Stability of Pharmaceutical Suspension-1 PDF

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IdolizedFrancium8721

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University of Gezira

Deina Elraiah Mohamed El Hassan

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pharmaceutical technology suspension stability zeta potential pharmaceutics

Summary

This document discusses the stability of pharmaceutical suspensions. It covers topics such as sedimentation, particle-particle interactions, caking, and the relationship between zeta potential and stability. The document also details the electrical properties of dispersed particles and the role of adsorption of ions on the surface, which are crucial in achieving stable suspensions.

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‫رلبلنللا م هللا مسب‬ Stability of Pharmaceutical SUSPENSION-1 Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University) Pharmaceutical suspensi...

‫رلبلنللا م هللا مسب‬ Stability of Pharmaceutical SUSPENSION-1 Deina Elraiah Mohamed El Hassan Master degree of Pharmaceutical Technology (University of Gezira) PhD holder of Pharmaceutical Technology (Karary University) Pharmaceutical suspensions are fundamentally unstable, leading to: I. Sedimentation, II. Particle–particle interactions and, III. Caking (compaction). Zeta potential and its relationship to stability Most suspension particles dispersed in water have a charge acquired by Ø Specific adsorption of ions or Ø Ionisation of ionisable surface groups, if present. If the charge arises from ionisation, the charge on the particle will depend on the pH of the environment. The magnitude of the charge can be determined by measurement of the electrophoretic mobility of the particles in an applied electrical field. Zeta potential can be used as a reliable guide to the magnitude of electric repulsive forces between particles. Changes in zetal potential on the addition of flocculating agents, surfactants and other additives can then be used to predict the stability of the system. The use of thickeners such as sodium carboxy methyl cellulose or bentonite hinders the movement of the particles by production of a viscous medium, so that sedimentation is delayed. To gain an understanding of the physical stability of suspensions it is necessary to consider briefly two phenomena: (1) The electrical properties of dispersed particles. (2) The effect of distance of separation between particles on their subsequent interaction. Electrical properties of dispersed particles § Dispersion within an aqueous medium, particles may acquire a charge due to either the ionisation of functional groups on the drug molecule and/or adsorption of ions to the surface of the particle. § Ionisation of functional groups insoluble drug particles may possess groups at the surface that will ionise as a function of pH, e.g. COOH, NH2. § In this situation the degree of ionisation is dependent on the pKa of the molecule and the pH of the surrounding solution. Adsorption of ions on to the surface of the particle § Immersion in an aqueous solution containing electrolytes, ions may be adsorbed on to the surface of the particle. § Furthermore, in the absence of added electrolytes, preferential adsorption of hydroxyl ions on to the surface of the particle will occur. § Hydronium ions, are more hydrated than hydroxyl ions and are therefore more likely to remain within the bulk medium. § Adsorption of ions on to the surface, a phenomenon referred to as the electrical double layer (Figure1) Ions, e.g. cations, are adsorbed on to the surface of the particle, leaving the anions and remaining cations in solution. Ø Anions are then electrostatically attracted to the (positive) surface of the particle. Ø The presence of these anions will repel the subsequent approach of further anions. Ø This is referred to as the first section of the double layer and is therefore composed of adsorbed ions on the surface, counter ions and bound hydrated solvent molecules. Ø The boundary between the first and second layers of the electrical double layer is referred to as the Stern plane. Ø The second layer contains predominantly hydrated counter ions that are loosely attracted to the surface of the particle, the features of which include: a) This second layer will possess a potential, referred to as the zeta potential. b) If the particle is rotated, this second layer forms the shear plane, i.e. the effective surface. The relationship between distance of separation and the interaction between particles § The interaction between suspended particles in a liquid medium is related to the distance of separation between the particles. § In principle, three states of interaction are possible: 1. No interaction, in which the particles are maintained sufficiently distant from one another. In the absence of sedimentation this is the thermodynamically stable state. 2. Coagulation (agglomeration), in which the particles form an intimate contact with each other. This results in the production of a pharmaceutically unacceptable formulation due to the inability to redisperse the particles upon shaking. 3. Loose aggregation (floccules), in which there is a loose reversible interaction between the particles, enabling the particles to be redispersed upon shaking. § The interaction (attraction/repulsion) between particles that have been dispersed in a liquid medium has been quantitatively described by Derjaguin, Landau, Verwey and Overbeek. § In the simplest form the ‘DLVO’ theory assumed that, when dispersed in a liquid medium, particles will experience (interaction between the electrical double layers of each particle) Repulsive forces and attractive (London/van der Waals) forces. § The overall energy of interaction between the particles (V t ) can therefore be described as an addition of the energies of attraction ( Va ) and repulsion (Vr ), i.e. V t=V a + V r. Relationship between the overall energy of interaction between two particles and their distance of separation In this, three main regions may be observed: 1. The primary minimum Ø This is a region of high attraction between particles. Ø Particles that interact at distances corresponding to the primary minimum will irreversibly coagulate and the formulation so produced will be physically unstable. 2. The primary maximum Ø This region is responsible for the repulsion between particles, the magnitude of which is controlled by the zeta potential at the shear plane of the particles. Ø This region prevents the particles from interacting at close distances. Ø The magnitude of the primary maximum is affected by the presence and concentration of electrolytes. Ø Increasing the concentration of electrolyte decreases the thickness of the double layer, thereby reducing the zeta potential. 3.The secondary minimum Ø The secondary minimum is a region where attractive forces predominate; however, the magnitude of the attraction is less than that at the primary minimum. Ø Particles located at the secondary minimum are termed floccules, this process being termed controlled flocculation. Ø Furthermore, the interaction between the particles may be broken by shaking, thereby enabling the removal of an accurate dose. Diagrammatic representation of the over all interactive energy between two particles and their distance of separation. separation

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