Pharmaceutical disperse system

Content uniformity and long-term stability of a pharmaceutical product are required for a consistent and accurate dosing. Aggregation of dispersed particles and resulting instabilities such as flocculation, sedimentation (in suspensions), or creaming and coalescence (in emulsions) often represent major problems in formulating pharmaceutical disperse systems. 

Rheology is the study of flow and deformation of materials under the influence of external forces. It involves the viscosity characteristics of powders, liquids, and semisolids. Rheological studies are also important in the industrial manufacture and applications of plastic materials, lubricating materials, coatings, inks, adhesives, and food products. Flow properties of pharmaceutical disperse systems can be of particular importance, especially for topical products. Such systems often exhibit rather complex rheological properties, and pharmaceutical scientists have conducted fundamental investigations in this area [58-64],... 

Scott, R.R. A practical guide to equipment selection and operating techniques. In Pharmaceutical Disperse Systems, Lieberman, H.A., Rieger, M.M., Banker, G.S., Eds. Marcel Dekker, Inc. New York, 1989 2, 1-71. 

Various. synthetic and natural hydrophilic polymers are extensively used to enhance the physical stability of pharmaceutical disperse. systems. Examples of these include alginates, carrageenan and xanthan gum, whereas a wide range of synthetic polymers has also been used for this purpose, e.g., cellulose ethers, polyfacrylic acid), PVP and PVA. 

Many polymers are used for the preparation of disperse systems (suspensions and emulsions) in pharmaceutical formulations. Several polymers, both homo- and block-copolymers are used for stabilization of pharmaceutical disperse systems. Their adsorption and conformation on a solid surface are schematically shown in Fig. 2.5. 

B. Idson, in H. A. Lieberman and co-eds.. Pharmaceutical Dosage Forms, Disperse Systems, Vol. 1, Marcel Dekker, New York, 1988, Chapt. 6. 

A disperse system is defined as a heterogenous, two-phase system in which the internal (dispersed, discontinuous) phase is distributed or dispersed within the continuous (external) phase or vehicle. Various pharmaceutical systems are included in this definition, the internal and external phases being gases, liquids, or solids. Disperse systems are also important in other fields of application, e.g., processing and manufacturing of household and industrial products such as cosmetics, foods, and paints. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

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. 

The number of the constituent phases of a disperse system can be higher than two. Many commercial multiphase pharmaceutical products cannot be categorized easily and should be classified as complex disperse systems. Examples include various types of multiple emulsions and suspensions in which solid particles are dispersed within an emulsion base. These complexities influence the physicochemical properties of the system, which, in turn, determine the overall characteristics of the dosage forms with which the formulators are concerned. 

Surfactants are useful in formulating a wide variety of disperse systems. They are required not only during manufacture but also for maintaining an acceptable physical stability of these thermodynamically unstable systems. Besides the stabilizing efficiency, the criteria influencing the selection of surfactants for pharmaceutical or cosmetic products include safety, odor, color, and purity. 

The determination of the zeta potential of particles in a disperse system provides useful information concerning the sign and magnitude of the charge and its effect on the stability of the system (see Sec. II.B) [56, 206 208], It can be of value in the development of pharmaceutical suspensions, particularly if the... 

SE Tabibi, CT Rhodes. Disperse systems. In GS Banker, CT Rhodes, eds. Modem Pharmaceutics, 3rd 16. ed. New York Marcel Dekker, 1996, pp 299-331. 

JG Nairn. Disperse systems. In J Swarbrick, JC Boy-lan, eds. Encyclopedia of Pharmaceutical Technology,... 

RA Nash. Pharmaceutical suspensions. In HA Lieberman, MM Rieger, GS Banker, eds. Pharmaceutical Dosage Forms Disperse Systems, Vol. 1. New York Marcel Dekker, 1988, pp 151-198. 

Reprinted in part, with revisions and updates, by courtesy of Marcel Dekker, Inc., from L. H. Block, Scale-up of disperse systems Theoretical and practical aspects, in Pharmaceutical Dosage Forms Disperse Systems (H. A. Lieberman, M. M. Rieger, and G. S. Banker, eds.), Vol. 3, 2nd ed.. New York Marcel Dekker, 1998 366-378. 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen (55), referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and... 

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