Effect of Formulation and Process Variables on the Dissolution Profile of Naproxen Sodium from Tablets

Abstract

Results of this investigation revealed some important formulation characteristics of naproxen sodium. Tablets made from the granules, prepared by wet granulation method using water, showed a significant decrease in solution as compared to those made by dry blending method. During wet granulation, heat was evolved due to the hydration of naproxen sodium resulting in the retardation of dissolution. The pseudo-polymorphism and hydration is being investigated by Bansal et. al. (1). In addition, when polyvinyl pyrolidone (PVP K-90) was used instead of PVP K-30, the dissolution was further retarted. Addition of cross carmellose sodium (Ac-Di-Sol) did not change the dissolution behavior of these tablets. When naproxen sodium was granulated with water, a decrease in dissolution rate was observed as mixing time was increased from 5 minutes to 15 minutes. The increase in hardness of the tablet from 10 Kp to 18Kp did not alter the dissolution profile of naproxen sodium. When granulation was prepared using a low shear mixer (Planetary mixer) versus a high shear mixer (T.K. Fielder), the resultant tablets exhibited similar dissolution and physical chemical properties.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

Abstract

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

Effect of Formulation Variables on Dissolution Profile of Diclofenac Sodium from Ethyl- and Hydroxypropylmethyl Cellulose Tablets

The effects of formulation variables on the release profile of diclofenac sodium from ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC) matrix tablets were investigated. With increase in viscosity of ethyl cellulose used in nonaqueous granulation, a decrease in drug release from the tablets was observed, while the percentage of fines articles passed through 60 mesh) in the granulation had a significant effect on the dissolution profile. Granules containing 15% fines exhibited slow release of the drug in comparison to those containing 30% fines with EC matrices. An analysis of kinetics of drug release from hydrophobic EC matrix showed Fickian diffusion regulated dissolution. Drug release from HPMC tablets followed an apparent zero-order kinetics.     

The Influence of Formulation on the Dissolution Profile of Diclofenac Sodium Tablets

ABSTRACT

In attempts to design delayed-release tablets of diclofenac sodium, seven experimental batches were produced. The influence of super-disintegrant croscarmellose sodium (CCS), the granulation process, and the thickness of Eudragit® L 100 coating film were evaluated. The values of dissolution efficiency and the similarity factor were used to compare the dissolution profiles of each experimental batch and the reference Voltaren®. Both methods appear to be applicable and useful in comparing dissolution profiles. Based on such values four batches were considered similar when contrasted with the reference. The results suggest an optimal relationship between the amount of CCS and the thickness of the coating film, which provides appropriate dissolution rate of diclofenac sodium from the dosage forms.     

The Effect of Formulation on 1-131 Dissolution In Vitro from Sodium Iodide Capsules

Because of the importance of the bioavailability of 1-131 for thyroid uptake studies and thyroid therapy, the present investigation was conducted to determine the influence of diluents, type of lubricant and the concentration of lubricant on the in vitro release rate of 1-131 from 1-131 sodium iodide capsules. Formulations and 1-131 sodium iodide capsules were prepared in-house and dissolution profiles determined using the U.S.P. XXII Dissolution Test. Distilled water was employed as the solvent. Lactose only, calcium phosphate only, a mixture of dicalcium phosphate—Avicel PH 101 and a sodium phosphate formulation consisting of lactose, L-cysteine hydrochloride and sodium phosphate were chosen as diluents. Several concentrations of the lubricant magnesium stearate were employed. The influence of 3% or 5% talc as the lubricant was studied using the sodium phosphate formulation.

The results of the study demonstrated the influence of the formulation on the dissolution of 1-131 when the concentration of magnesium stearate was held constant. This was particularly noted at a 3% concentration and to a lesser degree at a 1% concentration of magnesium stearate. The dissolution rate for 1-131 from capsules prepared with the sodium phosphate—Avicel PH 101 formulation was slow and not influenced by varying the concentration of magnesium stearate. Using talc as the lubricant resulted in 1-131 dissolution rates that were rapid for the sodium phosphate formulation. Based upon the findings it is apparent that the diluent and the lubricant can influence the dissolution rate of 1-131 from sodium iodide labeled capsules. The relationship of in vitro dissolution profiles should be compared to the bioavailability of 1-131 in animals to ascertain the importance of formulation in thyroid function studies and treatment.     

The Dissolution of Verapamil from Tablets Prepared with two Sodium Polyphosphates

Abstract

The ratio of the two polyphosphates, soluble sodium polyphosphate (SPP) and insoluble Maddrell's Phosphate (MPI), will influence the release rate of verapamil from tablets and compressed discs. Dose forms which contain only MPI release the drug constantly for about 8 hours and the inclusion of SPP tends to increase the release rate. Although the tablets containing verapamil and the polyphosphate mixture are harder than similar tablets without the drug, the hardness of the tablets is not influenced by the ratio of the polyphosphates employed and does not cause the variation in release rate observed.     

The Dissolution of Verapamil from Tablets Prepared with two Sodium Polyphosphates

The ratio of the two polyphosphates, soluble sodium polyphosphate (SPP) and insoluble Maddrell's Phosphate (MPI), will influence the release rate of verapamil from tablets and compressed discs. Dose forms which contain only MPI release the drug constantly for about 8 hours and the inclusion of SPP tends to increase the release rate. Although the tablets containing verapamil and the polyphosphate mixture are harder than similar tablets without the drug, the hardness of the tablets is not influenced by the ratio of the polyphosphates employed and does not cause the variation in release rate observed.     

Effect of Excipient and Processing Variables on Adhesive Properties and Release Profile of Pentoxifylline From Mucoadhesive Tablets

ABSTRACT

The bioavailability and onset of action of drugs with high first-pass metabolism can be significantly improved by administration via the sublingual route. The objective of this study was to evaluate the effect of polymer type and tablet compaction parameters on the adhesive properties and drug release profile from mucoadhesive sublingual tablet formulations. Pentoxifylline was selected as the model drug because it has poor oral bioavailability due to extensive first-pass metabolism. Two polymers known to possess mucoadhesive properties, carbomer and hydroxypropyl methyl cellulose (HPMC), were used to prepare the formulations. Tablets were prepared by using direct compression technique and evaluated for in vitro dissolution, drug-excipient interactions, and adhesive properties. In general, there was a decrease in the rate of drug release with an increase in the concentration of polymers. No drug-excipient interactions were evident from differential scanning calorimetry or high-performance liquid chromatography analysis. For the formulations containing HPMC, the force of mucoadhesion increased with an increase in the concentration of polymer; however, for carbomer formulations, no such correlation was observed. Force of mucoadhesion decreased as a function of hydration time in both of the polymers.     

Instrumented Tablet Press Studies on the Effect of Some Formulation and Processing Variables on the Compaction Process

Using an instrumented tablet press, compression force-time measurements were used to evaluate the effects of formulation and processing variables on the compaction process. The effects of tablet press speed, punch size, depth of upper punch penetration (into the die), and the setting of the overload spring mechanism were studied. The effects of tablet weight, particle size and amount of lubrication were also studied. Several direct compression materials which are believed to compact by different mechanisms were used in the study. The results indicate the sensitivity of the area under the compression force-time curve and the Area/Height ratio. Some of the changes seen in the area and A/H ratio were those which would be expected from a relatively simple model of compaction/compression. The results clearly show the usefulness of the instrumented tablet press as an analytical tool in the development of tablet formulations, the evaluation of processing requirements, and the remedy of tablet production problems.     

Effects of Process Variables and Excipients on Tabletting Parameters of Norfloxacin Tablets

A study was conducted to evaluate the tabletting parameters of Norfloxacin (NIX) tablets. The effects of method of tabletting. e.g., direct compression, dry granulation and wet granulation, moisture content and water soluble/insoluble additives on final hardness, disintegration and dissolution of the tablets were investigated.     

Effects of Process Variables and Excipients on Tabletting Parameters of Norfloxacin Tablets

Abstract

A study was conducted to evaluate the tabletting parameters of Norfloxacin (NIX) tablets. The effects of method of tabletting. e.g., direct compression, dry granulation and wet granulation, moisture content and water soluble/insoluble additives on final hardness, disintegration and dissolution of the tablets were investigated.     

Effect of Aging on the Dissolution Rate of Nalidixic Acid Tablets

Investigation of the dissolution rate profiles of nalidixic acid tablets of three commercial brands was carried out. Using the U.S.P. paddle method, significant inter-brand variations in dissolution rates were found and the tablets did not pass the U.S.P. dissolution test. The dissolution of the tablets was also found to be adversely affected on aging. The observed differences in dissolution rates of the tablets examined were unrelated to their disintegration times. An attempt was made to improve the dissolution rate of nalidixic acid tablets through hydrophilization of nalidixic acid powder and use of tablet excipients with high aqueous solubility were found to yield tablets of good physical qualities which were unaffected on aging.     

Effect of Aging on the Dissolution Rate of Nalidixic Acid Tablets

Abstract

Investigation of the dissolution rate profiles of nalidixic acid tablets of three commercial brands was carried out. Using the U.S.P. paddle method, significant inter-brand variations in dissolution rates were found and the tablets did not pass the U.S.P. dissolution test. The dissolution of the tablets was also found to be adversely affected on aging. The observed differences in dissolution rates of the tablets examined were unrelated to their disintegration times. An attempt was made to improve the dissolution rate of nalidixic acid tablets through hydrophilization of nalidixic acid powder and use of tablet excipients with high aqueous solubility were found to yield tablets of good physical qualities which were unaffected on aging.     

Effect of Scaling-Up and Formulation Factors on the Qualities of Prednisone Tablets

Four different tablet manufacturing techniques were scaled-up from a bench scale to a semi-large scale in order to study the effect of scaling-up on weight variation and content uniformity of prednisone tablets. One method was further scaled-up to a production scale, and the tablets obtained were tested for content uniformity. The effect of binders and lubricants on tablet hardness, disintegration, dissolution and chemical stability was investigated. It is shown that scaling-up of some techniques affect content uniformity of tablets. The various tablet parameters have been also found to be influenced by the type of binder and lubricant used and by aging of the tablets at normal and accelerated conditions. The presence or absence of intragranular starch as disintegrant appears to affect some of the tablet qualities.     

Effect of Pressure on Disintegration of Tablets and Dissolution of Ephedrine Sulfate

Abstract

The influence of applied pressure on the disintegration of model ephedrine sulfate tablets and the release of ephedrine sulfate is reported. Six frequently used disintegrating agents were employed with a water-soluble diluent (lactose) and with a water-insoluble diluent (dibasic calcium phosphate). Although disintegration time may be independent of pressure (dibasic calcium phosphate) or may be lengthened by increased pressures (lactose), changes in applied pressures did not significantly alter the dissolution of the water-soluble medicinal compound.     

Effect of Pressure on Disintegration of Tablets and Dissolution of Ephedrine Sulfate

The influence of applied pressure on the disintegration of model ephedrine sulfate tablets and the release of ephedrine sulfate is reported. Six frequently used disintegrating agents were employed with a water-soluble diluent (lactose) and with a water-insoluble diluent (dibasic calcium phosphate). Although disintegration time may be independent of pressure (dibasic calcium phosphate) or may be lengthened by increased pressures (lactose), changes in applied pressures did not significantly alter the dissolution of the water-soluble medicinal compound.     

The Effect of Hygroscopic Formulation Ingredients on the Sorption Characteristics of Tablets

In order to examine the effect of hygroscopic ingredients on the sorption characteristics of tablets, three hygroscopic additives - citric acid anhydrous (CAA), sorbitol (SI) and maltodextrin (MA) - were added at concentrations of 10% and 20% to a standard tablet granulate formulation prepared with three different initial moisture contents. The additives chosen were intended to be representative of a range of active ingredients with varying hygroscopicity characteristics.

The granulate/additive mixtures, together with the corresponding additive-free mixtures, were then tabletted, and the sorption isotherms of the resulting tablets were determined. The sorption-related changes in hardness, thickness, diameter and disintegration time were also investigated.

Examination of the sorption isotherms showed that the position of the “ansor-ption point” - the point where the isotherm crosses the x-axis and thus the point at which the tablets start to adsorb water - was much more dependent on the initial moisture content of the tablets than on the presence of a hygroscopic additive. The presence of a hygroscopic additive had little or no effect.

The additives did not begin to have any marked effects on the sorption isotherms of the finished tablets until the relative humidity level reached 62%. Above 62%, however, the differences in the hygroscopicity characteristics of the individual additives had a direct impact on the sorption profiles of the tablets.

As increasing amounts of moisture were adsorbed, tablet hardness fell whilst tablet thickness and diameter increased. The increases in thickness were in all cases greater than the increases in diameter. These findings applied to all tablets irrespective of their initial moisture content.

The sorption-related changes in disintegration time did not exhibit any consistent pattern and have therefore not been interpreted.

A comparison of the areas under the adsorption isotherms yielded the following results:

• The three additives adsorbed differently. Their adsorption, however, was always greater than that of any of the tablet variants.

• The areas under the adsorption isotherms of the additive-containing tablets were in all cases greater than the areas under the adsorption isotherms of the corresponding additive-free tablets. However, the differences were not always directly related to the concentration of the additive or to the area under the adsorption isotherm of that additive.

The relevance of these findings for routine pharmaceutical practice is discussed.     

Relationseips Between Drug Dissolution Profile and Gelling Agent Viscosity in Tablets Prepared with Hydroxypropylmethylcellulose (HPMC) and Sodium Carboxymethylcellulose (NaCMC) Mixtures

Abstract

Two varieties of HPMC, two varieties of NaCMC and various HPMC/NaCMC mixtures were characterized with the aim of providing a sound basis for the selection of appropriate mixtures to use as gelling agents in controlled-release tablets for hydrosoluble drugs. For both HPMC and NaCMC, one variety was of high and the other of low nominal viscosity. We also investigated possible relationships between the rheological properties of HPMC/NaCMC mixtures and atenolol release from tablets prepared with such mixtures. The mean molecular weights of each polymer variety were estimated on the basis of determination of their intrinsic viscosities in aqueous dispersions. Rotational viscosimetry of 2% aqueous dispersions of the polymers and polymer mixtures revealed rheological synergism in some mixtures. Drug dissolution trials were carried out in water and 0.1 N HCl. Dissolution medium, gelling agent composition and proportion of gelling agent in the tablet all affected dissolution profiles. Fitting of Korsmeyer et al.'s equation to the data for dissolution in water indicated zero-order dissolution kinetics for all formulations. For tablets prepared with the most viscous HPMC variety, %hour dissolution efficiency was closely correlated with the apparent viscosity (shear rate 0.5 s^?1) of the aqueous dispersion of the polymer mixture used as gelling agent. Assays of tablet erosion rates indicated that the erosion mechanism may contribute to the observed zero-order dissolution kinetics, but that other factors are probably also involved.     

Relationseips Between Drug Dissolution Profile and Gelling Agent Viscosity in Tablets Prepared with Hydroxypropylmethylcellulose (HPMC) and Sodium Carboxymethylcellulose (NaCMC) Mixtures

Two varieties of HPMC, two varieties of NaCMC and various HPMC/NaCMC mixtures were characterized with the aim of providing a sound basis for the selection of appropriate mixtures to use as gelling agents in controlled-release tablets for hydrosoluble drugs. For both HPMC and NaCMC, one variety was of high and the other of low nominal viscosity. We also investigated possible relationships between the rheological properties of HPMC/NaCMC mixtures and atenolol release from tablets prepared with such mixtures. The mean molecular weights of each polymer variety were estimated on the basis of determination of their intrinsic viscosities in aqueous dispersions. Rotational viscosimetry of 2% aqueous dispersions of the polymers and polymer mixtures revealed rheological synergism in some mixtures. Drug dissolution trials were carried out in water and 0.1 N HCl. Dissolution medium, gelling agent composition and proportion of gelling agent in the tablet all affected dissolution profiles. Fitting of Korsmeyer et al.'s equation to the data for dissolution in water indicated zero-order dissolution kinetics for all formulations. For tablets prepared with the most viscous HPMC variety, %hour dissolution efficiency was closely correlated with the apparent viscosity (shear rate 0.5 s^-1) of the aqueous dispersion of the polymer mixture used as gelling agent. Assays of tablet erosion rates indicated that the erosion mechanism may contribute to the observed zero-order dissolution kinetics, but that other factors are probably also involved.     

The Effect of Processing Variables on the Release of Ibuprofen and Caffeine from Controlled-Release Nonswellable Core-in-Cup Compressed Tablets

An aqueous soluble polymer such as hydroxypropyl methylcellulose (HPMC), which is widely used in oral sustained-release drug delivery systems, swells when it comes into contact with an aqueous environment. In core-in-cup systems the swelling of the HPMC splits open the cup portion of the tablet. This study investigated the use of acacia, tragacanth, polyethylene glycol 6000 (PEG 6000), and hydroxyethyl-cellulose (HEC) as possible alternatives to the use of HPMC to control the release of caffeine (soluble) and ibuprofen (insoluble) from core-in-cup compressed tablets. It also investigated the possibility of producing a core-in-cup system that had the ability to release caffeine and ibuprofen for a maximum time of constant release of 8-12 hr. A preliminary study revealed that acacia was most effective for the release of caffeine from the core-in-cup compressed tablets, and that PEG 6000 was most effective for the release of ibuprofen from the core-in-cup compressed tablets. On further investigation it was found that by means of adjusting the hardness of compression and the concentration of polymers used, it was possible to formulate a core-in-cup system that could release drug at a constant rate from the core-in-cup compressed tablets for 8 to 12 hr.