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Biomedical subjects

Z T Chowhan

Publications and source records attributed to Z T Chowhan.

At least 19 recordsLinked to original sources
PubMed1996

Compaction simulator studies of a new drug substance: effect of particle size and shape, and its binary mixtures with microcrystalline cellulose.

The compaction characteristics of a new drug substance with two crystal habits and particle size fractions as well as its binary mixtures with microcrystalline cellulose were studied using an integrated compaction research system under 300 and 450 MPa pressures. The results indicate that the drug substance has poor intrinsic compaction properties. The three-dimensional hexagonal crystal habit or smaller particle size consistently produced a slightly higher total work of compaction as compared with the cubic brick habit or larger particle size, respectively. However, neither crystal habit produced a coherent compact. The compactability of the drug substance was improved by the inclusion of microcrystalline cellulose, and the crushing strength of the compacts increased as the amount of microcrystalline cellulose in the binary mixture was increased. Such correlation was not observed when the compaction data were evaluated using either the Heckel equation or the percentage porosity change as a function of applied pressure.

Cellulose↗
PubMed1993

Effect of the mode of super disintegrant incorporation on dissolution in wet granulated tablets.

The effect of the mode of super disintegrant incorporation in wet granulated tablets was investigated with three super disintegrants: sodium starch glycolate, crospovidone, and croscarmellose sodium. The disintegrants were incorporated extragranularly or intragranularly or distributed equally between the two phases. Lactose, naproxen, or dibasic calcium phosphate was used as the principal tablet component to provide various degrees of solubility to the formulations. The formulations were dried to three different levels of moisture content. The results indicated that, for the formulations studied, extragranular incorporation resulted in faster dissolution than did equal distribution intragranularly and extragranularly, which in turn was superior to intragranular incorporation. Granulation moisture content was found to have a formulation-specific impact on tablet dissolution, with each main tablet component behaving in a different fashion. When all other factors were kept constant, there was a tendency for croscarmellose sodium to produce faster tablet dissolution than sodium starch glycolate or crospovidone. The super disintegrants tended to promote faster dissolution in a neutral pH medium than in an acidic medium.

Biological Availability↗
PubMed1992

Punch geometry and formulation considerations in reducing tablet friability and their effect on in vitro dissolution.

The tablet friability resulting from formulation variations was studied under controlled granulation moisture content and tablet crushing strength. Tablets made with lactose were more friable than tablets made with microcrystalline cellulose. Replacement of 0.5% magnesium stearate with 0.5% stearic acid in the formula reduced tablet friability, whereas the combination of 0.5% stearic acid and up to 0.25% magnesium stearate did not increase tablet friability, decrease drug dissolution rate, or increase tablet-to-tablet variability in dissolution. Tablets compressed with extra deep concave punches resulted in lower friability compared with tablets compressed with standard concave or deep concave punches. The friabilities of the standard convex and deep convex tablets were similar, indicating that a critical level of punch tip curvature was important in reducing tablet friability. The dissolution rate was not affected by the punch tip geometry, but the tablet-to-tablet dissolution variability at the 0.5% stearic acid level for the extra deep convex tablets was higher compared with the standard convex tablets.

Chemical Phenomena↗
PubMed1991

Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution.

The effect of tablet formulation solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants" (sodium starch glycolate, crospovidone, and croscarmellose sodium) in tablets prepared by wet granulation was investigated. Lactose, calcium phosphate dibasic, sorbitol, and naproxen sodium, alone or in combination, provided varying degrees of solubility and hygroscopicity in the formulations. To monitor in vitro dissolution, 1% p-aminobenzoic acid was added to the formulation as a tracer. The results indicate that highly soluble and/or hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity and solubility of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant.

Calcium Phosphates↗
PubMed1990

Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability.

A computer-optimized experimental design was used to study the effect of incorporating a "super disintegrant", croscarmellose sodium, intragranularly, extragranularly, or distributed equally between the two phases of a tablet in which a poorly soluble drug constituted at least 92.5% of the formulation. The results were analyzed by means of a general quadratic response surface model and suggest that tablets with the same total concentration of super disintegrant dissolve at a faster rate when the super disintegrant is included intragranularly. Tablet friability was not affected by the method of super disintegrant incorporation.

Carboxymethylcellulose Sodium↗
PubMed1990

Drug-excipient incompatibility studies of the dipeptide angiotensin-converting enzyme inhibitor, moexipril hydrochloride: dry powder vs wet granulation.

The drug-excipient incompatibility screen for moexipril hydrochloride (1) using various isothermal stress methods is reported herein. It was found that most of the commonly used filters, disintegrants, lubricants, glidants, and coating agents were incompatible with 1 in dry powder mixtures; moisture and basic (or alkalizing) agents were determined to be the dominant destabilizing factors. In wet granulations, basic agents, however, were found to suppress drug degradation even in the presence of moisture. Supported by the product distribution studies, the stabilization is proposed to involve the neutralization of the acidic drug by the basic excipients.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Effect of tablet solubility and hygroscopicity on disintegrant efficiency in direct compression tablets in terms of dissolution.

The effect of tablet composite solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants", sodium starch glycolate, crospovidone, and croscarmellose sodium, was investigated. Lactose, dicalcium phosphate dihydrate, and sorbitol, alone or in combination, provided varying degrees of solubility and hygroscopicity to the direct compression tablet formulations. To monitor in vitro dissolution, 1% p-aminobenzoic acid was added to the formulation as a tracer. The results indicate that hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant. Composite tablet solubility did not influence the effectiveness of the super disintegrants. Super disintegrants that complied with the same compendial specifications, but were manufactured by different companies, behaved similarly in promoting tablet dissolution.

Chemistry, Pharmaceutical↗
PubMed1986

Drug-excipient interactions resulting from powder mixing. III: Solid state properties and their effect on drug dissolution.

Micronized prednisone was used to study the effect of powder mixing on drug-excipient interactions and their effect on in vitro dissolution from uncompacted, hand-filled capsules. Two powder formulations contained CaHPO4 X 2H2O (dibasic calcium phosphate dihydrate) as a filler and potato starch or sodium starch glycolate as a disintegrant. The third powder formulation contained pregelatinized starch as a disintegrant/filler. The lubricant in these formulations was magnesium stearate. When drug, CaHPO4 X 2H2O, and the disintegrant were thoroughly mixed and hand filled into capsules without compaction, only approximately 70% of the drug dissolved in 30 min. The incomplete dissolution of the drug was caused by the formation of agglomerates and the inclusion of the drug particles by these agglomerates. In contrast, when a mixture of drug and pregelatinized starch was used, complete dissolution of the drug was achieved after 30 min due to the absence of agglomeration and inclusion. Prolonged mixing of the formulation containing CaHPO4 X 2H2O with magnesium stearate resulted in a decrease in the dissolution rate. The total amount of the drug dissolved at the end of 30 min was reduced from 70 to 20%. The decrease in the rate of drug dissolution resulted from drug-excipient interactions which caused flaking of the magnesium stearate particles. The adhesion of these flakes to the drug particles and drug-excipient agglomerates resulted in hydrophobic coating which reduced water penetration. The rate of drug dissolution was not affected when drug and pregelatinized starch were mixed with magnesium stearate for a prolonged time due to the absence of magnesium stearate flaking and film formation.

Capsules↗
PubMed1986

Drug-excipient interactions resulting from powder mixing. IV: Role of lubricants and their effect on in vitro dissolution.

Two lubricants, magnesium stearate and sodium stearyl fumarate, were compared under identical mixing conditions to study their roles in drug-excipient interactions. After prolonged mixing, sodium stearyl fumarate did not interact with the drug or excipients; as a result, the disintegration time and drug dissolution rate from hand-filled, uncompacted capsules were not adversely affected. In contrast, magnesium stearate did exhibit drug-excipient interactions which resulted in lamination and subsequent adhesion of the lubricant to the drug-crospovidone agglomerates. These interactions adversely affected the disintegration time and drug dissolution rate from hand-filled, uncompacted capsules. Although the initial specific surface area of magnesium stearate was higher than that of sodium stearyl fumarate, flaking of magnesium stearate due to particulate-particulate interactions caused a large increase in the surface area. The adhesion of the magnesium stearate flakes to the drug-crospovidone agglomerates resulted in a decrease in the drug dissolution rate.

Chemistry, Pharmaceutical↗
PubMed1983

Effect of intergranular versus intragranular cornstarch on tablet friability and in vitro dissolution.

The effect of blending dry cornstarch versus wet granulation with the drug and other excipients on friability and in vitro dissolution of a ticlopidine hydrochloride tablet formulation was studied. The friability of the tablets was reduced by wet granulating cornstarch with the drug and other excipients compared with the dry blending. The dissolution rate and the tablet-to-tablet variability was improved by incorporating cornstarch in the wet-granulation stage. The lactose placebo tablets, which were wet granulated with either a binder solution or without a binder, also showed reduced tablet friability due to the incorporation of cornstarch in the wet-granulation step. Examination of the tablet cross sections under the scanning electron microscope indicated clumping of starch grains when starch was blended in the dry form. Starch grains were well embedded in the other materials of the tablet and not readily visible when starch was wet granulated with the other excipients. This results in better bonding, fewer weak points, and better homogeneity of the starch disintegrator within the tablet, which accounts for better friability and improved dissolution.

Hardness↗
PubMed1982

Effect of moisture and crushing strength on tablet friability and in vitro dissolution.

The friability and dissolution of a formulation of compressed tablets were studied by varying the granulation moisture and tablet crushing strength. A general quadratic response surface model was used to analyze the data. The response surface contour plots of tablet friability consisted of a series of ellipsoidal curves. The optimum friability corresponding to a granulation moisture content and a tablet crushing strength was a simple minimum. The in vitro dissolution contour plots showed a stationary ridge system. Along the ridge, a large number of combinations of tablet crushing strength and granulation moisture represented 100% drug dissolution. The contour overlays of friability and dissolution contour plots showed a region where both the friability and dissolution requirement could be met. The analysis of the data by means of multiple linear regression was helpful in understanding the role of granulation moisture and tablet crushing strength on tablet friability and in vitro dissolution.

Hardness↗
PubMed1981

Mixing of pharmaceutical solids. II: Evaluation of multicomponent mixing of cohesive powders in cylindrical shear mixer.

The mixing of three organic carboxylic acids with micronized lactose, all cohesive in nature, was studied using a cylindrical shear mixer. Three mixing indexes (s/sigma A, s/sigma R, and the Ashton-Valentin mixing index) were used to evaluate mixing of the three drugs with lactose. The results suggested that maximum homogeneity was reached after 45 min of mixing. However, different mixing indexes showed different sensitivity to homogeneity of the individual components. The mixing index s/sigma A, which is based on setting standard specifications, appears to provide a better evaluation of homogeneity of individual components compared to the mixing indexes based on complete random mixing theory. The latter did not approach unity for any drug component used in this study. These results suggested that mixing of cohesive powders is a complex process and cannot be explained fully by simple theory based on complete random mixing.

Particle Size↗
PubMed1981

Mixing of pharmaceutical solids. III: Multivariate statistical analysis of multicomponent mixing.

The multicomponent mixing for cohesive powders was evaluated by multivariate statistical methods. Tests were carried out for the sampling technique, completely random state and completely segregated state. Hotelling's statistics were not helpful in testing the practical sampling technique. Comparisons of the mixing indexes based on univariate and multivariate statistics indicated excellent consistency in optimizing mixing time. Neither mixing index approached unity because cohesive powders do not reach a completely random state. The multivariate mixing index was smaller than the univariate indexes largely due to interparticular forces among small cohesive particles.

Analysis of Variance↗
PubMed1981

Powder flow studies III: tensile strength, consolidation ratio, flow rate, and capsule-filling-weight variation relationships.

The tensile strength of consolidated powder beds was studied by applying a series of loads to the surface of the powder beds in a tensile tester. The results were plotted as tensile strength versus consolidation pressure. The linearity of these plots suggests a direct relationship between tensile strength and consolidation pressure. The following plots gave linear relationships: (1) tensile strength versus consolidation ratio, (b) tensile strength versus coefficient of variation of the filled weight of the capsules, and (c) logarithm of the tensile strength versus logarithm of the flow rate. These results suggest a direct relationship between tensile strength and consolidation ratio and their usefulness in studying powder flow. The physical significance of the empirical equation used in consolidation studies was explored. A comparison of the empirical equation with a theoretically derived equation, under certain assumptions, suggests that the consolidation ratio is a function of the ratio of the initial volume to the net volume and a function of the coefficient of Rankine. The coefficient of Rankine is a function of the angle of internal friction in the static powder bed.

Capsules↗
PubMed1981

Compression properties of granulations made with binders containing different moisture contents.

The role of the granulation moisture content on compression properties of granules made with selected binders was studied. The results suggested that, at lower pressures, higher moisture-containing granules were slightly more compressible than lower moisture-containing granules. However, at higher pressures, the reverse was true because of the water lubrication effect. At lower moisture levels, the crushing strength of the tablets was dependent on the binder; at higher moisture levels, binder differences became less significant.

Drug Compounding↗
PubMed1980

Role of binders in moisture-induced hardness increase in compressed tablets and its effect on in vitro disintegration and dissolution.

The role of commonly used binders in the moisture-induced hardness increase in compressed tablets containing lactose as a major excipient was studied. Tablets compressed from granulations containing different binders at different moisture levels increased in hardness after overnight exposure to ambient room conditions. The results suggest that this hardness increase is related linearly to the amount of moisture loss from the tablets after compression. The magnitude of the hardness increase is related to the type and concentration of the binder used in wet granulation. The moisture-induced hardness increase in tablets prepared from granulations containing different binders had no effect on the tablet disintegration time and in vitro drug dissolution.

Chemical Phenomena↗
PubMed1980

The effect of low- and high-humidity ageing on the hardness, disintegration time and dissolution rate of dibasic calcium phosphate-based tablets.

The effect of low- and high-humidity ageing on hardness, disintegration time and dissolution rate of dibasic calcium phosphate dihydrate-based tablets prepared at different initial moisture concentrations was studied. Hardness increased while distintegration and dissolution rate decreased on ageing in low humidity. The dissolution rate of tablets containing higher initial moisture was slower than the tablets containing lower initial moisture. On ageing in high humidity, hardness, disintegration and dissolution rates decreased at all initial moistures. The results suggest that the effects of moisture and humidity should be thoroughly investigated for dibasic calcium phosphate dihydrate-based tablets in order to ensure stability and bioavailability of the drug.

Calcium Phosphates↗