Drug release delivery systems

Controlled drug release delivery systems based on nano- or microparticles/microcapsules. 

Beck, L. R., and Pope, V. Z., Controlled-release delivery systems for hormones. Drugs, 270, 528, 1984. 

In this chapter we present the theory involved in developing sustained- and controlled-release delivery systems and applications of these systems as therapeutic devices. Although suspensions, emulsions, and compressed tablets may demonstrate sustaining effects within the body compared with solution forms of the drug, they are not considered to be sustaining and are not discussed in this chapter. These systems classically release drug for a relatively short period, and their release rates are strongly influenced by environmental conditions. 

FACTORS INFLUENCING ORAL MODIFIED-RELEASE DELIVERY SYSTEM DESIGN AND PERFORMANCE FOR WATER-INSOLUBLE DRUGS... 

L-ORO drug delivery technology, a proprietary controlled-release delivery system invented by ALZA Corporation (Mountain View, California), combines drug solubilization technology enabling... 

A general understanding of the definitions of linear and nonlinear will be helpful when discussing drug input into the body, whether that dose or input is delivered by classic delivery means or by novel controlled release delivery systems. Linear and nonlinear pharmacokinetics are differentiated by the relationship between the dose and the resulting drug concentration. A linear pharmacokinetics system exhibits a proportional relationship between dose and Cp for all doses, whereas nonlinear pharmacokinetics systems do not. 

The regulation of drug input into the body is the core tenet of controlled release drug delivery systems. With advances in engineering and material sciences, controlled release delivery systems are able to mimic multiple kinetic types of input, ranging from instantaneous to complex kinetic order. In this section three of the most common input functions found in controlled release drug delivery systems will be discussed— instantaneous, zero order, and first order. 

Factors analogous to those affecting gut absorption also can affect drug distribution and excretion. Any transporters or metabolizing enzymes can be taxed to capacity—which clearly would make the kinetic process nonlinear (see Linear versus Nonlinear Pharmacokinetics ). In order to have linear pharmacokinetics, all components (distribution, metabolism, filtration, active secretion, and active reabsorption) must be reasonably approximated by first-order kinetics for the valid design of controlled release delivery systems. 

There are multiple volume terms associated with this model V and V2 (volumes of compartments 1 and 2), Vd ss (volume at steady state), Fd,area or V. p, and V extrap- Each is useful, but under specific conditions. These volume terms do not represent a specific physiological space their utility is primarily the conversion of amount of drug into a concentration. Of these many volume terms, Vd ss is probably the most relevant in the design of controlled release delivery systems. 

This volume term also depends on p and/or k10 and overestimates the volume. However, when terminal concentration-time data are used (i.e., distribution is at steady state and elimination is the process significantly altering Cp), this volume term will produce an accurate conversion factor between Cp and the amount of drug in the body. While Vda .a overestimates the volume, it can be useful in the design of controlled release delivery systems, particularly in pulsatile delivery. 

Generally, since the goal of some controlled release delivery systems is to achieve and maintain the drug at a steady-state concentration... 

Achievement of a sufficient input flux of drug. The achievement of sufficient input drug flux is probably the greatest challenge to designing a successful controlled release delivery system. While some controlled... 

Achievement of a desired drug concentration-time profile. Although physiological processes govern the disposition of drug in the body, several pharmacokinetic parameters are still useful for evaluating drugs as candidates for controlled release delivery systems. In addition to potency, the pharmacokinetic parameters systemic clearance Cl, volume of... 

Ideal drug candidate for controlled release delivery systems. From a pharmacokinetic and pharmacodynamic perspective, the ideal drug candidate for controlled release delivery systems would have high potency and... 

Hite, M., Federici, C., Turner, S., and Fassihi, R. Novel design of a self-correcting monolithic controlled-release delivery system for tramadol. Drug Del. Tech. 3 48-55, 2003. 

Osmotic pressure, a colligative property, depends on the concentration of solute (neutral molecule or ionic species) that contributes to the osmotic pressure. Solutions of different concentrations having the same solute and solvent system exhibit an osmotic pressure proportional to their concentrations. Thus a constant osmotic pressure, and thereby a constant influx of water, can be achieved by an osmotic delivery system that results in a constant release rate of drug. Therefore, zero-order release, which is important for a controlled release delivery system when indicated, is possible to achieve using these platforms. In 1974,... 

The principal application of these small osmotic pumps has been as implantable controlled release delivery systems in experimental studies on the effect of continuous administration of drugs. The devices are made with volumes of 0.2-2 mL. Figure 12.18 shows one such device being implanted in a laboratory rat. The delivery pattern obtained with the device is constant and independent of the site of implantation, as shown by the data in Figure 12.19. 

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