Preparation and evaluation of orally disintegrating tablets containing taste masked microparticles of acetaminophen.

In the present work, taste masked particles of acetaminophen (AAP), a highly soluble bitter tasting drug, were developed and ODT containing the taste masked particles were prepared. Taste masked particles of AAP were prepared using different amounts of tetraglycerol polyricinoleate (TGPR) and Eudragit ®E100. Although the drug content ratio and drug recovery decreased with increasing TGPR, drug release from AAP-CR100 particles containing a large amount of TGPR was mostly suppressed for 2 min. Hence, AAP-CR100 was incorporated into ODT as taste masked particles for AAP. Three major disintegrants were used for ODT, and it was confirmed that the tensile strength of all formulations showed applicable hardness for handling. The AAP-CR100-CP(40) formulation containing crospovidone showed the shortest disintegration time and the drug release from AAP-CR100-CP(40) into pH 6.8 test solution was suppressed compared with commercial AAP tablets. Because the drug release from AAP-CR100-CP(40) into the pH 1.2 test solution was rapid, it was suggested that drug release from AAP-CR100-CP(40) is suppressed in the oral cavity, and the drug is released promptly in the stomach. Thus AAP-CR100-CP(40) may be useful as an ODT in which the dissolution of AAP in the oral cavity is suppressed.

Inhibition of the formation of oral calcium phosphate precipitates: the possible effects of certain honeybee products.

BACKGROUND AND OBJECTIVE: We studied the effects of honeybee products on the in vitro formation of calcium phosphate precipitates. MATERIAL AND METHODS: Screening tests of the in vitro formation of calcium phosphate precipitates using 20 types of honey and four types of propolis were carried out using the pH drop method. RESULTS: The inhibitory effect on the rate of amorphous calcium phosphate transformation to hydroxyapatite and on the induction time varied greatly among the 20 types of honey and four types of propolis. We classified them according to their effects on decreasing the rate of amorphous calcium phosphate transformation to hydroxyapatite and/or increasing the induction time. Two of the 20 honeys showed little or no inhibition, either on the rate of amorphous calcium phosphate transformation to hydroxyapatite or on the induction time. Six of the honeys reduced the rate of amorphous calcium phosphate transformation to hydroxyapatite by 12-35% and with a 2.5- to 4.4-fold increase in the induction time. The remaining 12 honeys showed even greater activity. Because four of these 12 honeys had an inhibitory effect on the rate of amorphous calcium phosphate formation, they were excluded as candidates for anticalculus agents. Furthermore, three of the four types of propolis showed an inhibitory effect that was the same as or greater than 1-hydroxyethylidene- 1,1-bisphosphonate. CONCLUSION: These results suggest that eight honeys and three types of propolis may have potential as anticalculus agents in toothpastes and mouthwashes.

An ionic polymer bead-supported lipid system.

In this paper, we report on the preparation of an ionic polymer bead-supported lipid system several hundred micrometers in diameter. The electrostatic attractive interactions between anionic lipids and cationic polymer beads served as a "molecular glue" to immobilize the lipids on the beads, and then the immobilized lipids prompted the spontaneous formation of lipid bilayer membranes. Confocal fluorescence microscopic techniques revealed that the lipid bilayer membranes were located along the outline of the beads. In addition, the integrity of the lipid bilayer membranes was microscopically confirmed by a low-molecular-weight dye (trypan blue) exclusion test.

The effects of tyramine on salivary flow rate and protein secretion by rat submandibular glands.

The effects of different doses of p-tyramine injected i.v. and i.p. on salivary flow rates and proteins secreted by the submandibular glands of rats were studied with and without various types of autonomic blockers and two enzyme inhibitors. The salivary flow rates and the amounts of protein secreted progressively increased with increasing doses injected both i.v. and i.p., whereas they were dramatically reduced with all autonomic blockers except the lowest doses of beta-blockers, atropine, and yohimbine. Salivation in response to p-tyramine injected i.v. and i.p. was completely abolished by simultaneous injections of both prazosin and propranolol. The concentration of protein was not dose-dependent and was not reduced by yohimbine and phenoxybenzamine at almost all doses used. However, prazosin significantly increased the protein concentration. Protease activities were dose-dependent but were significantly reduced with alpha-blockers other than yohimbine, and with most beta-blockers. The proteins secreted in response to p-tyramine at all doses injected i.v. and i.p. were of the alpha-type except with the lowest dose injected i.p. However, the alpha-type was completely replaced by the beta-type in the presence of all alpha-blockers except yohimbine, but not with beta-blockers, atropine, or two enzyme inhibitors. Pargyline, a monoamine-oxidase inhibitor, but not disulfiram, a dopamine-beta-hydroxylase inhibitor, affected all parameters except the type of protein. Thus, p-tyramine may activate both the alpha 1- and beta 1-adrenoceptors in the submandibular glands of rats directly or indirectly.

Developmental changes in the volumes, protein, and some electrolyte concentrations of male and female rat submandibular saliva secreted in response to methoxamine and pilocarpine.

Saliva secreted in response to methoxamine and pilocarpine was collected from the cannulated ducts of the submandibular glands of male and female rats at weekly intervals from two to 10 weeks of age. It was analyzed for volume and for concentrations of protein, potassium, calcium, and inorganic phosphate. Following the collection of saliva, the submandibular glands were removed and weighted. The wet weights of the glands increased substantially up to seven weeks of age and then reached almost plateau values in both sexes. The salivary volumes secreted in response to both agents in both sexes were positively correlated with the gland weights, except that after five to six weeks of age there was no correlation between gland weight and methoxamine-stimulated salivary volume. The concentrations of protein, potassium, and inorganic phosphate were inversely related to the flow rates only at relatively low rates of flow. The concentration of calcium was positively correlated with the protein concentration and was independent of the nature of the stimulus and of sex differences during postnatal development.

The effects of sodium lauryl sulphate and its oxidative breakdown products on calcium phosphate precipitation and transformation.

Most commercial dentifrices contain sodium lauryl sulphate, which oxidizes upon storage. The effects of aged sodium lauryl sulphate and its oxidative breakdown products on the conversion of amorphous calcium phosphate to hydroxyapatite were studied in vitro by a pH drop method. Hydroxyapatite was identified from its X-ray diffraction pattern. With storage time, the concentration of dodecanol [CH3(CH2)11OH], a breakdown product of sodium lauryl sulphate, increased. The storage dodecanol-containing sodium lauryl sulphate accelerated the conversion of amorphous calcium phosphate to hydroxyapatite. Dodecanol mixed with sodium lauryl sulphate accelerated the conversion when added both before and after initial formation of amorphous calcium phosphate. A stored commercial dentifrice also accelerated the conversion of amorphous calcium phosphate to hydroxyapatite. It was found that the concentration of dodecanol increased 2-fold over a 2-month period.

Possible regulatory roles of silicic acid, silica and clay minerals in the formation of calcium phosphate precipitates.

The effects of silicic acid, silica and clay minerals on the conversion of amorphous calcium phosphate to hydroxyapatite (HAP) were studied in vitro by a pH drop method. At a concentration range of 0.01-0.1 mM. silicic acid stimulated the rate of HAP transformation by about 30-40%. Silica stimulated the rate of HAP transformation by 33-43% at a concentration range of 0.05-1.5 mg/ml. The clay minerals, i.e. kaolin and talc, also stimulated the rate of HAP transformation by 40-90% at a concentration range of 0.4-10 mg/ml, but mica inhibited the reaction markedly at 10 mg/ml. The distribution of silicon in human supragingival dental calculus was studied by an electron-probe microanalyser. We found localized silicon distribution on the oral surface of the calculus. Such silicon-rich areas always contained silicon either alone or together with magnesium, aluminium, potassium, calcium and iron. This implies that the silicon-rich area may be opal and mica. Because silicic acid, silica, kaolin and talc stimulated and mica inhibited the in vitro calcium phosphate precipitation, it is possible that these silicon-rich areas may regulate the formation of the dental calculus.

In vitro and in vivo evaluations of Chinese traditional (kampo) medicines as anticalculus agents in the rat.

Inhibitory effects of two Chinese traditional (Kampo) medicines, Shigyaku-san and Shikunshi-to, on the in vitro formation of calcium phosphate precipitates and the in vivo deposition of supragingival dental calculus were studied. Both had inhibitory effects on hydroxyapatite transformation and induction; effects of Shigyaku-san and Shikunshi-to were 1/100 and 1/400 of that of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP). When used topically (in drinking water) for 4 weeks, 20-40 mg/ml of Shigyaku-san or Shikunshi-to reduced the formation of dental calculus by 40-60%, while 0.03% (w/v) HEBP decreased it by 70-98%. However, when these drugs were given by gastric intubation for 2 weeks, they were all ineffective, suggesting that the observed anticalculus effects were of topical rather than of systemic origin.

Localized silicon distribution in supragingival calculus from Japanese monkeys (Macaca fuscata).

Using an electron-probe microanalyser, the distribution of silicon and other elements in supragingival dental calculus in domestic Japanese monkeys (Macaca fuscata) was studied. In two out of four monkeys kept in animals centres, a localized silicon distribution was found in both fracture and oral surfaces of the calculi. The silicon-rich area consisting of silicon alone resembled opal, but the areas containing silicon and other metal ions such as magnesium, aluminium, potassium and iron resembled clay minerals. In eight domestic monkeys, including the four animals described above, abundant calculus deposits were found. However, in four captured wild monkeys and in one which had been kept for less than a year at an animal centre, no dental calculus was found. There was almost no dental plaque accumulation in captured wild monkeys. It is suggested that calculus formation in Japanese monkeys is dependent on length of exposure to a commercial diet.

Morphology and morphometry of skulls of raccoon dogs, Nyctereutes procyonoides and badgers, Meles meles.

In order to obtain the basic data to identify the skeletal remains from the archaeological sites, morphological and morphometrical studies were carried out on skulls of living raccoon dogs (35 males and 45 females) and badgers (16 males and 8 females) from Kagoshima Prefecture. Macroscopically, the sexual differences were observed in badgers for the parts of the zygomatic process of the temporal bone and the occipital squama, but were not in raccoon dogs. Among 24 cranial measurements, significant sexual differences were found in five measurement items in raccoon dogs, while 12 items in badgers. Mandibles showed significant sexual differences in both species. Raccoon dogs had significantly larger values than badgers in most of the items concerning length of cranium and most mandibular measurements. The discrimination efficiencies of discriminant formulae between both sexes were lower in raccoon dogs, but higher in badgers, and the efficiencies between both species were obtained 100%. In the regression formulae for estimating skull length, some formulae showed high coefficients of determination in both species. These observations represented interspecific and sexual differences in the skulls of raccoon dogs and badgers.

An in vitro study of the effect of some dietary components on calculus formation: regulation of calcium phosphate precipitation.

OBJECTIVE: We studied the effects of food components on the in vitro formation of calcium phosphate precipitates. MATERIALS AND METHODS: The effects of food components, such as starch, soybean flour, fish meal, rapeseed oil, and coconut oil, on calcium phosphate precipitation were studied using a pH drop method. RESULTS: Although the addition of starch had no effect on the rate of precipitation of amorphous calcium phosphate (ACP), it increased both the rate of transformation of ACP to hydroxyapatite (HAP) and the induction time (i.e. time for the initiation of transformation of ACP to HAP to occur); this was irrespective of the heat treatment of the starch. Amylopectin (insoluble constituent of starch) was effective in increasing the rate of HAP transformation, but amylose (soluble constituent of starch) was not. Oil specimen obtained from rapeseed (400 microl ml(-1)) increased the entire reaction of calcium phosphate precipitation, but that from coconut did not. Protein food, such as soybean flour and fish meal, decreased the rate of transformation of ACP to HAP and increased the induction time, while they had no effect on the rate of ACP precipitation. CONCLUSION: These results suggest that carbohydrate and oil (both are staple diets for the humans) enhance oral calcification (dental calculus formation or re-mineralization of tooth enamel), while side dishes of protein food would decrease it.

Studies on calcium phosphate precipitation: effects of metal ions used in dental materials.

The effects of 26 metal ions, of which 23 are used in dental materials, on the conversion of amorphous calcium phosphate (ACP) to hydroxyapatite (HAP) in vitro were studied. From the effects on both the rate of HAP transformation and induction time, effects of metal ions were classified into three types; inhibitory (in the order: nickel, tin, cobalt, manganese, copper, zinc, gallium, thallium, molybdenum, cadmium, antimony, magnesium, and mercury); ineffective (cesium, titanium, chromium, iron [ferrous], iridium, palladium, platinum, silver, gold, aluminum, and lead); and stimulatory (iron [ferric] and indium). These results suggest that metal ions used in dental materials may modify the precipitation of oral calcium phosphate.

Elutions of metal ions from dental casting alloys and their effect on calcium phosphate precipitation and transformation.

The elution characteristics of metal ions from dental casting alloys were studied in vitro. Large amounts of nickel (0.12-4.94 mg/cm2) and chromium (< 0.01-0.63 mg/cm2) were solubilized from the surface of seven brands of nickel-chromium alloy in either 1% lactic acid or 0.05% hydrochloric acid solutions. The elution of chromium from two brands of cobalt-chromium alloys in both eluents was below the detection limit or less than 0.01 mg/cm2. The elution of tin, copper, and zinc from a gold-palladium-silver alloy in both eluents was below the detection limit or less than 0.01 and 0.04 mg/cm2. Some amounts of tin (0.19-1.92 mg/cm2) and zinc (0.56-1.73 mg/cm2) were eluted from a silver alloy in both eluents. The effects of five eluting metal ions, i.e., nickel, chromium, tin, copper, and zinc, on the conversion of amorphous calcium phosphate (ACP) to hydroxyapatite (HAP) in vitro also were studied by a pH drop method. All divalent cations except for chromium decreased the rate of HAP transformation and elongated the induction time. Nickel had an inhibitory effect comparable to 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) on the rate of HAP transformation. Tin, copper, and zinc inhibited similarly, but the inhibition was weaker than that by nickel. Chromium did not inhibit these reactions.

Inhibition of the formation of oral calcium phosphate precipitates: beneficial effects of Chinese traditional (kampo) medicines.

Screening tests on the formation of calcium phosphate precipitates using 23 different kinds of Kampo medicines (Chinese traditional medicines) were carried out, at concentrations where the effects of chelation are not significant. Four of them, Hochu-ekki-to (TJ-41), Kyuki-kyogai-to (TJ-77), Oren-to (TJ-120) and Inchin-ko-to (TJ-135) showed an inhibitory effect on the formation of amorphous calcium phosphate (ACP). The inhibitory effect on the induction time and the rate of transformation to hydroxyapatite (HAP) varied greatly among the 23 Kampo medicines. We classified them according to their effects on increasing the induction time and/or decreasing the rate of HAP transformation. Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was used as the standard. This compound is a common toothpaste additive which decreases dental calculus formation. Two of the 23 Kampo medicines showed little or no inhibition either on the induction time or on the rate of HAP transformation. Twelve of them reduced the rate of HAP transformation by 20-40% and with 1.9- to 4.0-fold increases in the induction time. The remaining nine showed even greater activity. Keishi-ninjin-to (TJ-82), Dai-kenchu-to (TJ-100), Toki-to (TJ-102), Rikko-san (TJ-110) and San'o-shashin-to (TJ-113) showed the same inhibitory effect as EHDP. Shigyaku-san (TJ-35;5.2-fold), Dai-kanzo-to (TJ-84;4.9-fold), Oren-gedoku-to (TJ-15;12.7-fold) and Inchin-ko-to (TJ-135;9.5-fold) had a greater effect on the increase of induction time than EHDP and reduced the rate of HAP transformation by 50-60%. These results suggest that these nine kinds of Kampo medicines may have potential as anticalculus agents in toothpastes and mouthwashes.

Effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates.

Inhibitory effects of a rhubarb (Rhei rhizoma) solution and its fractions on the formation of calcium phosphate precipitates were studied. The rhubarb solution inhibited both the amorphous calcium phosphate (ACP) formation and the rate of hydroxyapatite (HAP) transformation, and extended the induction time. When the solution was fractionated using membrane filters, a filtrate with the molecular weight between 3 and 10 kDa (with 2/3 recovery of polyphenols) was found to be responsible for both the ACP formation and the extension of the induction time. Another filtrate with the molecular weight below 3 kDa (with 1/3 recovery of polyphenols) may be responsible for the inhibition of both the ACP formation and the rate of HAP transformation, and the extension of the induction time. When the extract of rhubarb was fractionated using a Sephadex LH-20 column chromatography, fraction IV greatly inhibited the formation of calcium phosphate precipitates, while fractions I, II and III slightly inhibited that reaction. Our finding suggests that fraction IV may contain useful substance(s) for the prevention of oral calcium phosphate precipitation (calculus formation). However, strong calcium chelating properties would limit the concentration that could be safely employed.

Effects of indium and iron ions on in vitro calcium phosphate precipitation and crystallinity.

The elution characteristics of indium and iron ions from six kinds of dental casting alloys were studied in vitro. A certain amount of indium (0.01-1.70 mg/cm2) was solubilized from the surface of only one prosthetic semiprecious brand (Miro Bright) in either 1% lactic acid or 0.05% hydrochloric acid solutions. The elution of iron was below the detection limit or < 0.01 mg/cm2. We also studied the stimulatory effects of indium and ferric ions on the calcium phosphate precipitation in the absence and presence of an inhibitor (phosvitin, a phosphoprotein purified from egg yolks). Indium and ferric ions promoted the reaction, and their stimulatory effects were stronger than the inhibitory effects of phosvitin (250 micrograms/ml). These facts suggest that indium, but not iron, could be eluted into the mouth, and that the eluted indium may stimulate the formation of oral calcium phosphate precipitates, counteracting the inhibition by saliva-derived phosphoproteins. The effects of these metal ions on calcium phosphate precipitates were also studied using both X-ray diffractometry and infrared spectrophotometry. It was shown that both indium and ferric ions decreased the grade of crystallinity of the calcium phosphate precipitates (hydroxyapatite).

Alterations in the periodontium after ovariectomy in rats: the effects of a Japanese herbal medicine, Chujo-to.

Ovariectomy-induced changes on the periodontium (gingiva, alveolar bone, and periodontal ligament) in rats and the preventive effects of a Japanese herbal medicine, Chujo-to, were studied for a period of 49 days. The rats were divided into five groups: sham-operated (sham), ovariectomized (OVX), OVX given Chujo-to, OVX given 17beta-oestradiol, and OVX given the vehicle for 17beta-oestradiol, respectively. After the test period, the bone mineral content (BMC) of the mandibular condyle in OVX rats was similar to those in both sham rats and the OVX rats treated with either Chujo-to or 17beta-oestradiol. However, the scanning electron microscopic (SEM) analyses revealed that the periodontal ligament of the OVX rats and the OVX rats treated with Chujo-to became more coarse than that of the sham rats or the rats treated with 17beta-oestradiol. The surface of the alveolar bone in the OVX rats appeared to contain numerous small granules, which were not present in the sham rats and the rats treated with either Chujo-to or 17beta-oestradiol. These results suggest that ovariectomy caused alterations in the peridontium, but Chujo-to had a preventive effect on the surface architecture of the alveolar bones.