fumarates and sodium-stearyl-fumarate

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (

Topics: Calorimetry, Differential Scanning; Drug Stability; Fumarates; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

Orally dissolving tablets (ODTs) represent one of the recent advances in drug delivery. The foremost objective of this study was to optimize the utilization of lubricant sodium stearyl fumarate in the preparation of dextromethorphan hydrobromide ODTs with enhanced taste-masking properties. The simple blending of sodium stearyl fumarate with the powder bed would result in taste-masking through physical adsorption of the lubricant particles on the drug particles. A randomized 3

Topics: Administration, Oral; Antitussive Agents; Dextromethorphan; Drug Compounding; Excipients; Fumarates; Hardness; Solubility; Tablets; Taste

As an essential formulation component for large-scale tablet manufacturing, the lubricant preserves tooling by reducing die-wall friction. Unfortunately, lubrication also often results in adverse effects on tablet characteristics, such as prolonged disintegration, slowed dissolution, and reduced mechanical strength. Therefore, the choice of lubricant and its optimal concentration in a tablet formulation is a critical decision in tablet formulation development to attain low die-wall friction while minimizing negative impact on other tablet properties. Three commercially available tablet lubricants, i.e., magnesium stearate, sodium stearyl fumerate, and stearic acid, were systematically investigated in both plastic and brittle matrices to elucidate their effects on reducing die-wall friction, tablet strength, tablet hardness, tablet friability, and tablet disintegration kinetics. Clear understanding of the lubrication efficiency of commonly used lubricants as well as their impact on tablet characteristics would help future tablet formulation efforts.

Topics: Drug Compounding; Fumarates; Hardness; Lubricants; Powders; Stearic Acids; Tablets; Tensile Strength

To develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status.. A nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the HPMC matrix tablets in different locations of the gastrointestinal tract, determined by magnetic marker monitoring. In each gastrointestinal segment the pH was set to physiological values and mechanical stress was estimated in USP2 apparatus rotation speed equivalent.. Erosion was best described by a Michaelis-Menten type model. The maximal HPMC release rate (V. The in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets.

Topics: Adult; Calcium Phosphates; Chemistry, Pharmaceutical; Colon; Computer Simulation; Delayed-Action Preparations; Fasting; Ferric Compounds; Fumarates; Gastric Mucosa; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestine, Small; Male; Postprandial Period; Solubility; Stress, Mechanical; Tablets

This study investigates the effects of a variety of coating materials on the flowability and dissolution of dry-coated cohesive ibuprofen powders, with the ultimate aim to use these in oral dosage forms. A mechanofusion approach was employed to apply a 1% (w/w) dry coating onto ibuprofen powder with coating materials including magnesium stearate (MgSt), L-leucine, sodium stearyl fumarate (SSF) and silica-R972. No significant difference in particle size or shape was measured following mechanofusion with any material. Powder flow behaviours characterised by the Freeman FT4 system indicated coatings of MgSt, L-leucine and silica-R972 produced a notable surface modification and substantially improved flow compared to the unprocessed and SSF-mechanofused powders. ToF-SIMS provided a qualitative measure of coating extent, and indicated a near-complete layer on the drug particle surface after dry coating with MgSt or silica-R972. Of particular note, the dissolution rates of all mechanofused powders were enhanced even with a coating of a highly hydrophobic material such as magnesium stearate. This surprising increase in dissolution rate of the mechanofused powders was attributed to the lower cohesion and the reduced agglomeration after mechanical coating.

Topics: Fumarates; Ibuprofen; Leucine; Models, Chemical; Particle Size; Powders; Rheology; Silicon Dioxide; Solubility; Stearic Acids; Surface Properties

Base on the Kawakita powder compression equation, a general theoretical model for predicting the compression characteristics of multi-components pharmaceutical powders with different mass ratios was developed. The uniaxial flat-face compression tests of powder lactose, starch and microcrystalline cellulose were carried out, separately. Therefore, the Kawakita equation parameters of the powder materials were obtained. The uniaxial flat-face compression tests of the powder mixtures of lactose, starch, microcrystalline cellulose and sodium stearyl fumarate with five mass ratios were conducted, through which, the correlation between mixture density and loading pressure and the Kawakita equation curves were obtained. Finally, the theoretical prediction values were compared with experimental results. The analysis showed that the errors in predicting mixture densities were less than 5.0% and the errors of Kawakita vertical coordinate were within 4.6%, which indicated that the theoretical model could be used to predict the direct compaction characteristics of multi-component pharmaceutical powders.

Topics: Cellulose; Excipients; Fumarates; Lactose; Models, Chemical; Powders; Pressure; Starch; Technology, Pharmaceutical

The compound excipient containing sodium stearyl fumarate and plasdone S-630 was prepared by applying spray drying method. The basic physical properties of compound excipient were studied by solubility test, scanning electron microscope, differential scanning calorimeter, X-ray diffraction and Fourier transform infra-red spectroscopy. The effect of compound excipient on moisture absorption and ferulic acid in vitro dissolution of spray drying power of angelica were investigated. The results showed that the chemical constituents of compound excipient did not change before and after spray drying. The water soluble compound excipient can improve significantly moisture absorption and has application prospect.

Topics: Acetates; Calorimetry, Differential Scanning; Coumaric Acids; Drug Compounding; Excipients; Fumarates; Microscopy, Electron, Scanning; Particle Size; Povidone; Solubility; Spectroscopy, Fourier Transform Infrared; Surface Properties; Wettability; X-Ray Diffraction

The evaluation of lubricity or flowability of pharmaceutical powders is important for consistent production and quality control of drug products. However, there have been only a few studies on quantitative measurements of the properties of lubricated powders.. Magnesium stearate (MgSt) and sodium stearyl fumarate (SSF) were used as lubricants. Lubricated powders were prepared by adding lubricants to spray-dried lactose under different conditions. To evaluate flowability, the vibrating tube method was used. In this method, the vibration amplitude of the tube is increased at a constant rate, and the mass of the powder discharged from the tube is recorded. Flowability profiles, i.e. the relationships between the mass flow rate and vibration acceleration, were obtained experimentally. To characterize static and dynamic friction properties of powders, critical vibration acceleration required to make powder particles flow and the average mass flow rate were determined.. Addition of 0.5% MgSt was sufficient for the reduction of static friction between particles. Blending time of the lubricants had little effect on the average mass flow rate of lubricated powders. On the other hand, addition of SSF resulted in an increase in static friction at the beginning of blending, and after a certain blending time, flowability improved. The combination of MgSt and SSF improved both static and dynamic friction properties irrespective of the blending time.. The vibrating tube method can be used to evaluate the flowability properties of lubricated powders, and the experimental results provide useful information on the production of pharmaceutical solid dosage forms.

Topics: Fumarates; Lubricants; Powders; Stearic Acids; Technology, Pharmaceutical; Vibration

The aim of this study was to develop a pH-independent extended release matrix tablet of minocycline HCl for the treatment of dementia. The matrix tablets were prepared by wet granulation technique using Eudragit L and S as release modifiers at different w/w ratios (1:0, 1:1 and 0:1) and PEO as a matrix former. In the case of the matrix tablet without any release modifiers, the drug release rate at pH 1.2 was much higher than that of pH 7.4. By adding the release modifier, the drug release rate at pH 7.4 increased close to that of pH 1.2 and the pH-independent release was obtained. In addition, it was shown that lubricants containing a divalent cation such as Mg stearate inhibited minocycline release in basic medium. Therefore, the incorporation of Eudragit L and S (1:1 ratio) as release modifiers and Na stearyl fumarate as a lubricant into PEO-based matrix tablets effectively produced pH-independent minocycline release profiles.

Topics: Animals; Anti-Bacterial Agents; Delayed-Action Preparations; Dementia; Excipients; Fumarates; Humans; Hydrogen-Ion Concentration; Lubricants; Minocycline; Polyethylene Glycols; Polymethacrylic Acids; Tablets

Direct tableting is simpler and more cost-effective from the point of view of good manufacturing practice (GMP) than wet granulation or dry compacting. Moreover, the use of dry plant extracts in the process of direct tableting, omitting granulation, decreases the possibility of biological activity loss of active substances. Thus, pharmaceutical industry uses this particular process more and more frequently. Only few therapeutic substances form under compression tablets meeting current requirements. Very often addition of auxiliary substances appears to be indispensable. The aim of this study was to obtain uncoated tablets by the method of direct tableting with the use of selected auxiliary substances. Dry extract from Solidago virgaurea L. was the study material. Shrimp chitosan, silicified microcrystalline cellulose (Prosolv), polyvinylpyrrolidone, calcium carbonate and sodium stearyl fumarate were used as auxiliary substances. Eleven tablet batches were manufactured in a reciprocating instrumented tableting machine (Ewreka). The produced tablets were subjected to morphological tests comprising the tablet size, determination of batching accuracy (determination of mass uniformity of individual tablets), test of mechanical resistance (crushing strength), determination of disintegration time. The statistical hardness of the manufactured tablets was also estimated. Pharmaceutical availability tests were performed of the biologically active substances released from tablets to the acceptor fluid. The study was based on general and detailed regulations of Polish Pharmacopoeia VII (PP VII). The obtained results allow to conclude that the applied auxiliary substances appeared to be useful in adequate proportions in manufacturing tablets containing dry extract from Solidago virgaurea L. The properties of the obtained batches of tablets were in majority consistent with the current requirements. The applied method provides technological reproducibility and high durability of the drug. These tablets as compared to available herbal mixtures and aqueous extracts can be a more comfortable form of a drug.

Topics: Biological Availability; Calcium Carbonate; Cellulose; Chitosan; Drug Compounding; Excipients; Fumarates; Models, Theoretical; Plant Extracts; Solidago; Tablets; Technology, Pharmaceutical

The aim of this study was to evaluate the effect of lubricants on the characteristics of orally disintegrating (OD) tablets manufactured using the phase transition of sugar alcohol. OD tablets were produced by directly compressing a mixture containing lactose-xylitol granules, disintegrant, glidant and lubricant, and subsequent heating. The effect of the type of lubricant on the tablet characteristics was evaluated using magnesium stearate (Mg-St), sodium stearyl fumarate (SSF), and talc as lubricants. The hardness of the tablets increased to ca. 6kp as a result of heating, regardless of the kind of lubricant. The oral disintegration time of the tablets containing Mg-St or SSF increased with an increase in the hardness. In contrast, the oral disintegration time of the tablets containing talc was not changed despite of an increase in hardness. The water absorption rate of the tablets containing talc was much faster than that of the tablets containing other lubricants. The surface free energy measurement showed that the polarity of the tablet components containing talc was remarkably increased by heating. The water absorption rate of the tablets containing talc was also increased by heating. These results indicate that a more hydrophilic surface might be attained by heating the talc. Consequently, talc was demonstrated to be the most desirable lubricant for the preparation of OD tablets based on the principle of the phase transition of sugar alcohol.

Topics: Absorption; Administration, Oral; Chemical Phenomena; Chemistry, Physical; Excipients; Fumarates; Hardness; Lactose; Lubricants; Porosity; Solubility; Stearic Acids; Sugar Alcohols; Surface Properties; Tablets; Talc; Water; Xylitol

The characteristics of various pharmaceutical dosage forms are influenced by surface properties such as the friction behavior. For example, die wall friction is a key issue in developing a solid dosage form. However, the friction properties are not completely understood mainly because of the lack of fundamental measurements. Herein, the friction behavior of pharmaceutical materials was investigated and compared with their adhesion behavior using atomic force microscopy. The sliding speed causes significant variations in the frictional force. Compared with other materials, lubricant materials showed less distinct differences in friction tests than in adhesion tests, indicating the dependence of the lubricant efficiency on the stress state. The three parameters obtained from the modified Amonton's law, i.e., absolute frictional force, friction coefficient and residual force, showed consistent trends. Overall, the friction behavior was not a direct reflection of the adhesion forces. The intrinsic friction behavior of a single pharmaceutical particle can be quantified using atomic force microscopy.

Topics: Acetaminophen; Adhesiveness; Chemistry, Pharmaceutical; Dosage Forms; Drug Compounding; Excipients; Friction; Fumarates; Kinetics; Lactose; Microscopy, Atomic Force; Models, Chemical; Nanotechnology; Stainless Steel; Stearic Acids; Surface Properties; Technology, Pharmaceutical

The paper deals with a study of tensile strength and disintegration time of compacts made from silicified microcrystalline celluloses, Prosolv SMCC 90, and Prosolv HD 90, in dependence on compression force, addition of two types of lubricants, and two active ingredients. The lubricants were magnesium stearate and sodium stearyl fumarate in a concentration of 0.5%, the active ingredients being ascorbic acid and acetylsalicylic acid in a concentration of 50%. Prosolv SMCC 90 proved to be better compatible than Prosolv HD 90; the compacts were of higher strength, which was markedly increased with increasing compression force. Prosolv HD 90 was more sensitive to additions of lubricants, and a greater decrease in strength was recorded due to the influence of sodium stearyl fumarate. The effect of lubricants on the strength of compacts in the presence of active ingredients was not identical. The disintegration time of compacts from Prosolv HD 90 without as well as with lubricants was shorter than from Prosolv SMCC 90 and was increasing with increasing compression force. Disintegration time was increased with added lubricants, and it was markedly shortened by addition of active ingredients. Compacts containing ascorbic acid possessed a shorter disintegration time than those containing acetylsalicylic acid, and it was not markedly influenced by the presence of lubricants.

Topics: Ascorbic Acid; Aspirin; Cellulose; Chemistry, Pharmaceutical; Excipients; Fumarates; Lubrication; Silicon Dioxide; Stearic Acids; Tablets; Technology, Pharmaceutical; Tensile Strength

A method for the determination of sodium stearyl fumarate aqueous suspension is described. This straightforward method is based on homogenisation of the sample, dilution of a known aliquot with methanol to a suitable clear solution and mixing with an internal standard; (S)-naproxen. Separation and quantification is performed by packed column supercritical fluid chromatography on a commercial tartaric acid network polymeric column (tertbutylbenzoyl) with UV-detection at 214 nm. The precision of the presented method upon repeated analysis of a 20 mg/ml suspension is 0.5% (n = 8), and the yield is near 100%. Less than 5 min is required for the chromatographic separation with a resolution of about 3 to the internal standard. With some modification of the chromatographic conditions water samples can also be analysed.

Topics: Chromatography, Supercritical Fluid; Excipients; Fumarates; Methanol; Reproducibility of Results; Spectrophotometry, Ultraviolet; Suspensions; Water