Ida Kusuma Pharmaceutical Engineering - 5 Exercise 3 1.

. Explain the theory and sedimentation behavior of flocculated and deflocculated suspension and the relevance with pharmaceutical suspension dosage form. Flocculation is the formation of light, fluffy groups of particles held together by weak Van der Waal's forces. Even the smallest particles are involved in flocs, so the supernatant appears clear. The formed flocks are loose aggregates and will cause increase in sedimentation rate due to increase in size of particles. It means that flocculated suspensions sediment more rapidly. Here, the sedimentation depends not only on the size of the flocs but also on the porosity of flocs. In flocculated suspension the loose structure of the rapidly sedimenting flocks tends to preserve in the sediment, which contains an appreciable amount of entrapped liquid. The volume of final sediment is thus relatively large and is easily redispersed by agitation. Deflocculation is the absence of association which occurs when repulsive forces between particles predominate. If repulsion forces prevail, the particles separate or deflocculate. Particles in these systems settle very slowly in stages, but ultimately form dense sediment which is considerably more compact than the corresponding sediment of a flocculated system. Particles at the bottom of the cake are also gradually pressed together by the weight of the ones above. Individual particles are settling, so rate of sedimentation is slow which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation. This phenomenon also called cracking or claying. In deflocculated suspension larger particles settle fast and smaller remain in supernatant liquid so supernatant appears cloudy.

Ida Kusuma Pharmaceutical Engineering - 5 2. Advantages and disadvantages of flocculated and deflocculated system in pharmaceutical preparation. Flocculated system Advantages Ease in re-dispersion Clear supernatant Sediment doesnt form cake Deflocculated system Advantages Slow sedimentation rate Low sedimentation volume Pleasing in appearance Disadvantages Difficult to re-disperse Cloudy supernatant Sediment forms cake Disadvantages Fast sedimentation rate High sedimentation volume Bad appearance because of the flocks

3. Explain the electrolytes and zeta potential related with the stability of suspension system. Zeta potential is a physical property which is exhibited by any particle in suspension. It can be used to optimize the formulations of suspensions and emulsions. All particles in suspension exhibit a zeta potential, or surface charge due to their ionic characteristics and dipolar attributes. The zeta potential is defined as the difference in potential between the surface of the tightly bound layer (shear plane) and electro-neutral region of the solution. Zeta potential influences a wide range of properties of colloidal materials, such as their stability and interaction with electrolytes.

Since most colloids, particularly those stabilised by ionic surfactants, are charged, it is not surprising that they interact with electrolytes in a complex manner. Ions of charge opposite to that of the surface (counterions) are attracted to it, while ions of like charge (co-ions) are repelled from it. Consequently the concentrations of ions near the surface are not the same as those in the bulk of the solution (i.e. at a long distance from the surface). The major area of application of colloid-electrolyte phenomena is to understand stability and flocculation effects. The simplest model of these phenomena arises directly from the DLVO (Deryaguin- Landau-Verwey-Overbeek) theory. This simply states that the stability of

Ida Kusuma Pharmaceutical Engineering - 5 the colloid is a balance between the attractive Van der Waals forces and the electrical repulsion due to the surface charge. If the zeta potential falls below a certain level, the colloid will aggregate due to the attractive forces. Conversely, a high zeta potential maintains a stable system. The point at which electrical and Van der Waals forces exactly balance can be identified with a specific electrolyte concentration, known as the critical flocculation concentration or CFC. Indifferent ions cause the zeta potential to continuously decline at high concentration, so we see a single CFC, and the colloid aggregates at all higher electrolyte concentrations. In contrast, specifically adsorbed ions cause charge reversal that may be sufficient to re-stabilise the colloid. In this case we will see an upper and lower CFC, with a region of instability between them.

4. Multiple emulsions are divided into two, w/o/w and o/w/o. Explain why. Multiple emulsions are the emulsion system in which the dispersed phase contains smaller droplets that have the same composition as the external phase. This is made possible by double emulsification hence the systems are also called as double emulsion. In O/W/O systems an aqueous phase (hydrophilic) separates internal and external oil phase. In other words, O/W/O is a system in which water droplets may be surrounded in oil phase, which in true encloses one or more oil droplets. In W/O/W systems, an organic phase (hydrophobic) separates internal and external aqueous phases. In other words, W/O/W is a system in which oil droplets may be surrounded by an aqueous phase, which in turn encloses one or several water droplets. These systems are the most studied among the multiple emulsions. The immiscible oil phase, which separates two miscible aqueous phases is known as liquid membrane and acts as a different barrier and semi-permeable membrane for the drugs or moieties entrapped in the internal aqueous phase.

Ida Kusuma Pharmaceutical Engineering - 5

Multiple emulsion system possesses adequate biocompatibility, complete biodegradability and versatility in terms of different oils and emulsifiers being used. Both hydrophilic and hydrophobic drugs can be entrapped and protected, drug targeting especially to reticuloendothelial system (RES), taste masking and for slow or controlled delivery of drugs.