Addition Of Magnesium Stearate Research Articles

Formulation & Evaluation of Effervescent Tablet of Verapamil Hydrochloride

The chief aim of the present investigation is to study the Formulation & Evaluation of Effervescent Tablet of Verapamil Hydrochloride. The floating tablets of verapamil hydrochloride were prepared by direct compression technique. For each tablet formulation, drug, HPMC-K15M, karaya gum, sodium bicarbonate, and diluents were blended homogeneously for 10 min followed by addition of magnesium stearate. The total weight of each tablet was 300 mg. The amount of karaya gum used was in the range of 40–90 mg, whereas HPMC was used in the range of 20-40 mg. The powder mixture was further mixed for 5 min in a mortar. The resultant mixture was compressed into tablets using a Rimek rotary tablet machine. After preparation, the formulations were evaluated by various parameters. The friability of the tablet formulation varied between 0.3 ± 0.0063 to 0.59 ± 0.0076%. The weight variation of prepared tablet formulation complies with USP limits. The thickness was found to be in the range of 4.1 ± 0.48 to 4.2 ± 0.76 mm. The assay for drug content varied between 96.53 ± 0.36 to 102.03 ± 0.52%. The B1, B5, B6, B9, and B10 exhibited more than 75% drug release at 12 h. The B1 exhibited a maximum of 30 % drug release in the 1st hour and constant release for almost up to 12 h. B8 showed the least drug release among all other formulations; this may be due to the formation of a thick gel barrier on the tablet. Tablets were prepared by direct compression. Technological characteristics of floating tablets were within the Pharmacopoeial limit. Tablets floated for more than 8 h. Complete swelling was achieved by the end of 8 h, so percent swelling was determined at the end of 8 h for all the developed formulations.

Quantification of Fragmentation of Pharmaceutical Materials After Tableting

Deformation is the material property that is a key for successful tablet formulation. Still, a quantitative method for assessing the change in particle size as a result of compression is lacking. The purpose of this study is to introduce a method for quantifying fragmentation after tableting. Different size fractions of dibasic calcium phosphate, microcrystalline cellulose, lactose, and starch were blended with magnesium stearate and compressed into tablets. The compressed particles were recovered from the tablets by manual grinding, which was possible by the addition of magnesium stearate. The recovered particles were subjected to scanning electron microscopy and particle size distribution (PSD) analysis. Fragmentation was quantified by characterizing the change in PSD. PSDs of the compressed samples with increasing compression pressures were analyzed, and more specifically, the particle sizes from the inflection point were used to generate a fragmentation profile. The fragmentation profiles of dibasic calcium phosphate and lactose showed extensive fragmentation during tableting; microcrystalline cellulose fragmented slightly, whereas starch did not fragment at all. The results furthermore showed that the mechanical strength of the tablet was highly dependent on fragmentation, as the mechanical strength did not start to increase before almost all fragmentation had occurred. Hence, by using this method, it is possible to quantify at which compression pressure and to which degree materials fragment during the tableting process.

Development of a New Punch Head Shape to Replicate Scale-Up Issues on a Laboratory Tablet Press III: Replicating Sticking Phenomenon Using the SAS Punch and Evaluation by Checking the Tablet Surface Using 3-D Laser Scanning Microscope

Sticking is a common observation in the scale-up stage on the punch tip using a commercial tableting machine. The difference in the total compression time between a laboratory tableting machine and a commercial one is considered one of the main root causes of scale-up issues in the tableting processes. The proposed “Size Adjusted for Scale-up punch” can be used to adjust the consolidation and dwell times for commercial tableting machine. As a result, the sticking phenomenon is able to be replicated at the pilot scale stage. As reported in this article, the quantification of sticking was done using a 3-D laser scanning microscope to check the tablet surface. It was shown that the sticking area decreased with the addition of magnesium stearate in the formulation, but the sticking depth was not affected by the additional amount of magnesium stearate. It is proposed that the use of a 3-D laser scanning microscope can be applied to evaluate sticking as a process analytical technology tool, and so sticking can be monitored continuously without stopping the machine.

The influence of additives on the in vitro release of drugs from hard gelatin capsules.

Abstract A factorially designed experiment has been used to assess the total percentage of drug released from hard gelatin capsules in vitro as a function of (a) the drug—the drugs being nitrofurantoin, nitrofurazone, oxytetracycline dihydrate and tetracycline hydrochloride; (b) the diluent—the diluents being lactose, Primojel and Dry-Flow starch; (c) the quantity of diluent, either 20 or 80%; (d) the presence (at a 1 % level) and absence of magnesium stearate and (e) the presence (at a 1 % level) and absence of sodium lauryl sulphate. Treatment of the results by analysis of variance, in 5,4, 3 and 2 factor combinations, indicates that the influence of a given factor is often dependent on the other factors. These interdependencies take the form of either a variation in the extent of an effect or the reversal of an effect. The influence of drug and level of diluent show interdependencies of the former kind. Hence, whilst the overall average for drug release indicates that the drugs can be ranked in the ascending order: nitrofurantoin < nitrofurazone < oxytetracycline < tetracycline, the interactions predict that the quantitative ratios of 1:1·8:2·7:5·1 for the drugs above will vary when an additive is present and according to the additive. The rank order will, however, remain unchanged. Similarly, the higher level of diluent will usually increase drug release but not by a constant ratio between drugs. A reversal of an effect is shown by the addition of magnesium stearate, which in some instances increases rather than decreases drug release (its more usual effect). The addition of 1 % sodium lauryl sulphate does not provide a major enhancement of drug release, and in certain cases can be detrimental. There is no consistent order of effectiveness of the three diluents, and thus a universal capsule diluent, which will always improve drug release, does not appear to be a possibility.

A study of the compaction process and the properties of tablets made of a new co-processed starch excipient

This article deals with the study of the energetic relationships during compaction and the properties of tablets produced from a co-processed excipient based on starch and called StarCap1500®. This article compares it with the substance Starch1500®. The study also includes the mixtures of StarCap 1500® and the granulated directly compressible lactose Pharmatose DCL®15. The tablet properties tested included tensile strength and disintegration time, examined in dependence on compression force, and also a 0.4% addition of magnesium stearate. The results show a better compressibility of StarCap 1500 in comparison with Starch 1500 and a lower elastic component of energy. The tablets were stronger and disintegrated more rapidly, but the substance possessed a higher sensitivity to an addition of a lubricant than Starch 1500. Increasing portions of StarCap 1500 in the mixtures with Pharmatose DCL 15 increased the tensile strength of tablets, disintegration period as well as the sensitivity to an addition of a lubricant. From the energetic viewpoint, energy for friction was decreasing, while the energy accumulated by the tablet during compaction and the elastic component of energy were increased.

Study the effect of formulation variables in the development of timed-release press-coated tablets by Taguchi design

In this investigation, the effect of formulation variables on the release properties of timed- release press-coated tablets was studied using the Taguchi method of experimental design. Formulations were prepared based on Taguchi orthogonal array design with different types of hydrophilic polymers (X1), varying hydrophilic polymer/ethyl cellulose ratio (X2), and addition of magnesium stearate (X3) as independent variables. The design was quantitatively evalu-ated by best fit mathematical model. The results from the statistical analysis revealed that factor X1, X3 and interaction factors between X1X2 and X1X3 were found to be significant on the re-sponse lag time (Y1), where as only factor X1 was found to be significant on the response percent drug release at 8 hrs (Y2). A numerical optimization technique by desirability function was used to optimize the response variables, each having a different target. Based on the re-sults of optimization study, HPC was identified as the most suitable hydrophilic polymer and incorporation of hydrophobic agent magnesium stearate, could significantly improve the lag time of the timed-release press-coated tablet.

Magnesium stearate increases salbutamol sulphate dispersion: What is the mechanism?

The objective was to understand the mechanism of enhancement in salbutamol sulphate (SS) respiratory deposition through addition of magnesium stearate (MgSt). The mixing of MgSt with micronized SS occurred using a Turbula mixer (101 rpm), whilst varying mixing time and MgSt concentration and size. Deposition of SS was determined by a twin-stage impinger. Particle size distributions were obtained using the Malvern Mastersizer 2000. Morphology was examined by scanning electron microscopy and surface energy determined using inverse gas chromatography. Mixing of SS with increasing concentrations of MgSt improved dispersion (FPF of 3.3% using 1% w/w MgSt, 4.5% using 5% w/w MgSt and 7.8% using 10% w/w MgSt compared with 1.4% of pure SS for 20 mg doses) when mixed for 0.5 h; SS dispersion improved further after 3.5 h of mixing. In addition to the action of the MgSt in coating SS particles, a greater understanding of the function of MgSt particles in acting as micro-carriers and in changing the mixture structure through incorporation into agglomerates has been achieved. The mechanistic understanding of improvement in drug deposition using MgSt will allow more directed strategies to be employed in designing powder formulations for inhalation.

Assessment of Feasibility of Maillard Reaction between Baclofen and Lactose by Liquid Chromatography and Tandem Mass Spectrometry, Application to Pre Formulation Studies

The aim of this study was to determine any possible, baclofen-lactose Maillard reaction products. Granules and tablets of baclofen and lactose were prepared and maintained in heat ovens for a certain time period. The effects of lactose type, addition of magnesium stearate, and water were monitored. Heated lactose and baclofen were analyzed using reverse-phase HPLC. Liquid chromatography tandem mass spectroscopy revealed nominal mass values consistent with baclofen-lactose, early-stage Maillard reaction condensation products (ESMRP). Multiple reaction monitoring confirmed the presence of ESMRP as well. FTIR analysis proved the formation of imine bond. The results indicated that baclofen undergoes a Maillard-type reaction with lactose.

Particle interaction of lubricated or unlubricated binary mixtures according to their particle size and densification mechanism

The aim of this study is to assess an experimental approach for technological development of a direct compression formulation. A simple formula was considered composed by an active ingredient, a diluent and a lubricant. The active ingredient and diluent were selected as an example according to their typical densification mechanism: the nitrofurantoine, a fragmenting material, and the cellulose microcrystalline (Vivapur), which is a typical visco-elastic material, equally displaying good bind and disintegrant properties. For each ingredient, samples of different particle size distribution were selected. Initially, tabletability of pure materials was studied by a rotary press without magnesium stearate. Vivapur tabletability decreases with increase in particle size. The addition of magnesium stearate as lubricant decreases tabletability of Vivapur of greater particle size, while it kept unmodified that of Vivapur of lower particle size. Differences in tabletability can be related to differences in particle–particle interactions; for Vivapur of higher particle size (Vivapur 200, 102 and 101), the lower surface area develops lower surface available for bonds, while for Vivapur of lower particle size (99 and 105) the greater surface area allows high particle proximity favouring particle cohesivity. Nitrofurantoine shows great differences in compression behaviour according to its particle size distribution. Large crystals show poorer tabletability than fine crystals, further decreased by lubricant addition. The large crystals poor tabletability is due to their poor compactibility, in spite of high compressibility and plastic intrinsic deformability; in fact, in spite of the high densification tendency, the nature of the involved bonds is very weak. Nitrofurantoine samples were then mixed with Vivapurs in different proportions. Compression behaviour of binary mixes (tabletability and compressibility) was then evaluated according to diluents proportion in the mixes. The mix of either nitrofurantoine large crystals or fine crystals with cellulose microcrystalline showed a negative interaction in all proportions, whatever particle sizes. The lubricant addition induced a positive interaction with Vivapur of greater particle size distribution (200, 102 and 101) favouring higher particle adhesivity, while it maintained unaltered that of Vivapurs of lower particle size (105 and 99). Definitely, when cohesive forces are predominant (Vivapur 105 and 99), the establishment of adhesive bonds between nitrofurantoine and Vivapur remain unnoticed; on the contrary, when cohesion bonds between microcrystalline cellulose particles are weakened by the presence of magnesium stearate, the existence of adhesion bonds between particles of different nature is in evidence, leading to a positive interaction.

Effect of Formulation Variables on the Floating Properties of Gastric Floating Drug Delivery System

ABSTRACTPurpose. To evaluate the contribution of formulation variables on the floating properties of a gastric floating drug delivery system (GFDDS) using a continuous floating monitoring system and statistical experimental design. Methods. A modified continuous floating monitoring system, which consisted of an electric balance interfacing with a PC, was designed to perform the continuous monitoring of floating kinetics of GFDDS. Several formulation variables, such as different types of hydroxypropyl methylcellulose (HPMC), varying HPMC/Carbopol ratio, and addition of magnesium stearate, were evaluated using Taguchi design, and the effects of these variables were subjected to statistical analysis. Results. The continuous floating monitoring system developed was validated, using capsules with different density, and a good correlation between theoretical and experimental values was obtained (R2 = 0.9998), indicating the validity of the setup. The statistical analysis indicated that magnesium stearate had a significant effect on the floating property of GFDDS (p<0.05), and addition of magnesium stearate could significantly improve the floating capacity of the GFDDS. It was found that the HPMC of higher viscosity grade generally exhibited a greater floating capacity, but the effect was not statistically significant. For polymers with the same viscosity, i.e., K4M and E4M, the degree of substitution of the function group did not show any significant contribution. A better floating behavior was achieved at higher HPMC/Carbopol ratio. Carbopol appeared to have a negative effect on the floating behavior of GFDDS. Conclusions. It was concluded that by using a validated continuous floating monitoring system, the effect of formulation variables on the floating property of the delivery system and their ranges could be identified. Incorporation of hydrophobic agents, such as magnesium stearate, could significantly improve the floating capacity of the GFDDS.

Preparation of MFP Microspheres Using Polyacrylate Resins for the Therapy of Osteoporosis

Disodium Monofluorophoshate (MFP), a highly water soluble drug, was incorporated in polyacrylate resin microspheres by using the solvent-evaporation technique. The process is based on dispersing the acetone solution of the drug and the polymer in liquid paraffin. Eudragit RS 100/S 100 in a 3:1 ratio turned out as the best coating material. The influence of the main manufacturing factors, namely polymer-drug ratio, addition of magnesium stearate, size of the beads, production temperature and speed of stirring, on the technological characteristics of the microspheres, like release rate of the drug, shape, drug-loading and size of the particle were investigated. The findings resulted in a formulation, which obtains the desired controlled release of the drug in a convenient oral system.

Development of matrix-based theophylline sustained-release microtablets.

Microtablets containing high theophylline content (from 60% to 80%) based on a Eudragit RS PO matrix were produced on a rotary tablet press. The influence of the compaction pressure, the plasticizer content used for the granulation of theophylline particles, and the amount of theophylline on the drug release were investigated. The effects of surface area and the addition of magnesium stearate as a hydrophobic agent on the drug release were studied. The storage stabilities of the release rate at room temperature and at 50 degrees C were also determined. Dissolution profiles expressed as percentage of theophylline dissolved were obtained over 8 hr in 900 ml of purified water at 37 degrees C and 75 rpm. It was observed that the compaction pressure (from 200 MPa to 250 MPa) had no effect on the theophylline release. The use of triethyl citrate (TEC) as a plasticizer in the granulation of theophylline enhanced the physical properties of the microtablets. Theophylline content in the range 60% to 80% did not affect the drug release. The theophylline release obtained was a function of the quotient surface area/tablet weight and therefore was dependent on the tablet diameter. To reduce the dissolution rates, magnesium stearate was added in a concentration up to 50% of the matrix material. Tablets of this hydrophobic formulation fulfilled the requirements of USP 23 for theophylline sustained-release preparations. Storage at room temperature for 3 months and at 50 degrees C for 2 months showed no significant influence on the theophylline release.

Evaluation of Vitacel M80K as a new direct compressible vehicle

Vitacel M80K, a cellulose powder coated with 2% colloidal silica, is a recently developed direct compressible vehicle (DCV). The aim of this study is to investigate the performance of M80K, in comparison with: a laboratory prepared vehicle (ELC +) consisting of a mixture of Elcema P050 (ELC) and 2% Aerosil, and a microcrystalline cellulose (MCC), Avicel PH 101 (Avicel). Bulk density, flow and surface characteristics of the DCVs were determined. Tablets were prepared by direct compression using various drugs; ascorbic acid (fine and coarse crystals), cimetidine, and paracetamol. Tablets prepared with M80K showed less weight variation than those prepared with Avicel. Ascorbic acid-Avicel tablets were slightly harder than those with M80K. However, in the presence of either cimetidine or paracetamol, M80K resulted in the production of tablets with maximum hardness. In most cases, except with paracetamol, M80K produced tablets with slightly higher friability in comparison to Avicel, while ELC + showed maximum friability. M80K-paracetamol tablets showed the minimum friability values and highest hardness sensitivity towards increase of the applied compression force between 5 and 35 kN. M80K-containing formulations showed better hardness tolerance upon the addition of magnesium stearate. Disintegration times for most tablets were relatively short (<5 min).

Compression characteristics of granulated materials. VII. The effect of intragranular binder distribution on the compatibility of some lactose granulations.

Two sets of lactose-polyvinylpyrrolidone granulations (95:5) of different intragranular binder distributions were produced. The intragranular binder distribution was controlled by a two-step granulation procedure. The compactibility as well as the volume reduction behavior of the granulations was evaluated. Granulations with a more homogeneous distribution of binder in the granules generally produced tablets of a higher mechanical strength than granulations with a peripheral localization of binder. The tablet strength of the latter granulations was also comparatively more reduced by the addition of magnesium stearate. Thus, it is suggested that high granule porosity in combination with homogeneous intragranular binder distribution is advantageous for the compactibility of a granulation. The results of this study therefore contradict earlier suggestions in the literature regarding the preferred intragranular binder distribution.

Effects of tableting procedures on the preferred orientation of crystalline particles.

The effects of tableting procedures on the preferred orientation of phenacetin and aspirin crystals in a tablet were investigated. Among aspects of tableting procedures which might affect the preferred crystal orientation, the granulation process, the shape of the punch and the addition of magnesium stearate were investigated. A wet granulation method decreased the mobility of crystals during compression, and thus reduced the degree of preferred orientation. This phenomenon was considered to be one of reasons for the improved lamination properties seen with the granulation method. The shape of the punch affected the preferred orientation ; a concave punch caused a more complex preferred orientation pattern than a flat punch. The preferred orientation was considered to correspond to the stress distribution in a tablet. Magnesium stearate reduced the interparticle friction and facilitated the attainmnet of preferred orientation. The characteristic preferred orientation of crystals in the neighborhood of the upper surface and side surface of a tablet was investigated. The broadest faces of crystals were aligned in parallel to the upper punch face and the die wall.

薬剤粉体の圧縮成形における滑沢剤の影響 塩化カリウム主薬の機械的性質の変化

The compaction behaviours of the potassium chloride powders were studied with or without 2.0% magnesium stearate. Their mechanical properties, namely the stress-strain in the one-dimensional compression, the yield locus and the wall yield locus, were obtained experimentally. The coefficients of internal friction and that of wall friction decreased by addition of magnesium stearate, especially for the latter it was remarkable. Using these data, pressure-transmission-ratios (PL/PU) were calculated theoretically, and compared with experimental results.