Color Stability of Ascorbic Acid Tablets Measured by Tristimulus Colorimeter

Abstract

The influence of three different tableting diluents and three different forms of ascorbic acid on the color change of vitamin C have been investigated. Ten different direct compression formulations were made and subjected to accelerated stability study. Color changes in tablets were monitored with a Tristimulus Colorimeter. It has been found that lactose and Emdex influenced the color change of direct compression ascorbic acid tablets to a lesser degree than Sorbitol. Further, Calcium Ascorbate brought changes in the color of the tablets at a faster rate than C-90 or Sodium Ascorbate. A good correlation of 0.998 was found for a linear relation of visual color rating against normalized total color difference values of these tablets.     

Gamma Sorbitol as a Diluent in Tablets

Abstract

Several crystal structures of Sorbitol may be encountered. Eleven Sorbitol samples from five different manufacturers were studied by X Ray diffraction and differential scanning calorimetry. Three crystalline forms were identified. The γ form is the most stable. One of these samples was constituted by the pure γ form.

Sorbitol is usually considered as a very hygroscopic excipient. We studied this most stable Sorbitol for its technological and biopharmaceutical properties in tablet formulation.

Aspirin and Acid Ascorbic tablets were prepared with γ Sorbitol as a diluent, in high concentration, by direct compression. Three disintegrants were tested: maize starch, Kollidon CL^R, Ac Di Sol^R. Using either lactose or γ Sorbitol as a diluent, different batches of tablets were prepared with the same proportion of diluent and in the same conditions.

Compression properties, hardness, disintegration time, dissolution rate and stability in moist conditions were studied.

The tablets containing γ Sorbitol show:

- a better ratio compression force/hardness

- a longer time of disintegration and dissolution

- the very great importance of the choice of the disintegrant: Ac Di Sol was much better than Kollidon CL or Maïze starch in this case of formulation: conserved during one year at 80% Relative Humidity, tablets with γ Sorbitol and Ac Di Sol kept their aspect and their biopharmaceutical properties very well. A slightly greater acid ascorbic alteration with Sorbitol as a diluent than with lactose can be noticed.

It seems that γ Sorbitol is a stable diluent if the Relative Humidity is lower than 80%. Then it should be avoided with drugs too sensitive to moisture like ascorbic acid.

In spite of a slower release time, its hardening power and its very good compression properties can be of great interest.     

Influence of Storage Under Tropical Conditions on the Stability and Dissolution of Ascorbic Acid Tablets

Ascorbic acid tablets stored at 40°C and 90% R.H. demonstrated substantial changes in chemical as well as physical stability including color, disintegration time, hardness and dissolution rate. Tablets stored at 40°C and 35% R.H. showed virtually no change in chemical stability and hardness but measurable changes in disintegration time and dissolution rate. Moisture appeared to be a significant contributing factor to the enhancement of the chemical and physical instability of ascorbic acid tablets.     

Dissolution properties of direcet compression tablets containing an agglomerated cellulose powder

In previous studies a novel agglomerated cellulose powder was shown to own advantageous properties for direct compression. Due to the favourable particle and powder properties this material has good binding and disintegration ability in direct compression tablets. In this study the dissolution properties of direct compression tablets containing the agglomerated cellulose powder as a fillerbinder were evaluated. Especially the effect of the amount of cellulose, the porosity of tablets, the solubility of drug material and the amount and the amount and mixing method of lubricant, magnesium stearate were studied.

Tablets containing different amounts of cellulose with dicalcium phosphate as a filler and 10 wt % of water soluble sodium tolmetin as a drug were compressed at a constant pressure of 150 MPa. The breaking strength of tablets increased with increasing amounts of agglomerated cellulose powder. However, the dissolution of drug accelerated up to cellulose amount of 50 wt %. This was due to the ability of the agglomerated cellulose powder to enhance the water penetration into powder compact and the loosening of tablet structure, i.e. formation of cracks.

Tablets containing 20 wt % of cellulose material and 10 wt % of drug material were compressed to different porosities. Tablet porosity had no effect on dissolution of poorly water soluble tolfenamic acid. Also the dissolution of water soluble sodium tolmetin was only slightly affected by the porosity of tablets. This supports the suggested disintegrant mechanism of the agglomerated cellulose powder. The expansion of cellulose agglomerates, which have been deformed, under compression, is widely responsible for the disintegration of the tablets. An increase in the amount as well as in the mixing intensity of magncsium stearate decreased the dissolution of sodium tolmetin from tablets containing 20 wt % of agglomerated cellulose. However, the intrinsic wetting and dissolution phenomens were practically unchanged when the amount of magnesium stearate was below 2 wt %. Thus, the retardation of drug dissolution was acceptable at low lubricant concentrations.

The properties of tablets containing the agglomerated cellulose were compared to those containing microcrystalline cellulose. In all cases tablets containing the agglomerated cellulose powder liberated drug clearly faster and more properly than corresponding microcrystalline cellulose tablets.     

Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time,Running Time,and Lubricant Concentration

Abstract

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time, Running Time, and Lubricant Concentration

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

A Study of the Compactibility Characteristics of a Direct Compression and A Wet Granulated Formulation of Norfloxacin

Compaction characteristics of norfloxacin tablets manufactured by both wet granulation and direct compression procedures were studied with the aid of an instrumented single punch tablet press interfaced with a digital computer. Under comparable tabletting conditions, the direct compression formulation required less compressional force than the wet granulated formulation to produce tablets of similar breaking strengths, which indicates superior compactibility. The directly compressed tablets were found to disintegrate faster and release their active component more rapidly during the critical early stages of dissolu-tion. Dissolution and disintegration of the directly compressed tablets generally were less affected by changes in breaking strengths than those compressed from granulated systems.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

Aging of Tablets Prepared by Direct Compression of Bases with Different Moisture Content

Abstract

Properties of aged tablets prepared by the wet granulation method were found to be affected by the moisture content of the granules. In this study, the storage-induced changes in hardness, disintegration and drug release were evaluated for tablets made by direct compression of three different bases with different initial moisture content. Tablets with high initial moisture content were found to increase in hardness upon storage. The magnititude of such increase is dependant upon the physical properties of the base and the absolute moisture content. The increase in hardness may increase the disintegration time and decrease drug release. Tablets with low initial moisture content were minimally affected by storage. The gain of moisture by some of these tablets led to enhancement in disintegration and drug release. Among the tablets studied lactose based tablets with different initial moisture content were found to be the most resistant to changes upon storage.     

Ontrolled-Release Theophylline Tablet Formulations Containing Acrylic Resins. I. Dissolution Properties of Tablets

The dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from Theodur^R (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin.     

Preparation and In-Vitro Evaluation of Powder Solution Tablets of Valproic Acid

Abstract

A tablet dosage form of liquid valproic acid (VPA) was formulated using powder solution technology as an alternative to the manufacturing of soft elastic gelatin capsules (SEGs). Mixing of liquid VPA with suitable adsorbents followed by blending with other excipients resulted in a non-adherent, free flowing powder. Tableting was achieved through standard direct compression. The tablets were acceptable in terms of physical properties. Film coated tablets (FCTs) and sugar coated tablets (SCTs) were also prepared. The in-vitro dissolution rates of these VPA tablets were significantly greater than that of a marketed SEG product. There was no significant change in the dissolution rates of the plain and FCTs after storage under accelerated stability conditions. Powder solution technology was a viable alternative to the commercial preparation of SEGs.     

Ontrolled-Release Theophylline Tablet Formulations Containing Acrylic Resins. I. Dissolution Properties of Tablets

Abstract

The dissolution properties of controlled-release theophylline tablets containing acrylic resins are presented. Four different resins (Eudragit RSPM, RLPM, Sl00 and Ll00) were incorporated into theophylline tablets by direct compression techniques and the properties of the resulting dosage form were evaluated in dilute acid, buffer media pH 4.0 and simulated intestinal media pH 7.5. Tablets (500 mg) containing 300 mg of theophylline were prepared with each of the four resins and compressed to a hardness level of 6.5 to 7.5 kg. Excellent flow properties, weight uniformity and drug content uniformity were observed with all tablet formulations. Preliminary data suggest that three of the four resins tested showed great promise as a retardant in a matrix controlled drug delivery system. The dissolution properties of three commercially available sustained-release theophylline tablets were also determined. A comparison of profiles from Theodur^R (300 mg) in acid and simulated intestinal media showed a similarity in release properties to those of theophylline in tablets containing the RLPM resin.     

Effect of Storage Conditions on The Physical Properties and In Vitro Dissolution of Directly Compressed Tablets

Tablets of aspirin, ascorbic acid and pyridoxine hydrochloride were prepared by direct compression, using bone powder or Emcompress, respectively as direct compression fillers. Tablet properties such as mean weight, thickness, breaking strength and friability were monitored before and after storage for 30 days under specified temperature and relative humidity conditions. The tablet properties were apparently unaffected by the conditions of storage, while release parameters were, however, modified. In vitro dissolution rate constant, was found to exhibit good correlation with the dissolution efficiency.     

Controlled release camptothecin tablets based on pluronic and poly(acrylic acid) copolymer. Effect of fabrication technique on drug stability, tablet structure, and release mode

Poly(ethylene oxide)-b-poly(propylene oxide)-b-(polyethylene oxide)-g-poly(acrylic acid), a graft-comb copolymer of Pluronic 127 and poly(acrylic acid) (Pluronic-PAA), was explored as an excipient for tablet dosage form of camptothecin (CPT). The tablets were prepared by either direct compression of the drug-polymer physical blend, suspension in ethanol followed by evaporation, or compression after kneading and characterized with respect to their physical structures, drug stability, and release behavior. Porosity and water uptake rate were strongly dependent on the fabrication procedure, ranking in the order: direct compression of physical blend > compression after suspension/evaporation in ethanol > compression after kneading. Tablets prepared by compression of physical blends swelled in water with a rapid surface gel layer formation that impeded swelling and disintegration of the tablets core. These tablets were able to sustain the CPT release for a period of time longer than those observed with the tablets made by either suspension/evaporation or kneading, which disintegrated within a few minutes. Despite the tablet disintegration, the CPT release was impeded for at least 6 hr, which was attributed to the ability of the Pluronic-PAA copolymers to form micellar aggregates at the hydrated surface of the particles. Physical mixing did not alter the fraction of CPT being in the pharmaceutically active lactone form, whilst the preparation of the tablets by the other two methods caused a significant reduction in the lactone form content. Tablets prepared from the physical blends demonstrated CPT release rates increasing with the pH due to the PAA ionization leading to the increase in the rate and extent of the tablet swelling. The results obtained demonstrate the potential of the Pluronic-PAA copolymers for the oral administration of chemotherapeutic agents.     

Preparation and Properties of Tablets Prepared from Furosemide-PVP Solid Dispersion Systems

Abstract

Tablets were prepared from the solid dispersion of furosemide: PVP by using different techniques such as direct compression and double compression. The results were compared with similar tablets prepared by physical mixture. Direct compression was much prefered, as it provided tablets with acceptable mechanical and physical qualities. On the other hand, the choice of disintegrant is very important in the formulation of furosemide: PVP solid dispersed tablets. With Kollidon CL, the best result was obtained. Disintegration mechanism of this system was also discussed. The other effective factor is the particle sizes of coprecipitates. Fine particle exhibited compression difficulty. The drug release from these tablets was 17 times greater than that from tablets prepared from physical mixture.     

Stability of Ascorbic Acid-Zinc Sulphate Tablets

Abstract

Microencapsulation using ethylcellulose and embedding in stearic acid or polyethylene glycol 6000 have been employed to protect ascorbic acid from metallic ion catalysed oxidation in tablets containing zinc sulphate. It is observed that presence of Zn in the tablets do not affect stability of ascorbic acid even at accelerated storage conditions provided the moisture content is controlled.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.     

Effect of Storage Conditions on The Physical Properties and In Vitro Dissolution of Directly Compressed Tablets

Abstract

Tablets of aspirin, ascorbic acid and pyridoxine hydrochloride were prepared by direct compression, using bone powder or Emcompress, respectively as direct compression fillers. Tablet properties such as mean weight, thickness, breaking strength and friability were monitored before and after storage for 30 days under specified temperature and relative humidity conditions. The tablet properties were apparently unaffected by the conditions of storage, while release parameters were, however, modified. In vitro dissolution rate constant, was found to exhibit good correlation with the dissolution efficiency.     

Factors Influencing the Release of Aminophylline from Tableted Ethylcellulose Microcapsules

Microcapsules containing aminophylline cores in ethylcellulose walls have been prepared and tableted. The mechanical properties and the release characteristics of tablets obtained by direct compression at six different pressures (ranging from 265 to 1060 Kg.cm^-2) were studied. The release rate of the drug from tableted microcapsules increased with the increase of compression force and was higher than from uncompressed microcapsules, indicating that some damage of the polymeric wall occurred during the compression process. Among the various excipients tested as binding and protective agents, paraffined starch (a mixed system appositely set up) gave the best results, producing the slowest drug release rate. No important effect on drug release rate was found by changing the size of the microcapsules.     

Investigation of Ethylcellulose as a Matrix Former and a New Method to Regard and Evaluate the Compaction Data

Abstract

Three types of ethylcellulose—having different molecular weights, i.e., different viscosity grades (7, 22, 50 cP)-were used for our polymer compression tests for the production of matrix tablets. The production methods used were direct compression and wet granulation. We tested the compactability, the compressibility, and the energy involved in compaction by the use of F-D curves and the controlled drug release from the ethylcellulose matrix tablets using the above-mentioned methods. A lower viscosity grade in ethylcellulose is more compressible than the higher grade. Wet-granulated ethylcellulose also shows a better compactibility than directly compressed ethylcellulose. Our investigation indicates also that the dissolution rates are indirectly proportional to the hardness of the tablets. Furthermore, wet-granulated tablets produce a more rapid drug release than those which are directly compressed.