone, Elevate Oral Care, West Palm Beach, Florida

1- Growth Inhibition of Streptococcus mutans with Low Xylitol Concentrations Curr Microbiol (2008) 56:382–385 Eva M. Söderling, Tiina C. Ekman, Teemu J. Taipale