orabase and calcium-phosphate--dibasic--anhydrous

Disintegration of immediate release tablets originates from the volume expansion of disintegrants within the formulation. Here, we study the impact of ethanol on the disintegrant expansion and on tablets disintegration. The three most commonly used superdisintegrants, namely sodium starch glycolate (SSG), crospovidone (PVPP) and croscarmellose sodium (CCS) were investigated alone and incorporated in dicalcium phosphate and in drug-containing tablets. High (i.e. 40%), but not moderate (i.e. 10%), aqueous ethanol concentrations reduce the size expansion of the three disintegrants compared to water. This "ethanol effect" is the greatest for SSG, followed by CCS and then PVPP. Moreover, the presence of ethanol in the media can significantly influence the disintegration time of drug-containing tablets via affecting both the disintegrant action itself and the drug solubility. For example, the disintegration time of theophylline tablets containing SSG is 8.1-fold greater in 40% aqueous ethanol compared to water. Overall, this study brought to light the existence of a potentially significant interference of alcohol with the disintegration phenomenon, suggesting that the concomitant administration of tablets and intake of alcoholic beverages may affect, in some cases, tablets disintegration. More studies are now needed to verify the importance of the "ethanol effect" on disintegration of commercial dosage forms. Our findings also suggest that PVPP is the disintegrant that is the least affected by alcohol.

Topics: Calcium Phosphates; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Ethanol; Excipients; Povidone; Solubility; Starch; Tablets; Water

The understanding of tablet disintegration is still incomplete as not all involved factors and processes are known or accounted for. E.g., the negative influence of soluble fillers, on disintegration is usually attributed to increased viscosity due to dissolved filler. When the most common filler, lactose, dissolves, the viscosity increases only slightly. The impact of binders has hardly been studied systematically. In this study, water uptake and force development as well as water sorption experiments were performed of tablets containing either a soluble or an insoluble filler, one of four different binders, and one of four different disintegrants. For both fillers, one disintegrant performed distinctly worse than the others. For the insoluble filler, dibasic calcium phosphate (DCP), sodium starch glycolate resulted in the longest disintegration, for the soluble filler, lactose, croscarmellose sodium performed worst. Based on the experimental results, the authors introduce the competition-for-water hypothesis, which takes into consideration the amount of freely available water molecules and hydration kinetics of excipients. Soluble fillers bind a large number of water molecules in hydrate shells and prevent, therefore, proper disintegrant action. Previously inconsistent observations can be approached with this hypothesis and a better understanding of the underlying processes and explanations is possible.

Topics: Calcium Phosphates; Carboxymethylcellulose Sodium; Excipients; Lactose; Particle Size; Polymers; Solubility; Tablets; Viscosity; Water

The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a Consigma™-1 twin screw granulator. Process conditions including powder feed rate, liquid to solid ratio, granulation liquid composition and screw configuration were also evaluated. The size of the wet granules was measured in order to enable exploration of granulation behaviour in isolation without confounding effects from downstream processes such as drying. The experimental observations indicated that the granulation process was not sensitive to the powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and hence a relatively large proportion of un-wetted particles. Increasing numbers of kneading elements led to high shear and prolonged residence time, which acted to enhance the distribution of liquid and feeding materials. The bimodal size distributions considered to be characteristic of twin screw granulation were primarily ascribed to the breakage of relatively large granules by the kneading elements.

Topics: Calcium Phosphates; Carboxymethylcellulose Sodium; Cellulose; Chemical Phenomena; Chemistry, Pharmaceutical; Drug Compounding; England; Excipients; Hydrophobic and Hydrophilic Interactions; Lactose; Materials Testing; Particle Size; Placebos; Quality Control; Reproducibility of Results; Surface Properties; Time Factors; Water

Treatments that obdurate dentin tubules have been used for reducing dentin hypersensitivity. The purpose of this study was to determine the effect of a treatment with a slurry of micron sized calcium phosphate on the hydraulic conductance (L(p)) of etched dentin discs in vitro. The treatment slurry was prepared by mixing a powder mixture of dicalcium phosphate anhydrous and calcium hydroxide with a solution that contained sodium fluoride and carboxymethyl cellulose. The mean baseline L(p) (in mL cm(-2) s(-1) H(2)O cm(-1)) was 2.07 +/- 1.45 (mean +/- SD; n = 13)). After one treatment and 2, 4, and 7 days of incubation in a protein-free saliva-like solution (SLS), the mean relative L(p), presented as % of baseline, were 65 +/- 16, 42 +/- 27, 36 +/- 26, and 33 +/- 27 (n = 13), respectively. The L(p) values of the baseline and treatment after incubation in the SLS were significantly (p < 0.05) different. Scanning electron microscopic examination showed partial obturation of dentin tubules in the treated dentin. X-ray diffraction and chemical analyses indicated the major product formed from the slurry was a fluoride-containing hydroxyapatite. Treatment appeared effective in further reducing L(p) of dentin discs after incubation in the SLS.

Topics: Calcium Hydroxide; Calcium Phosphates; Carboxymethylcellulose Sodium; Dentin; Dentin Permeability; Humans; Sodium Fluoride; Time Factors

The calcium phosphate cement (CPC) used in this study was formed by combining equimolar amounts of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). This powder, when mixed with water, sets to a hard cement in about 30 min. However, the water-based CPC paste is not highly cohesive and is vulnerable to washout until hardening occurs. The objectives of this study were to investigate the effects on handling properties, washout resistance, cement hardening behavior, and mechanical properties of adding several gelling agents to CPC paste. Aqueous solutions that contained a mass fraction of 2-4% of hydroxypropyl methylcellulose (HPMC), carboxyl methylcellulose (CMC), chitosan acetate, and chitosan lactate were used as cement liquids. Hardening time was measured by the Gilmore needle test; resistance to washout was evaluated by the disintegration of the cement specimen in water with agitation; and mechanical strength was evaluated by the measurement of diametral tensile strength and compressive strength. Handling properties were greatly improved by the addition of HPMC, CMC, chitosan acetate, and chitosan lactate. Hardening time was retarded by the additions of HPMC and CMC, and mechanical strength was weakened by the addition of either the chitosan lactate or the chitosan acetate.

Topics: Biocompatible Materials; Calcium Phosphates; Carboxymethylcellulose Sodium; Chitin; Chitosan; Dental Cements; Hypromellose Derivatives; Materials Testing; Methylcellulose; X-Ray Diffraction

A number of polymers which have previously been tested for their applicability as thickening agents in saliva substitutes were studied in vitro for their caries-protective properties. These were: polyacrylic acid, carboxymethylcellulose, xanthan gum, guar gum, hydroxyethylcellulose and porcine gastric mucin. The polymers were tested for their effects on: (1) growth of hydroxyapatite crystals in a supersaturated calcium phosphate solution, (2) dissolution of hydroxyapatite crystals in 50 mM acetic acid, pH 5.2 and (3) demineralization and remineralization of bovine enamel in a pH-cycling model. Growth of hydroxyapatite crystals was strongly inhibited by polyacrylic acid and carboxymethylcellulose at very low concentrations (0.005% w/v). Other polymers displayed lower inhibition of hydroxyapatite crystal growth. Hydroxyapatite dissolution was inhibited by all polymers except by hydroxymethylcellulose and xanthan gum. This occurred both in the presence of the polymers as well as after a 30-min preincubation. In the pH-cycling experiment, bovine enamel specimens with preformed lesions were alternately exposed to a demineralization buffer and a remineralization buffer containing the polymers hydroxyethylcellulose, carboxymethylcellulose, xanthan gum, polyacrylic acid, or porcine gastric mucin. A remineralization buffer containing 1 ppm NaF was used as a positive control. Under the experimental conditions, the control experiment without additives resulted in a net mineral loss (30.6 mumol Ca/cm2 after 14 days of pH cycling). In the presence of 1 ppm NaF, a small mineral gain was observed (8.6 mumol/cm2). All polymers largely inhibited further demineralization (1.2-12.3 mumol/cm2) except polyacrylic acid which, inhibited of its high calcium-binding capacity, caused demineralization, especially in the remineralization buffer (17.1 mumol/cm2). In conclusion, polymers tested in this study, except the polyacrylic acid, reduced the demineralization of enamel in vitro. The precise mechanism of the protective effect is not clear but it is speculated that formation of an absorbed polymer layer on the hydroxyapatite or enamel surface may provide protection against acidic attacks.

Topics: Acetic Acid; Acrylic Resins; Adsorption; Animals; Buffers; Calcium Phosphates; Carboxymethylcellulose Sodium; Cariostatic Agents; Cattle; Cellulose; Crystallization; Dental Enamel; Dental Enamel Solubility; Durapatite; Galactans; Humans; Hydrogen-Ion Concentration; Mannans; Mucins; Plant Gums; Polymers; Polysaccharides, Bacterial; Saliva, Artificial; Sodium Fluoride; Solubility; Swine; Tooth Demineralization; Tooth Remineralization

The aim of the present work was to optimize a tablet formulation containing a physical mixture of a practically insoluble drug (prednisone) with a superdisintegrant (croscarmellose sodium) and two filler-binders characterized by differing water solubility (dicalcium phosphate dihydrate and anhydrous beta-lactose). Crushing strength, disintegration, and dissolution were measured for 10 formulations distributed over a factor space according to a simplex lattice design for a special cubic model. Multiple linear regression analysis was used to assess the best fit for each variable. The model predicted that increasing the amount of disintegrant to a critical amount (50%) would result in reduced disintegration time for dicalcium phosphate/beta-lactose ratios > 0.3, no changes in disintegration time for ratios < 0.3, and for all ratios an improvement in dissolution at 10 min. Crushing strength values of dicalcium phosphate increased with increasing disintegration concentration but not for beta-lactose tablets. The physical mixture of a practically insoluble drug with a superdisintegrant was confirmed as a valid approach to the improvement of dissolution, even in presence of other components. The solubility of the filler-binders influenced the minimum amount of disintegrant needed; when a soluble diluent was used, the amount of disintegrant required was reduced.

Topics: Anti-Inflammatory Agents; Calcium Phosphates; Carboxymethylcellulose Sodium; Excipients; Hardness Tests; Kinetics; Lactose; Prednisone; Regression Analysis; Solubility; Stearic Acids; Tablets