BANGABANDHU SHEIKH MUJIBUR RAHMAN SCIENCE AND TECHNOLOGY UNIVERSITY GOPALGANJ-8100 AN ASSIGNMENT ON Course Title : Pharmaceutical Technology - 2 Course code : ACCE-305 Topic : EMULSION Date : 09-07-2021 Submitted By Name: Aqib Adnan Shafin Student ID: 17ACE034 Session: 2017-2018 3rd Year 1st Semester Department: Applied Chemistry & Chemical Engineering, BSMRSTU, Gopalganj-8100. Submitted To Name: Rifat Ara Masud Lecturer Department: Applied Chemistry & Chemical Engineering, BSMRSTU, Gopalganj-8100. 1 INDEX TOPICS PAGE NO. What is Emulsion? 2 Types of Emulsion 2-3 Pharmaceutical Applications of Emulsions 4 Identification Tests for Types of Emulsions 4-7 Bancroft’s Rule 7-9 Reference 9-10 2 EMULSION An Emulsion is a thermodynamically unstable system consisting of two immiscible liquid phases, one of which is dispersed/ distributed as globules/droplets (internal or dispersed phase) in the other liquid medium (external or continuous phase) stabilized by a third substance called an emulsifying agent [1]. Fig : Emulsion[2] The two well known examples of emulsions are[1] : 1) Milk in which the particles of the liquid fat are dispersed in water. 2) Cod liver oil emulsion in which water is dispersed in the oil. By considering particle size, pharmaceutical emulsions can be [3] : Macroemulsions (droplets size usually exceeds 10 mm) Miniemulsions (droplets size usually 0.1–10 µm) Microemulsions (droplets size usually 100-600 nm) Nanoemulsions (droplets size usually below 100 nm) Types of emulsion : Emulsions typically consist of a polar (e.g., aqueous) and a relatively nonpolar (e.g., an oil) liquid phase[3]. The two basic types of emulsions are[3] – 1) Oil-in-water (O/W) emulsion : If the oil droplets are dispersed throughout the water phase, the emulsion is called oil in water (O/W) [2]. 3 Fig : Oil-in-water (O/W) emulsion[2] 2) Water-in-oil (W/O) emulsion : If the water droplets are dispersed throughout the oil phase, the emulsion is called oil in water (W/O)[2]. Fig : Water-in-oil (W/O) emulsion[2] However, depending upon the need, more complex systems referred to as “double emulsions” or “multiple emulsions” can be made[3]. Multiple emulsions are complex systems. They can be viewed as emulsions of emulsions. It is a complex type emulsion system in which the oil-in-water or water-in-oil emulsions are dispersed in another liquid medium[2]. Fig : Multiple emulsions[2] 4 a) Pharmaceutical application of emulsions : Emulsions are used to improve effectiveness by controlling dosage of active ingredients and to provide improved aesthetics for topical drugs such as ointments. Nonionic emulsions are most popular due to their low toxicity, ability to be injected directly into the body and compatibility with many drug ingredients. Cationic emulsions are also used in certain products due to their antimicrobial properties[4]. Multiple emulsions have been formulated as cosmetics, such as a skin moisturizer[2]. Emulsions (macroemulsions and microemulsions) are generally well documented as carriers for hydrophilic and lipophilic drugs[3]. Oils and drugs having objectionable taste or texture can be made more palatable for oral administration by formulating into emulsions. As a result, mineral oilbased laxatives, oil-soluble vitamins, vegetable oils, high-fat nutritive preparations for enteral feeding and certain drugs such as valproic acid are formulated frequently in an oil-in-water (o/w) emulsion form[3]. With topically applied emulsions, the formulation scientist can control the viscosity, appearance and degree of greasiness of cosmetic and dermatologic products. o/w emulsions are most useful as water-washable bases, whereas waterin-oil (w/o) emulsions are used widely for the treatment of dry skin and emollient applications to provide an occlusive effect [3]. Semisolid preparations, such as ointments and creams, represent the dispersions of liquids in solids, which are used topically[3]. Emulsions are also employed in many other clinical applications as radiopaque emulsions and parenteral emulsions and in blood replacement therapy[3]. Water insoluble compounds are orally administered as o/w emulsion with pleasant taste e.g. vitamin A, E, D and K are absorbed more quickly when emulsified [5]. Some therapeutic agents show bioavailability more when given in the form of emulsions e.g. heparin and insulin[5]. Non-absorbable macromolecules are absorbed to small extent when given orally as such insulin and heparin and they may even be digested in stomach. But when these agents are given in emulsified form they are not digested and are fully absorbed[5]. The intravenous fat emulsions are used to supply or deliver isotonic liquids in small amount i.e. volume to provide large amount of energy to the body. The fat emulsions for intravenous nutrition generally contain vegetable oil, a phospholipid and emulsifying agent. The examples are: Intralipid, Lipofundins and Lipofunduns[5]. b) Identification tests for types of emulsion : Since emulsion (o/w or w/o) looks the same in appearance with naked eyes, therefore certain tests have been developed to differentiate between them[2]. It is also important that at least two tests should be performed to draw a final conclusion[6]. Dilution test : In this test the emulsion is diluted either with oil or water. If the emulsion is o/w type and it is diluted with water, it will remain stable as water is 5 the dispersion medium but if it is diluted with oil, the emulsion will break as oil and water are not miscible with each other. Oil in water emulsion can easily be diluted with an aqueous solvent whereas water in oil emulsion can only be diluted with a oily liquid[6]. Fig : Dilution Test[7] Conductivity Test : The basic principle of this test is that water is a good conductor of electricity. Therefore, in case of o/w emulsion, this test will be positive as water is the external phase. In this test, an assembly is used in which a pair of electrodes connected to an electric bulb is dipped into an emulsion. If the emulsion is o/w type, the electric bulb glows[6]. Fig : Conductivity Test [8] Dye Solubility Test : In this test an emulsion is mixed with a water soluble dye (amaranth) and observed under the microscope. If the continuous phase appears red, it means that the emulsion is o/w type as water is in the external phase and the dye will dissolve in it to give color. If the scattered globules appear red and continuous phase colorless, then it is w/o type. Similarly, if an oil soluble dye 6 (Scarlet red C or Sudan III) is added to an emulsion and the continuous phase appears red, then it is w/o emulsion[6]. Fig : Dye Solubility Test [8] Cobalt chloride paper test : Cobalt chloride blue paper turns pink when hydrated[2]. When the filter paper soaked in cobalt chloride solution is dipped in to an emulsion and dried, if it turns from blue to pink, it indicates that the emulsion is o/w type[6]. Fig : Cobalt chloride paper test [9] Fluorescence test : Oil gives fluorescence under UV light, while water does not[2]. If an emulsion on exposure to ultra-violet radiations shows continuous fluorescence under microscope, then it is w/o type and if it shows only spotty fluorescence, then it is o/w type[6]. 7 Fig : Fluorescence test [10] Formation of creaming : Creaming is the upward/downward movement of dispersed droplets of emulsion relative to the continuous phase, due to the density difference between two phases. Upward creaming occurs if the dispersed phase is less dense than the continuous phase. This is normally observed in o/w emulsions. Downward creaming occurs if the dispersed phase is heavier than the continuous phase. Due to gravitational pull, the globules settle down. This is normally observed in w/o emulsions[8]. Fig : Formation of creaming[1] c) Bancroft’s Rule : The Bancroft rule states : "The phase in which an emulsifier is more soluble constitutes the continuous phase[11]." It was named after Wilder Dwight Bancroft, an American physical chemist, who proposed the rule in the 1910s[11]. In all of the typical emulsions, there are tiny particles (dispersed phase) suspended in a liquid (continuous phase). In an oil-in-water emulsion, oil is the dispersed phase, while water is the continuous phase[11]. What the Bancroft rule states is that contrary to common sense, what makes an emulsion oil-in-water or water-in-oil is not the relative percentages of oil or water, but which phase the emulsifier is more soluble in. So even though there may be a formula that's 60% oil and 40% water, if the emulsifier chosen is more soluble in water, it will create an oil-in-water system. It's a very useful rule of thumb for most systems[11]. Emulsifiers/Emulsifying agents are amphiphilic in nature i.e., they have polar & nonpolar 8 group. They stabilize emulsion by preventing/reducing the coalescence of dispersed globules[1]. Fig : Illustration of Bancroft’s Rule[1] The hydrophilic-lipophilic balance of a surfactant is a measure of the degree to which it is hydrophilic or lipophilic, determined by calculating values for the different regions of the molecule, as described by Griffin[12]. The hydrophilic-lipophilic balance (HLB) of a surfactant can be used in order to determine whether it's a good choice for the desired emulsion or not [11]. Fig : HLB Scale[12] In oil-in-water emulsions – use emulsifiers that are more soluble in water than in oil (High HLB surfactants)[11]. 9 In water-in-oil emulsions – use emulsifiers that are more soluble in oil than in water (Low HLB surfactants)[11]. Bancroft’s Rule describes the relationship between the nature of the emulsifying agent/emulsifier and type of emulsion formed[1]. Based on the Bancroft’s rule, it is possible to change an emulsion from O/W type to W/O type by inducing changes in surfactant’s HLB. In other words, phase inversion may be induced[13]. Reference : [1] “Pharmaceutical Emulsion | The Pharmapedia.” http://thepharmapedia.com/pharmaceutical-emulsion/pharmacy-notes/ (accessed Jun. 28, 2021). [2] “PHARMACEUTICAL EMULSIONS - knowledgeabletutorial.” https://www.knowledgeablefact.com/pharmaceutical-emulsions/ (accessed Jun. 28, 2021). [3] “Pharmaceutical Emulsions: An Overview - Pharmapproach.com.” https://www.pharmapproach.com/pharmaceutical-emulsions-an-overview/ (accessed Jun. 28, 2021). [4] “Emulsion - Uses Of Emulsions - Water, Hair, Soluble, and Products - JRank Articles.” https://science.jrank.org/pages/2461/Emulsion-Uses-emulsions.html (accessed Jun. 30, 2021). [5] “SPECIALIZED PHARMACEUTICAL EMULSIONS.” http://infolounge107.blogspot.com/2018/02/specialized-pharmaceuticalemulsions.html (accessed Jun. 30, 2021). [6] “Tests for Identification of Emulsion Types.” https://www.preservearticles.com/education/tests-for-identification-of-emulsiontypes/16986 (accessed Jun. 30, 2021). [7] “Pharmaceutical emulsion - ppt download.” https://slideplayer.com/slide/14041699/ (accessed Jul. 02, 2021). [8] O. Upton, “Pharmaceutical Emulsions - Department of Pharmacy GP (Uttawar),” Techniques, no. Rar 806, pp. 1–5, 2012. [9] “What is the relationship between milk and emulsion? PH ppt download.” https://slideplayer.com/slide/10977922/ (accessed Jun. 30, 2021). 10 [10] “Alfred Martin Lecturer: Dr. Majid R. Feddah - ppt download.” https://slideplayer.com/slide/14230159/ (accessed Jun. 30, 2021). [11] “Bancroft rule - Wikipedia.” https://en.wikipedia.org/wiki/Bancroft_rule#cite_note-4 (accessed Jun. 30, 2021). [12] “Hydrophilic-lipophilic balance - Wikipedia.” https://en.wikipedia.org/wiki/Hydrophilic-lipophilic_balance (accessed Jun. 30, 2021). [13] “Colloid Chemistry,” Colloid Chem., 2019, doi: 10.3390/books978-3-03897-460-4.