Particle formation size reduction

Some of the current methods of increasing dissolution rates of drugs are particle size reduction, salt formation, and development of the optimized delivery systems, such as solid dispersion, soft gelatin encapsulation, etc. 

Conventional routes to ceramics involve precipitation from solution, drying, size reduction by milling, and fusion. The availability of well-defined mono-dispersed particles in desired sizes is an essential requirement for the formation of advanced ceramics. The relationship between the density of ceramic materials and the sizes and packing of their parent particles has been examined theoretically and modeled experimentally [810]. Colloid and surface chemical methodologies have been developed for the reproducible formation of ceramic particles [809-812]. These methodologies have included (i) controlled precipitation from homogeneous solutions (ii) phase transformation (iii) evaporative deposition and decomposition and (iv) plasma- and laser-induced reactions. 

The influence of various gas pressure conditions within the laser ablation cell on the particle formation process in laser ablation has also been investigated.69 In LA-ICP-MS studies at low pressure (down to 2kPa) a small particle size distribution and a reduction in elemental fractionation effects was obtained. But with decreasing pressure and transport volume of ablated material, a significant decrease in the ion intensities was observed as demonstrated for uranium measurements in the glass SRM NIST 610.69 However, the laser ablation of solid materials at atmospheric pressure in LA-ICP-MS is advantageous for routine measurements due to lower experimental effort and the possibility of fast sample changing in the ablation chamber. Fractionation... 

Particle size reduction involves input of energy that gets disseminated during micronization process, along with formation of smaller particles having new surfaces. With an enormous increase in surface area, the newly formed particles need to be stabilized-fo prevent subsequent agglomeration induced by interparticulate interactions and maintain their existence as individual nanoentities. 

There is evidence to show that the particle size of the filler also plays a significant role in flammability resistance. For example, below a certain particle size (about 1-2 pm), in many tests, including oxygen index, aluminum hydroxide shows enhanced fire-retarding performance,34 which may be associated with the rate of filler decomposition and/or with the formation of a more stable ash. However, it has been found that the particle size effect is absent, or less evident, in the cone calorimeter test.35 Similarly, particle size reduction has been shown to enhance fire retardancy in magnesium hydroxide-filled PP in this case, samples were characterized by the UL94 test.36 This raises the question as to whether further reductions in particle size to the nanoscale will lead to an additional increase in flammability performance, and perhaps enable filler overall levels to be significantly reduced. This aspect is considered in a later section. 

In this section, we concentrate on the fundamental impact of particle size reduction on magnetization processes in individual particles. Although not directly related to coercivity, the classical effect of single domain particle formation is described. At small particle size, reversal by coherent rotation tends to be favoured with respect to nucleation/pinning-depinning finally thermal activation effects and macroscopic quantum tunnelling are discussed. 

Equation (5) reduces to the Smith-Ewart equation [Eq. (2)] if c is sef equal to zero and if both sides of Eq. (5) are integrated between <7 = 0 and cr = oo. This reduction further requires the assumption that all rate coefficients forming the elements of Q are independent of population balance Eq. (5) are considerably more general in scope than the Smith-Ewart equation because the inclusion of the size parameter enables the formalism to model the particle formation process, as well as both the kinetics and the evolution of the PSD. 

Furthermore, pharmacokinetic administration, distribution, metabolism and excretion (ADME) factors affect drug bioavailability, efficacy and safety, and, thus, are a vital consideration in the selection process of oral drug candidates in development pipelines. Since solubility, permeability, and the fraction of dose absorbed are fundamental BCS parameters that affect ADME, these BCS parameters should prove useful in drug discovery and development. In particular, the classification can used to make the development process more efficient.For example, in the case of a drug placed in BCS Class II where dissolution is the rate-limiting step to absorption, formulation principles such as polymorph selection, salt selection, complex formation, and particle size reduction (i.e., nanoparticles) could be applied earlier in development to improve bioavailability. 

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