Method of producing delayed release of sodium fluoride

A process of pretreating a lower alkyl cellulose, such as ethyl cellulose, which is to be used in microencapsulation of sodium fluoride for dental purposes. This process comprises dispersing a predetermined quantity of lower alkyl cellulose in an aqueous mineral acid, such as HCl, and stirring and aqueous washing of the cellulose such that the pH of the product is adjusted to 6.0 or less. This product is later dissolved in a BTX (benzene, toluene, xylene) solvent such as toluene. Sodium fluoride is added and process steps such as baffle stirring and drying are utilized to produce microencapsulation of the sodium fluoride with the lower alkyl cellulose. The process produces an encapsulating material of optimum sodium content and gives release time in water of 2.3-7.0 hours for the sodium fluoride.

The present invention relates generally to the production of a delayed 
release of sodium fluoride, a material important in the field of dentistry 
and specifically in the area of preventive medicine in caries. The 
encapsulation of sodium fluoride is a chronic problem due to its extremely 
polar and hydrophilic qualities. 
PRIOR ART STATEMENT 
U.S. Pat. Nos. 1,448,091 Seel and 1,599,508 Altwegg et al teach the acid 
treatment of ethyl cellulose. 
U.S. Pat. No. 3,049,537 Klug et al teaches the neutralization of 
hydroxyalkyl cellulose ethers with acetic or nitric acid. 
Specifically, this process relates to a pretreatment of the encapsulating 
material, which is a lower alkyl cellulose, the term lower alkyl being 
defined as C.sub.1 -C.sub.6 in the etherifying group on the cellulose. A 
preferred material, of course, is ethyl cellulose (Ethocel, Dow Chemical). 
As generally manufactured, such a lower alkyl cellulose contains ONa 
groups and is the rough input material for the process. 
In a particular illustration, in Step (a) input ethyl cellulose is 
dispersed in aqueous HCl to obtain a product wherein the pH is less than 
6.0. The pH is measured in a benzene/alcohol system 10:90. In Step (b) the 
acidified product from (a) of ethyl cellulose is dissolved in a BTX 
(benzene, toluene, xylene) solvent, such as toluene; then sodium fluoride 
is added with baffle stirring and drying to produce microencapsulation of 
the sodium fluoride with the ethyl cellulose. A product is obtained which 
has a typical size of 40-60.mu.m. The process produces an encapsulating 
material of optimum sodium content and gives release time in water of 
2.3-7.0 hours for the sodium fluoride. 
The advantage in release rate over known methods is substantial for the 
present process. For example, in a typical application of coacervation the 
process will produce microcapsules in the range 140/230 mesh 
(.ident.62-1.5.mu.m) containing 29-33% sodium fluoride, half of which is 
released in water over 2.3-7.0 hours. It has been further noted that 
microcapsules made by the same process but starting with untreated ethyl 
cellulose (pH 7-8) had a half release time in water of 0.7-0.9 hours. 
Further, release from the untreated Ethocel microcapsules was less linear 
than microcapsules made from pretreated ethyl cellulose.

EXAMPLE 
Dow Standard 100 Ethocel (ethyl cellulose) was stirred vigorously in 
distilled water (1 liter for every 80-100 grams) in which 1 N hydrochloric 
acid was added gradually until the pH of the water was approximately 1.0. 
The dispersion was stirred and filtered and the Ethocel was washed 
repeatedly, then dried at a low temperature (&lt;60.degree. C.) at 30 mm Hg 
for 1-11/2 hours. The product was tested by dissolving 2 grams in 100 ml 
of a solution containing 90% ethanol (190 proof) and 10% benzene (w/w). A 
pH reading of 6.0 or less was satisfactory. 
The treated Ethocel was dissolved in toluene to make a 2% w/w solution. The 
solution was stirred at 1000 rpm in a baffled beaker. Three grams of 
finely ground sodium fluoride (size 40-60.mu.m) were dispersed in 300 
grams of solution. 120 grams of poly(dimethylsiloxane) (Dow Corning 360, 
20 centistokes viscosity) were added at a constant rate over a 20-minute 
period followed by 400 ml petroleum ether (b.p. 35.degree.-65.degree. C.) 
over a 4-minute period, then 1.2 liters over a one-minute period. Stirring 
was discontinued after five additional minutes. The supernate was decanted 
and the fluffy white precipitate was washed five times with 400 ml 
portions of petroleum ether. In order to alleviate sticking, the 
precipitate was not allowed to settle completely before each portion of 
petroleum ether was poured off. After the fifth washing, the precipitate 
was filtered, dried (1 hour, 30 mm Hg, 70.degree. C.) and sifted. This 
process produced 1.4-1.8 grams of 140/230 mesh (.ident.62- 105.mu.m) 
microcapsules containing 29-33% sodium fluoride, half of which was 
released in water over 2.3-4.3 hours. If a slower release is desired, 
cyclohexane is mixed with the petroleum ether used in the washing; for 
instance, when the third wash consisted of 40 ml cyclohexane and 150 ml 
petroleum ether, a similar yield of microcapsules which released half of 
their sodium fluoride in 7 hours was obtained. Microcapsules made by the 
same process but starting with untreated Ethocel (pH 7-8) had a half 
release time in water of 0.7-0.9 hours; release from these microcapsules 
was observably less linear than release from microcapsules made with 
pretreated Ethocel. The size and release rate of the microcapsules 
produced in this run was typical of other batches.