Pharmaceutical Emulsions

1. Pharmaceutical Emulsions PHT 3101 Sept 2012 By: Imanirampa Lawrence(MPS)

2. “Emulsions” :preparations intended for internal use( i.e via oral route Emulsion :others for external, always given different titles whc reflects their use(applications, lotions, creams etc..) Emulsion - a liquid preparation, contains two immiscible liquids(oil and water), one is finely sub divided and uniformly distributed as droplets in the diversion media ,rendered homogenous/stabilized by addition of an emulgent(emulsifying agent) INTRODUCTION

3. Emulgent : ensures the oil phase is finely dispersed throughout the water as minute globules Type of emulsion: 1. oil-in water (O/W)type All oral dose emulsions= o/w type, w/o emulsions- intended for external use why? Oily phase-less present to take, Are difficulty to flavor

4. BP: oral Emulsion an oral liquid, contain one or more active ingredients o/w dispersions, either or both phases may contain dissolved solids(suspended in oral emulsion) Packaged in wide-mouthed bottles 2. w/o emulsion –for external use 3. w/o/w emulsions 4. o/w/o emulsions

5. Emulsification: Enables pharmacist prepare relatively stable, homogenous mixtures of two immiscible liquids(oil and water soluble drugs) Permits administration of a liquid drug in the form of minute globules rather than bulky o/w permits palatable administration of an otherwise distasteful oil, dispersing in a sweetened ,flavored aqueous vehicle Reduction of size of oil globules may render the oil more digestible and more readily absorbed, more effective in its task(increased Purpose of emulsions and emulsification

6. Oral,rectal and topical emulsions (o/w or w/o) administration of oils oil soluble drugs Medicinal agent-irritant to the skin, less irritating Naturally, miscibility or solubility in oil and in water of a medicinal agent dictates to a greater extent the vehicle IM of some water-soluble vaccines provide a slow release(greater response and long lasting immunity) Total parenteral nutrition-sterile o/w emulsion-delivering oily nutrients IVsly

7. On unbroken skin-w/o emulsion applied more evenly,-skin is covered with thin film of sebum w/o is more softening to the skin, Preparation -removed easily from the skin, o/w emulsion is preferred Diminished particle size of internal phase (percutaneous absorption) may be enhanced IM

8. Advantages of emulsions as dosage forms Unpalatable drug -administered in palatable liquid form(code liver oil emulsion) Unpalatable oil-soluble drugs-administered in a palatable form Aqueous phase - easily flavored Oily sensation - easily removed Increased rate of absorption Possible to include two incompatible ingredients in each phase of the emulsion

9. Disadvantages of emulsions as dosage forms Preparation needs shaking well before use Measuring device needed in administration Need degree of technical accuracy to measure a dose Storage conditions may affect stability Bulky, difficult to transport and prone to container breakages Reliable to microbial contamination whc can lead to crack

10. Physical properties ofsuspension and emulsions:-Flocculation and deflocculated sytems-Rheology-Viscosity modifiers

11. Physical properties of suspensions and emulsions Pdt - sufficiently homogenous on shaking the container and removing required amount storage no sedimentation or creaming if so happen resuspended Pdt - thickened in order to reduce the rate of creaming of oily globules Resulting viscosity in right proportions- ease of removal or transfer from container

12. Physical properties of suspensions and emulsions Suspended particles should be small and uniformly sized in order to -smooth, -elegant pdt, -non gritty

13. Flocculation and defloculated sytem Read chapt6,pg90-97 and chapt27, pg 386,pharmaceutics by M.E.Aulton and make some brief notes with few diagrams to illustrate the two terms.

14. Rheology REO means flow LOGY means science of flow An ideal p,ceutical suspension exhibit a high apparent viscosity at low rates of shear so that on storage,suspended particles would either settle slowly /preferably, remain permanently suspended At higher rates of shear, such as those caused by moderate shaking of pdt, the apparent viscosity shd fall sufficiently for the pdt to be poured easily from the container

15. Rheology Pdt for external use shd spread easily without excess drugging, but shd not be so fluidy that it runs off the surface If intended for inj the pdt shd pass easily thru the hypodermic needle with only moderate pressure applied to the plunger Its important for the initial high apparent viscosity to be reformed after a short time to maintain adequate physical stability(further reading ref chapt 4 ,Aulton)

16. Rheology Describe following terms: Plastic (Bingham) flow Pseodoplastic flow Dilatant flow Thixotropy Dilatancy Identify and describe several methods by which rheological properties of an emulsion can be controlled.

17. Viscosity modifiers Materials -most widely used for the modification of suspension viscosity Polysaccharides(acacia,tragacanth,alginate starch,xanthan gum) Water soluble cellulose(methyl cellulose,hydroxyethylcellulose,SCMC, microcrystalline) Hydrated silicates(bentonite,mg aluminium silicate,hectorite) Carbomers(colloidal silicon dioxide)

18. Polysaccharides Acacia Is a natural material,suspending agent for extemporaneously prepared suspensions Not a good thickening agent largely used due to its action as a protective colloid. Useful in tinctures of resinous materials formulations – whc ppte on addition to water coats precipitated resin, forming protective colloid before any electrolyte(which should be well diluted) is added. Not very effective for dense powders, remedy combin with other thickener(tragacanth,starch and sucrose)

19. Polysaccharides Tragacanth: Form viscous aqueous solutions Its thixotropic and pseudoplastic properties make it a better thickening agent than acacia used both for internal and external products Like acacia it is used for the extemporaneous preparation of suspensions with a short shelf-life Stable over a pH range of 4-7.5

20. Polysaccharides Takes several days to hydrate fully after dispersion in water is the period for maximum viscosity of its dispersions and is heating labile Has several grades and best quality of these is a suitable pharmaceutical suspending agent.

21. Polysaccharides Alginates Alginic acid, a polymer of D-mannuronic acid Prepared from kelp, and its salts have suspending properties similar to those of tragacanth Alginate mucilages must not be heated above 60°C -depolymerization - loss in viscosity Are most viscous immediately ,but fall to a fairly constant value after about 24 hours.

22. Alginates maximum viscosity over a pH range of 5-9, and pptes at low pH Sodium alginate (Manucol) -most widely used material in this class is anionic therefore incompatible with cationic materials and heavy metals calcium chloride + sodium alginate dispersion = calcium alginate,with much higher viscosity OTHERS: Starch Xanthan gum

23. Water-soluble celluloses Several cellulose derivatives are available that will disperse in water to produce viscous colloidal solutions suitable for use as suspending agents examples: Methylcellulose Hydroxyethylcellulose Carmellose sodium (sodium carboxymethylcellulose Microcrystalline cellulose

24. Water-soluble celluloses Methylcellulose Is a semi-synthetic polysaccharide produced by the methylation of cellulose Several grades exist-depending on their degree of methylation and chain length longer the chain, more viscous is its solution i.e. , a 2% solution of methylcellulose 20 exhibits an apparent viscosity of 20 millipascal seconds (mPa s) and methylcellulose 4500 has value of 4500 mPa s at 2% concentration

25. Hydrated silicates Classified into: 1. Bentonite, 2. Magnesium aluminium silicate (aka veegum,orattapulgite) and 3. Hectorite, and Belong to a group called montmorillonite clays Hydrate readily, absorbing up to 12 times their weight of water, particularly at elevated temperatures. Form gels that are thixotropic and therefore have useful suspending properties As with most naturally occurring materials they may be contaminated with spores, and this must be borne in mind when considering a sterilization process and choosing a preservative system

26. Carbomers Aka carboxypolymethylenes Are totally synthetic copolymer of acrylic acid and allyl sucrose its concentrations of up to 0.5%- used mainly for external application, and some grades can be taken internally forms acidic, low-viscosity solutions when dispersed in water and at pH between 6 and 11, become highly viscous

27. Colloidal silicon dioxide Aka Aerosil When dispersed in water this finely divided Product will aggregate, forming a three-dimensional network concns up to 4% for external use, used for thickening non-aqueous suspensions

28. Types of Emulsion • An oil-in-water (o/w) emulsion is a system where the oil (internal phase) is dispersed throughout the aqueous (external) phase. • A water-in-oil (w/o) emulsion is a system where the water is dispersed throughout the oil. • Multiple emulsions may also be achieved (w/o/w or o/w/o) • May be of interest when formulating delayed release products. • Emulsions and creams are similar to suspensions because they are fundamentally unstable systems

29. Tests for identification of emulsion type Several simple methods are available for distinguishing between o/w and w/o emulsions The most common of these involve: Miscibility tests with oil or water: emulsion- miscible with liquids that are miscible with its continuous phase; Conductivity measurements: aqueous continuous phases-readily conduct electricity, oily continuous phases wont; staining tests. Water-soluble and oil-soluble dyes are used, one of which will dissolve in, and colour the continuous phase

30. How to Distinguish Between Types of Emulsion

31. Characteristics of an acceptable Pharmaceutical Emulsion • Physical stability • No phase separation • Flow properties of the emulsion/cream should allow the formulation to be easily removed from its container • If the formulation is a topical preparation, it must be easily spread on the skin • The formulation must be aesthetically and texturally pleasing • If the emulsion is for oral use, it must have a suitable flavour • If the formulation is for topical application, it must have the correct feel (texture)

32. CHOICE OF EMULSION TYPE Decision as to whether an o/w or a w/o emulsion is to be formulated will eliminate many unsuitable emulsifying systems Fats or oils for oral administration, either as medicaments in their own right or as vehicles for oil-soluble drugs, are invariably formulated as oil-in- water emulsions In this form they are pleasant to take, and the inclusion of a suitable flavour in the aqueous phase will mask any unpleasant taste

33. CHOICE OF EMULSION TYPE Emulsions for intravenous administration must be of the o/w type, Emulsions for intramuscular injections can also be formulated as w/o products if a water-soluble drug is required for depot therapy. Emulsions are most widely used for external application Semisolid emulsions are termed creams(o/w and w/o types)and more fluid preparations are called either lotions or, if intended for massage into the skin, liniments

34. Choice of emulsion type o/w emulsions is used for the topical application of water-soluble drugs,mainly for local effect o/w emulsions do not have the greasy texture associated with oily bases and therefore pleasant to use and o/w emulsions washed from skin surfaces. w/o emulsions have an occlusive effect by hydration of the upper layers of the stratum corneum and the inhibition of evaporation of eccrine secretions This may influence the absorption rates of drugs from these preparations

35. Choice of emulsion type w/o emulsion is also useful for cleansing the skin of oil-soluble dirt, and its greasy texture is not always cosmetically acceptable Oil-in-water emulsions not good cleansers but are usually more acceptable to the consumer, particularly for use on the hands Moisturising creams, designed to prevent moisture loss from the skin and inhibit drying of the stratum corneum,are more efficient if formulated as w/o emulsions,which produce a coherent, water-repellent film

36. Choice of oil phase In many instances the oil phase of an emulsion is the active agent, and therefore its concentration in the product is predetermined Liquid paraffin, castor oil,cod liver oil and arachis oil are all examples of medicaments which are formulated as emulsions for oral administration Cottonseed oil, soya bean oil and safflower oil are used for their high calorific value in emulsions for intravenous feeding, And turpentine oil and benzylbenzoate examples of externally applied oils that are formulated as emulsions

37. Choice of oil phase Many emulsions for external use contain oils that are present as carriers for the active agent Type of oil used may also have an effect both on the viscosity of the product and on the transport of the drug into the skin One of the most widely used oils for this type of preparation is liquid paraffin Liquid paraffin is one of a series of hydrocarbons, which also includes hard paraffin, soft paraffin and light liquid paraffin They can be used individually or in combination with each other to control emulsion consistency This will ensure that the product can be spread easily but will be sufficiently viscous to form a coherent film over the skin.

38. Choice of oil phase The film-forming capabilities of the emulsion can be further modified by the inclusion of various waxes, such as beeswax, carnauba wax or higher fatty alcohols Continuous films can therefore be formed that are sufficiently tough and flexible to prevent contact between the skin and aqueous-based irritants These preparations are called barrier creams, and many are of the w/o variety inclusion of silicone oils, such as dimethicone at 10-20%, which have exceptional water-repellent properties, may also permit the formulation of o/w products that are equally effective.

39. Choice of oil phase A variety of fixed oils of vegetable origin are also available, the most widely used being arachis, sesame, cottonseed and maize Those expressed from seeds or fruits are often protein rich and contain useful vitamins and minerals They are often, therefore, formulated for oral use as emulsions Because of their lack of toxicity they can be used both internally and externally as vehicles for other materials

40. Choice of emulsifying agent Toxicity and irritancy considerations The choice of emulgent to be used does not depend only on its emulsifying ability, but also on its route of administration and, consequently, on its toxicity Although there is no approved list of emulsifying agents for use in pharmaceutical products there is an approved list of emulsifiers as food additives for use in the European Union It's assumed that emulsifiers contained in this list would be suitable for internally used pharmaceutical emulsions

41. Choice of emulsifying agent(EA) It can be assumed that emulsifiers contained in this list would be suitable for internally used pharmaceutical emulsions The regulations mainly include naturally occurring materials and their semisynthetic derivatives, such as the polysaccharides, as well as glycerol esters, cellulose ethers, sorbitan esters and polysorbates

42. Choice of emulsifying agent(EA) It will be noted that most of these are non-ionic, having a tendency to be less irritant and less toxic than their anionic, and particularly their cationic counterparts The concentrations of ionic emulsifying agents necessary for emulsification will be irritant to the gastrointestinal tract and have a laxative effect, and should not be used for oral emulsions Cationic surfactants generally are toxic even at lower concentrations The emulgent cetrimide is limited to externally used preparations, where its antiseptic properties are of use.

43. Choice of emulsifying agent(EA) Some emulgents, such as the anionic alkali soaps, often have a high pH and are thus unsuitable for application to broken skin Even on normal intact skin with a pH of 5.5, the application of such alkaline materials can cause irritation Some emulsifiers,in particular, wool fat can cause sensitization reactions in susceptible people

44. Choice of emulsifying agent(EA) When choosing an emulgent for parenteral use it must be realized that only certain types of non-ionic material are suitable i.e: lecithin, polysorbate 80, methylcellulose, gelatin and Serum albumin.