Coarse Dispersions. Ms. K.D.S.V. Karunanayaka B.Pharm (Peradeniya) Department of Pharmacy Faculty of Health Sciences, OUSL

Transcription

1 Coarse Dispersions Ms. K.D.S.V. Karunanayaka B.Pharm (Peradeniya) Department of Pharmacy Faculty of Health Sciences, OUSL

2 Introduction Liquid Dosage Forms Monophasic Biphasic Solutions Suspensions Emulsions

3 Introduction

4 Coarse Dispersion-Suspension Properties of Suspensions Theories Involved in Disperse Phase Types of Suspensions Method of Floccules Formation Stability of Suspensions

5 Properties of Suspensions Good pourability Good organoleptic properties Uniform particle size distribution Ease of re-dispersion Physically and chemically stable Resistant against microbial contamination

6 Theories Involved in Disperse Phase Interfacial phenomenon Electrical Double layer and Zeta potential Sedimentation Concept DLVO (Derjaguin Landau Verwey and overbeek) theory

7 Types of Suspensions 1. According to the route of administration Oral Topical Parenteral Ophthalmic 2. According to nature of dispersed phase and methods of preparation The suspensions are classified as suspensions containing diffusible solids, in diffusible solids, poorly wettable solids, precipitate forming liquids and products of chemical reactions. 3. According to nature of sediment Flocculated Suspensions, Non-flocculated (Deflocculated) Suspensions

8 Types of Suspensions

9 Various approaches for developing suspensions

10 Method of Floccules Formation Electrolytes Electrolytes decrease electrical barrier between the particles and bring them together to form floccules. They reduce zeta potential near to zero value that results in formation of bridge between adjacent particles, which lines them together in a loosely arranged structure. Electrolytes act as flocculating agents by reducing the electric barrier between the particles, as evidenced by a decrease in zeta potential and the formation of a bridge between adjacent particles to link them together in a loosely arranged structure.

11 Method of Floccules Formation

12 Method of Floccules Formation Surfactants Both ionic and non-ionic surfactants can be used to bring about flocculation of suspended particles. Optimum concentrations of surfactants bring down the surface free energy by reducing the surface tension between liquid medium and solid particles. This tends to form closely packed agglomerates. The particles possessing less surface free energy are attracted towards to each other by van der waals forces and forms loose agglomerates.

13 Method of Floccules Formation Polymers Polymers possess long chain in their structures. The part of the long chain is adsorbed on the surface of the particles and remaining part projecting out into the dispersed medium. Bridging between these later portions, also leads to the formation of flocs. Liquids Here like granulation of powders, when adequate liquids are present to form the link, compact agglomerate is formed. The interfacial tension in the region of the link, provide the force acting to hold the particles together. Hydrophobic solids may be flocculated by adding hydrophobic liquids.

14 Stability of Suspensions In case of dispersion of positively charged particles that is flocculated by addition of an aninonic electrolyte like monobasic potassium phosphate. The physical stability of the system is enhanced by addition of carboxymethylcellulose, Carbopol 934, veegum, tragacanth or bentonite either alone or in combination. No physical incompatibility is recorded as majority of hydrophilic colloids are negatively charged and are compatible with anionic flocculating agents. When a flocculated suspension of negatively charged particles with a cationic electrolyte is prepared (aluminum chloride), the addition of hydrocolloid may result in an incompatible product resulting in stingy mass, which has no suspending action, and settle rapidly. In such a condition protective agent is added to change the sign on the particles from the negative to positive is employed which can also be achieved by the adsorption onto the particle surface by fatty acid amine or gelatin. Thus, an anionic electrolyte is used to produce floccules that are compatible with negatively charged suspending agent.

15 Quality Control Tests for Suspensions Sedimentation volume Redispersibility is the major consideration in assessing the acceptability of a suspension. The measurement of the sedimentation volume and its ease of redispersion form two of the most common basic evaluative procedures. The sedimentation volume is the simple ratio of the height of sediment to initial height of the initial suspension. The larger the value better is the suspend ability. Particle size and size distribution The freeze-thaw cycling technique used to assess suspension for stress testing and stability testing resulting increase of particle growth and may indicate future state after long storage. It is of importance to study the changes for absolute particle size and particle size distribution. Microscopic method allows the observer to view the actual particles.

16 Quality Control Tests for Suspensions Rheological studies Help in determining the settling behavior of the suspension. Brookefield viscometer with variable shear stress control can be used for evaluating viscosity of suspensions. It consist of T-bar spindle which is lowered into the suspension and the dial reading is noted which is a measure of resistance the spindle meets at various levels in the suspension. Stability testing The valid temperature data could be obtained that will be useful in the estimation of the physical stability of a product at normal storage conditions. The extended aging tests must be employed under various conditions to obtain the desired information.

17 Quality Control Tests for Suspensions Sustained release suspensions A suspension usually gives a longer duration of action as compared to an aqueous solution when given intramuscularly or subcutaneously. The sustained release by suspensions is achieved by decreasing surface area, diffusion coefficient and solubility. Ex:- Insulin, Penicillin G. Insulin is normally administered subcutaneously and it precipitates as an insoluble complex in the presence of zinc chloride and depending on the ph either an amorphous or crystalline form results. The crystalline form is less soluble than the amorphous form and result in longer duration of action. Extended insulin zinc suspension USP consist of crystalline zinc complex.

18 Coarse Dispersion-Emulsion Types of Emulsions Primary and Secondary Emulsion Emulsion Type and Means of Detection Pharmaceutical Applications of Emulsions Theories of Emulsification Selection of Emulsifying Agents Using HLB Method Control of Emulsion Type during Formulation Factors that Affects the Choice of Emulsion Type Stability of Emulsion

19 Types of Emulsions Oil in water emulsions Water in oil emulsions Multiple emulsions Microemulsions

20 Types of Emulsions Oil in water emulsion (o/w) Water in oil emulsion (w/o) Oil is the dispersion medium and water is the dispersed phase Water is the dispersion medium and oil is the dispersed phase They are greasy and not water washable They are non greasy and easily removable from the skin surface They are used externally to provide cooling effect e.g. vanishing cream They are used externally to prevent evaporation of moisture from the surface of skin e.g. Cold cream Water soluble drugs are more quickly released from o/w emulsions Oil soluble drugs are more quickly released from w/o emulsions They are preferred for formulations meant for external use like They are preferred for formulations meant for internal use as creams. bitter taste of oils can be masked. W/O emulsions go not give, a positive conductivity test as oil is O/W emulsions give a positive conductivity test, as water is the the external phase, which is a poor conductor of electricity.

21 Primary and Secondary Emulsion Primary emulsion containing one internal phase, for example, oil-in-water emulsion (o/w) and water-in-oil emulsion (w/o). Secondary emulsion or multiple-emulsion contains two internal phase, for instance, o/w/o or w/o/w. It can be used to delay release or to increase the stability of the active compounds.

22 Primary and Secondary Emulsion

23 Emulsion Type and Means of Detection Dilution Test The Dilution Test is based on the solubility of external phase of emulsion. 1. o/w emulsion can be diluted with water. 2. w/o emulsion can be diluted with oil.

24 Emulsion Type and Means of Detection

25 Emulsion Type and Means of Detection Conductivity Test Water is good conductor of electricity whereas oil is non-conductor. Therefore, continuous phase of water runs electricity more than continuous phase of oil.

26 Emulsion Type and Means of Detection Dye solubility test Water-soluble dye will dissolve in the aqueous phase. Oil-soluble dye will dissolve in the oil phase.

27 Emulsion Type and Means of Detection Fluorescence test Oils give fluorescence under UV light, while water doesn t. Therefore, O/W emulsion shows spotty pattern while W/O emulsion fluoresces. Cobalt Chloride Test When a filter paper soaked in cobalt chloride solution is added to an emulsion and dried, it turns from blue to pink, indicating that the emulsion is o/w type.

28 Pharmaceutical Applications of Emulsions To mask the taste O/W is convenient means of orally administration of water-insoluble liquids O/W emulsion facilitates the absorption of water-insoluble compounds comparing to their oily solution preparations (e.g. vitamins) Oil-soluble drugs can be given parentrally in form of oil-in water emulsion. (e.g Taxol) Emulsion can be used for external application in cosmetic and therapeutic uses.

29 Theories of Emulsification In-case of two immiscible liquids Cohesive force between the molecules of each separate liquid exceeds adhesive force between two liquids. This is manifested as interfacial energy or tension at boundary between the liquids.

30 Theories of Emulsification Therefore, to prevent the coalescence and separation, emulsifying agents have been used. Surface active agent Hydrophilic colloids Finely divided solid particles

31 Monomolecular Adsorption Surface-active agent is molecules, which have two parts, one is hydrophilic and the other is hydrophobic. Upon the addition of Surface-active agent, they tend to form monolayer film at the oil/water interface. The functions of surface-active agents to provide stability to dispersed droplets are as following Reduction of the interfacial tension Form coherent monolayer to prevent the coalescence of two droplet when they approach each other Provide surface charge which cause repulsion between adjust particles Combination of surface-active agents is used most frequently. The combination should form film that closely packed and condensed

32 Multimolecular Adsorption Hydrophilic colloids form multimolecular adsorption at the oil/ water interface. They have low effect on the surface tension. Their main function as emulsion stabilizers is by making coherent multimolecular film. (O/W emulsions)

33 Solid Particle Adsorption Finely divided solid particles are adsorbed at the surface of emulsion droplet to stabilize them. Those particles are wetted by both oil and water (but not dissolved) and the concentrations of these particles form a particulate film that prevents the coalescence. Particles that are wetted preferentially by water from o/w emulsion, whereas those wetted more by oil form w/o emulsion Note that they are very rare to use and can affect rheology of the final product Size of the particle is very important, larger particles can lead to coalescence

34 Natural emulsifying agents Egg yolk: it contains phospholipids and cholesterol. The main withdraw back is that spoils quickly; therefore, it cannot be used in industry. It is used for extemporaneous preparation. Wool fat: anhydrous lanolin, it is used to prepare w/o emulsion for external uses. Starch: it forms starch mucilage and it is restricted for enemas preparation. Cholesterol: it has stabilizing action; therefore, another emulsifier should be included.

35 Selection of Emulsifying Agents Using HLB Method The system is called the HLB (hydrophile-lipophile balance) system and has an arbitrary scale of HLB numbers are experimentally determined for the different emulsifiers. HLB RANGE USE Antifoaming agents W/O emulsifying agent Wetting agents O/W emulsifying agent Detergents Solubilizing agents

36 Control of Emulsion Type during Formulation Volume of internal and external phases controls the type of emulsion: The smaller volume will be for the internal phase and the larger volume will be for external phase. In some cases, internal phases can be more than 50% of the total volume (see the following section) Dominance of polar and non-polar characteristic of emulsifying agents (relative solubility of emulsifying agent in water and oil): Dominance of polar part results in formation of o/w emulsion and dominance of non-polar part results in formation of w/o emulsion. Note that polar groups are better barriers than non-polar. Therefore, o/w emulsion can be prepared with more than 50 % of oil phase internal phase.

37 Factors that Affects the Choice of Emulsion Type The choice of emulsion depends on; Properties and uses of final products The other material required to be present Oil-soluble drug is prepared in o/w emulsion due its solubility and its taste can be masked by adding flavouring agents. For intravenous injection (IV) o/w, emulsion is the only type could be used. For intramuscular injection (IM) both o/w and w/o types of emulsion could be used. Watersoluble drug can be prepared in w/o emulsion to get prolonged action (depot therapy) Topical application: Semisolid emulsions are called creams and lotions.

38 Characteristics of O/W and W/O emulsion for topical application Oil in water emulsion Water in oil emulsion For insoluble drug For water soluble drug For local effect Can be use to hydrate the upper layer of stratum corneum (moisturizing cream) Easily to wash from skin Can increase the absorption of drug from these formulation Doesn t have greasy texture of oily preparation Can be used to clean skin from dirt Acceptable by consumer Not acceptable by consumer

39 Stability of Emulsion An emulsion is considered physically unstable if: a) The internal phase tends to form aggregates of globules. b) Large globules or aggregates of globules rise to the top or fall to the bottom of the emulsion to form a concentrated layer of the internal phase. c) All or part of the liquid of the internal phase becomes "unemulsified on the top or bottom of the emulsion. Separation of the internal phase from the external phase is called cracking of the emulsion. This is irreversible. -Emulsions may be adversely affected by microbial contamination. -Protect emulsions against the extremes of cold and heat.

40 Stability of Emulsion Phase Inversion The relative volume of internal and external phases of an emulsion is important. The increasing of internal concentration may increase viscosity up to a certain point. Viscosity will decrease after that point. At this point the emulsion has undergone inversion.

41 Gels and Magmas Gels are defined as semisolid systems consisting of dispersions made up of either small inorganic particles or large organic molecules enclosing or interpenetrated by a liquid. Magmas or Milks are gels consisted of floccules of small distinct particles. Gels and Magmas are considered colloids because they contain particles within the range of colloidal dispersions. Examples of Magmas & Gels: Bentonite Magma, NF: Preparation of 5% bentonite, a native, colloidal hydrated aluminium silicate, in purified water. Aluminum Hydroxide Gel, USP: This is an aqueous suspension of a gelatinous precipitate composed of insoluble aluminum hydroxide and hydrated aluminum oxide, equivalent to about 4% of aluminum oxide. Milk of Magnesia, USP: This is a preparation containing between 7 and 8.5% of Magnesium hydroxide.

42 Re-capture

43 Re-capture Coarse Dispersion-Suspension Properties of Suspensions Theories Involved in Disperse Phase Types of Suspensions Method of Floccules Formation Stability of Suspensions

44 Re-capture Coarse Dispersion-Emulsion Types of Emulsions Primary and Secondary Emulsion Emulsion Type and Means of Detection Pharmaceutical Applications of Emulsions Theories of Emulsification Selection of Emulsifying Agents Using HLB Method Control of Emulsion Type during Formulation Factors that Affects the Choice of Emulsion Type Stability of Emulsion

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