PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10959921

Adjusting dissolution specifications for the variability induced by storage conditions.

J M Reynolds·D H Rogers
View original source ↗Export metadata ↓

Abstract

The United States Pharmacopeia requires that drug products meet established dissolution specifications throughout their shelf life. Whereas chemical stability for six months at accelerated storage conditions is generally regarded as providing a two-year expiry period, stress conditions are not considered predictive of dissolution stability at controlled room temperature. This paper presents an application of response surface methodology intended to incorporate the variability induced by storage temperature and relative humidity into robust product dissolution specifications. Contour plots, depicting one-sided tolerance limits of percent released, are presented as a function of crushing strength and dissolution time.

Explore related subjects

Compressive StrengthData Interpretation, StatisticalDrug StabilityDrug StoragePharmaceutical PreparationsSolubilityTabletsTemperatureJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J M Reynolds, D H Rogers. 2000. Adjusting dissolution specifications for the variability induced by storage conditions.. https://doi.org/10.1081/bip-100102504

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2001

The influence of mixing ratio on the toughening mechanisms of a hand-mixed zinc phosphate dental cement.

OBJECTIVE: A range of mixing ratios occur for zinc phosphate cements in clinical usage and trials. The compressive strength of these cements is dependent on mixing ratio and at a critical ratio, a sudden rise in compressive strength is known to occur. This study investigated the mechanisms behind the cement curve behavior in an attempt to explain the strength increase with mixing ratio. METHODS: Crack propagation from indentations produced in cements were examined to identify if any variation in toughening mechanism existed over the range of mixing ratios investigated (1.7-3.2g/ml). Pore distribution within the cylindrical specimens was determined using an image analysis technique. RESULTS: Increasing the powder content from 2.3 to 2.4g/ml increased the number of powder agglomerates formed in the cement mix over individual particles. The likelihood of introducing pores in excess of 42 microm diameter was enhanced when the ratio exceeded 2.6g/ml. SIGNIFICANCE: It is proposed that crack deflection by agglomerates in the cement reduces the energy of the crack fronts emanating from indentations more than would occur with individual powder particles. This decreases the cracks ability to progress and is likely to result in the marked strength increase from 2.3 to 2.4g/ml identified previously. It is suggested that cement pores in excess of 42 microm diameter were probably generated on filling the sample molds with more viscous cements. These results emphasise that the properties of cements manipulated under optimum conditions provide little information on the cement characteristics present in clinical practice.

Compressive Strength↗
PubMed2001

A comparison of the mechanical properties of a gallium-based alloy with a spherical high-copper amalgam.

OBJECTIVES: The aim of the present study was to investigate how the mechanical properties of a palladium free gallium-based alloy (Galloy) compare with a leading spherical high-copper amalgam (Tytin). METHODS: Cylindrical specimens were mechanically condensed, according to the ISO 1559:1986 standard, to measure compressive strength, Vickers hardness, static creep and dimensional change on setting. Disc and beam shaped specimens were manually prepared to assess the diametral tensile and flexural strengths of the investigated alloys. RESULTS: The mean hardness, 1h compressive fracture strength, 24 h diametral tensile and 24h flexural strengths of Galloy were significantly lower (P<0.001) than Tytin. No significant differences in modulus of elasticity, creep, dimensional change on setting, 24 and 168 h compressive fracture strength for the two alloys were identified. SIGNIFICANCE: The significant reduction in the 1 h mean compressive fracture strength and hardness identified for Galloy compared with Tytin possibly indicate a slower setting reaction in the gallium-based alloy. Manual condensation of the gallium-based alloy produced specimens with inferior mechanical properties possibly due to the increased likelihood of introducing voids within the test specimens. Previous reports indicating poor corrosion resistance and moisture sensitivity of gallium-based alloys highlight the need for further research to investigate the effect of the oral environment on the gallium-based alloy.

Compressive Strength↗
PubMed2000

Protein compressibility, dynamics, and pressure.

The relationship between the elastic and dynamic properties of native globular proteins is considered on the basis of a wide set of reported experimental data. The formation of a small cavity, capable of accommodating water, in the protein interior is associated with the elastic deformation, whose contribution to the free energy considerably exceeds the heat motion energy. Mechanically, the protein molecule is a highly nonlinear system. This means that its compressibility sharply decreases upon compression. The mechanical nonlinearity results in the following consequences related to the intramolecular dynamics of proteins: 1) The sign of the electrostriction effect in the protein matrix is opposite that observed in liquids-this is an additional indication that protein behaves like a solid particle. 2) The diffusion of an ion from the solvent to the interior of a protein should depend on pressure nonmonotonically: at low pressure diffusion is suppressed, while at high pressure it is enhanced. Such behavior is expected to display itself in any dynamic process depending on ion diffusion. Qualitative and quantitative expectations ensuing from the mechanical properties are concordant with the available experimental data on hydrogen exchange in native proteins at ambient and high pressure.

Compressive Strength↗