Biomedical subjects

M V Dali

Publications and source records attributed to M V Dali.

3 recordsLinked to original sources

PubMed1998

Particle size distributions from multiparticulate dissolution.

It has been demonstrated theoretically that the particle size distribution of particles in a given sieve fraction of a powder may be assessed by means of short-term dissolution data. Theoretical considerations in this article show that by accounting for polydispersity in a powder sample, the cubic expression in time for amount undissolved and fraction undissolved gives rise to integrals that are essentially moments of the distribution function of one of the defining dimensions of the particle. The first and the second moments can be used to calculate the distribution parameters, (mean and standard deviation) of such a dimension of a crystalline powder. The theory is based on a model geometry, a parallelepiped, for the description of particles such as needles, plates, and prisms. The theory is substantiated by experimental data. A method for obtaining the particle size distribution parameters from the results of dissolution of three sieve fractions of oxalic acid dihydrate, and the general application of this to particle size determination is discussed. To validate the method, the distribution of lengths and breadths of oxalic acid dihydrate particles was obtained from microscopy. From actual powder dissolution data, an estimate of the mean height-to-breadth ratio of these particles belonging to a certain sieve fraction was obtained. With the knowledge of the dissolution rate constant, K, for oxalic acid dihydrate under specified hydrodynamic conditions, it was possible to evaluate the moments of the distribution function. The distribution parameters so obtained were in good agreement with the results obtained from microscopy.

Crystallization↗

PubMed1996

Effect of change in shape factor of a single crystal on its dissolution behavior.

PURPOSE: To study the effect of change in the shape factor of real crystals on their dissolution behavior using a potassium dichromate crystal as a model for particulates in general. METHODS: A model geometry (parallelepiped) has been suggested for a dissolving particle. Single crystals of potassium dichromate which are monoclinic prisms were grown individually from supersaturated solutions at 40 degrees C. Dissolution studies were carried out on five such crystals in 0.1N H2SO4 at 25 degrees C and a stirrer speed of 50 +/- 1 rpm. The five crystals had different degrees of non-isometricity. Initial dimensions of the crystals were measured using image analysis techniques. The shape factor of the dissolving crystal as a function of time was obtained indirectly from the dissolution data. RESULTS: The shape factor of a single crystal changed significantly after about 50% dissolution. The nature of this change depended on the degree of non-isometricity of the crystal. The change in shape factor of the dissolving crystal was accounted for in the Hixson-Crowell cube root law, and a modified form of the cube root equation was developed. This equation for dissolution explained the observed upward curvature in the cube root law plot. CONCLUSIONS: The shape factor for any non-isometric particle cannot be considered to be constant over the dissolution event, as is commonly assumed. This change has an appreciable effect on the dissolution behavior of crystals. This study is particularly of significance for elongated shapes like needles and platelets. By the methodology described here, it was possible to determine the initial shape factor of the crystal and the intrinsic dissolution rate constant.

Crystallization↗

PubMedDate not supplied

Moisture sorption behavior of selected bulking agents used in lyophilized products.

To develop a rational approach for the formulation of lyophilized products, six bulking agents commonly used in freeze-dried formulations were lyophilized under identical conditions, and their moisture sorption behavior, before and after lyophilization, were determined as a function of relative humidity at 25 degrees C. The bulking agents evaluated were mannitol, anhydrous lactose, sucrose, D(+)-trehalose, dextran 40 and povidone (PVP K24). The materials were also characterized for their crystal and thermal properties by powder X-ray diffraction, DSC and TG after exposure to various relative humidity conditions. Mannitol was crystalline and non-hygroscopic both before and after lyophilization with total moisture contents of 0.1 to 0.3% w/w between 10 and 60% RH. Anhydrous lactose, sucrose and trehalose were crystalline prior to lyophilization with moisture contents of 0.86, 0.15 and 9.2%, respectively, and the crystalline materials were relatively non-hygroscopic. Upon lyophilization, they converted to the amorphous form and had moisture contents of 1.6, 2.5 and 1.2%, respectively. The amorphous materials sorbed moisture rapidly upon exposure to increasing relative humidity conditions. The amorphous lactose converted to its crystalline hydrate form at 55% RH after sorption of an additional 10% moisture. This conversion to the crystalline hydrate form was accompanied by desorption of practically all the moisture sorbed by the amorphous form. Similarly, lyophilized sucrose converted to its crystalline form after the sorption of additional 4.5% moisture at 50% RH, and the lyophilized trehalose sorbed additional 10% moisture prior to its conversion to a crystalline hydrate form at 50% RH. Dextran and povidone were amorphous and hygroscopic both before and after lyophilization and they sorbed as much as 10-20% moisture at 50% RH. It is well established that different drugs, especially proteins, need different levels of moisture for optimal stability. The results of the present study show that moisture contents of lyophilized cakes may be varied and optimized by the selection of suitable excipients.

Calorimetry, Differential Scanning↗