Drug particles

Johnson, K., Swindell, A. Guidance in the setting of drug particle size specifications to minimize variability in absorption. Pharm. Res. 1996, 13, 1795-1798. 

S = effective surface area of the drug particles h = thickness of a stationary layer of solvent around the drug particle... 

In addition to these in vitro demonstrations of the importance of the effective surface area of drug particles on dissolution rate, many in vivo studies are available. Phenacetin plasma levels versus time are plotted for three different particle sizes of phenacetin in Fig. 14. Healthy adult volunteers received 1.5-g doses of phenacetin as an aqueous suspension on an empty stomach. The results show that both the rate and... 

In summary, it is the effective surface area of a drug particle that determines its dissolution rate. The effective surface area may be increased by physically reducing the particle size, by adding hydrophilic diluents to the final dosage form, or by adding surface-active agents to the dissolution medium or to the dosage form. 

Various manufacturing processes can affect dissolution by altering the effective surface area of drug particles. Each of the individual processes mentioned here is discussed in more detail in Chapter 9. The effect of adding hydrophilic granulating agents to a dosage form has been discussed earlier (see Sec. III.A). 

Q = saturation solubility of drug (macroparticles) y = interfacial tension between drug particles and the solubilizing fluids M = Molecular weight of the drug r = radius of the microscopic drug particle R = ideal gas constant... 

Disperse systems can be classified in various ways. Classification based on the physical state of the two constituent phases is presented in Table 1. The dispersed phase and the dispersion medium can be either solids, liquids, or gases. Pharmaceutically most important are suspensions, emulsions, and aerosols. (Suspensions and emulsions are described in detail in Secs. IV and V pharmaceutical aerosols are treated in Chapter 14.) A suspension is a solid/liquid dispersion, e.g., a solid drug that is dispersed within a liquid that is a poor solvent for the drug. An emulsion is a li-quid/liquid dispersion in which the two phases are either completely immiscible or saturated with each other. In the case of aerosols, either a liquid (e.g., drug solution) or a solid (e.g., fine drug particles) is dispersed within a gaseous phase. There is no disperse system in which both phases are gases. 

An ophthalmic suspension should use the drug in a microfine form usually 95% or more of the particles have a diameter of 10 pm or less. This is to ensure that the particles do not cause irritation of the sensitive ocular tissues and that a uniform dosage is delivered to the eye. Since a suspension is made up of solid particles, it is at least theoretically possible that they may provide a reservoir in the cul-de-sac for slightly prolonged activity. However, it appears that this is not so, since the drug particles are extremely small, and with the rapid tear turnover rate they are washed out of the eye relatively quickly. 

R Evans. Determination of drug particle size and morphology using optical microscopy. Pharm Technol... 

D = diffusion coefficient of drug S = effective surface area of drug particles h = stationary layer thickness Cs = concentration of solution at saturation C = concentration of solute at time t... 

This chapter provides analytical solutions to mass transfer problems in situations commonly encountered in the pharmaceutical sciences. It deals with diffusion, convection, and generalized mass balance equations that are presented in typical coordinate systems to permit a wide range of problems to be formulated and solved. Typical pharmaceutical problems such as membrane diffusion, drug particle dissolution, and intrinsic dissolution evaluation by rotating disks are used as examples to illustrate the uses of mass transfer equations. 

Mass Transfer from Finely Divided Drug Particles... 

The Higuchi-Hiestand model [43] permits the a priori estimation of the mass transport coefficient for the dissolution of finely divided drug particles. The model relates the particle radius, a(t), with time according to... 

Several mathematical models are available for predicting the dissolution of particles of mixed size. Some are more complex than others and require lengthy calculations. The size of polydisperse drug particles can be represented with a distribution function. During the milling of solids, the distribution of particle sizes most often results in a log-normal distribution. A log-normal distribution is positively skewed such that there can exist a significant tail on the distribution, hence a number of large particles. The basic equation commonly used to describe the particle distribution is the log-normal function,... 

E. K. Anderberg, M. Bisrat, C. Nystrom. Physicochemical aspects of drug release. VII. The effect of surfactant concentration and drug particle size on solubility and dissolution rate of felodipine, a sparingly soluble drug. Int. I. Pharm. 1988, 47, 67-77. 

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