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Biomedical subjects

M H Rubinstein

Publications and source records attributed to M H Rubinstein.

At least 19 recordsLinked to original sources

Multiple compression and plasto-elastic behaviour of paracetamol and microcrystalline cellulose mixtures.

Radial tensile strength, friability, ER/PC (elastic recovery/plastic compression) ratio and energy ratio analyses were evaluated for various mixtures of paracetamol and microcrystalline cellulose (Avicel). A good correlation occurred between the energy ratio and the other variables. Linear relationships were found between log tensile strength and percentage energy ratio and also between radial tensile strength and stress relaxation energy. Capping occurred when the percentage energy ratio was greater than 15% and the ER/PC ratio greater than 1.5. To produce tablets with acceptable tensile strength and friability, the percentage energy ratio for Avicel/paracetamol should be greater than 10%. The optimal mixture of the two powders, as far as the tensile strength, friability and absence of capping were concerned, was found to be 50% w/w Avicel, 50% w/w paracetamol.

Acetaminophen

The assay and stability of chlorpropamide in solid dispersion with urea.

Thin layer chromatography followed by reflectance densitometry has been used to evaluate the stability of chlorpropamide-urea during the fusion process. Urea was found to decompose to biuret and chlorpropamide to p-chlorobenzenesulphonamide: several other unidentified decomposition products were detected. The energy for decomposition of chlorpropamide was 57.1 kJmol-1 for melts containing 15 and 30% chlorpropamide. Decomposition followed apparent first order kinetics.

Chlorpropamide

Phase equilibria and stability characteristics of chlorpropamide-urea solid dispersions.

Physical mixtures and melts of various compositions of chlorpropamide and urea have been prepared. The phase diagrams and the effects of ageing of the systems have been measured by differential scanning calorimetry. The eutectic composition was found to contain 89% w/w chlorpropamide. Greater concentrations of chlorpropamide produced solid solutions of urea in chlorpropamide, whereas solid solution formation did not occur at compositions less than 89%. Melts in the range 50-100% chlorpropamide, which included the eutectic, existed as glass solids. The effect of ageing produced generally an increase in the liquidus peak temperature which was considered to be due to a gradual increase in crystal size.

Calorimetry, Differential Scanning

Generated surface area measurement of disintegrating tablets.

The surface areas generated by the disintegration and dissolution of six commercial brands of phenylbutazone tablets B.P. 100 mg have been measured using a Model TA Coulter Counter. The graphs of surface area generated against time were all of the same shape and always reached a maximum value. The initial surface area increase was due to tablet disintegration and deaggregation and followed first order kinetics. A good correlation between the slope of this initial increase and disintegration time was found. The maximum surface area generated correlated at the probability level of better than 99-9% with the dissolution rat measured as t60. The subsequent decrease in surface area, after this maximum, was considered to be due to phenylbutazone dissolution and was also first order rate controlled.

Chemistry, Pharmaceutical

The effect of composition and ageing on the dissolution rates of chlorpropamide-urea solid dispersions.

Discs of chlorpropamide and urea have been prepared by (a) melting and (b) compression. Intrinsic and relative dissolution rates of the discs have been measured and the dissolution process investigated microscopically. Higher dissolution rates were found from melts than from physical mixes. The optimum dissolution rate composition found was for a melt composed of 30% w/w chlorpropamide which possessed an intrinsic dissolution rate 930 times greater than for the pure drug. Sphere formation, during dissolution rate measurement has been observed and a likely mechanism proposed to account for its occurrence. Dissolution rates generally increased with age for most melt compositions.

Chlorpropamide

Granule consolidation during compaction.

The deformation of small cylindrical aggregates of dibasic calcium phosphate was measured during compaction. An analogy between these aggregates and cylindrical granules was proposed. No change in the original shape of the aggregates occurred; the cylindrical shape was maintained even at high compaction pressures. Relaxation of the aggregates occurred at pressures higher than 420 MNm-2 (60.9 x 10(3) lb in.-2) when removed from the compacts, but no relaxation took place at pressures below this value. In addition, the aggregates relaxed by an increase in thickness only; there was no corresponding change in diameter. Up to a pressure of 200 MNm-2 (29.0 x 10(3) lb in.-2), an increase in aggregate diameter occurred, which was accompanied by a reduction in thickness. This change produced only a small reduction in volume, which was attributable to interparticulate slippage resulting in a closer packed arrangement. At a pressure of 200 MNm-2, the aggregate diameter no longer increased because solid bridges were formed between the particles and the die wall, preventing further spreading. From 200 to 420 MNm-2, failure of the material occurred by plastic deformation, which produced only a decrease in aggregate thickness. From 420 to 800 MNm-2 (116.0 x 10(3) lb in.-2), a structure was formed that could support the applied load without further reduction of thickness, and this structure was shown to behave elastically.

Barium

Disaggregation of compressed tablets.

Tablets of dibasic calcium phosphate containing varying proportions of intra- to extragranular maize starch were prepared at three compaction pressures. The surface area generated per tablet after 10 and 30 min of disintegration was measured with an automated counter by a new technique. The optimum starch combination that produced the maximum surface area in a tablet formulation was either 2.5% intra-12.5% extragranular or 15% intragranular starch alone. The distribution of starch did not affect the resultant strength of the tablets, and maximum generation of surface area was achieved by compacting the tablets at as low a pressure as practical.

Chemistry, Pharmaceutical