PHARMACEUTICAL AEROSOL Definition Advantages Components of aerosols description of components of aerosol formulation of pharmaceutical aerosols manufacturing of pharmaecutical aerosls

evaluation parameters of aerosls

Slide 1: Amit M Gupta Lecturer, Agnihotri College of Pharmacy, Wardha Emulsion Emulsion : Emulsion Definition Applications Classification Theory of emulsificat ion Stability of emulsion Preservation of emulsion Emulsion preparation Nascent method Dry gum Wet gum Incorporation of drugs into emulsion Microemulsion Emulsion : Emulsion A . Two immisicble liquids, not emulsified; B . An emulsion of P hase B dispersed in Phase A; C . The unstable emulsion progressively separates; D . The (purple) surfactant positions itself on the interfaces between Phase A and P hase B, stabilizing the emulsion An emulsion is a thermodynamically unstable sys tem consisting of at least two immiscible liquid phases, one of which is dispers ed as globules in the other liquid phase, stabilized by the presence of an emuls ifying agent. Pharmaceutical application of emulsions : Pharmaceutical application of emulsion s O/W emulsion is convenient for oral dosing To cover unpleasant taste To increa se oral absorption I.V. O/W, if oral o/w not possible (RES uptake) External use (topical cream) A broad-spectrum antifungal agent administered orally to treat a variety of fungal infections. Emulsion types : Emulsion types Types Oil-in-water (o/w) Water-in-oil (w/o) Oilin-water-in-oil (o/w/o) Water-in-oil-in-water (w/o/w) Determination of o/w or w/ o Water soluble dye (e.g., methylene blue) Dilution of emulsions Conduction of c urrent Theory of emulsification : Theory of emulsification Change from A to B will sign ificantly increase of the surface area of phase. e.g., if 1 cm3 of mineral oil i s dispersed into globules having diameter of 0.01 mm in 1 cm3 of water, how much will be the surface area increased. The surface area will become 600 m2 (greate r than a basketball court); the surface free energy will increase by 8 calories. Therefore, emulsions are thermodynamically unstable, and the droplets have the tendency to coalesce. Emulsifying agents are needed to decrease the surface tens ion and to stabilize the droplets.

Classification of emulsifying agents : Classification of emulsifying agents Surf ace active agents (monomolecular film) Hydrophilic colloids (multimolecular film ) Finely divided solid particles (Particulate film) Monomolecular adsorption : Monomolecular adsorption Rule of Bancroft: The type o f the emulsion is a function of the relative solubility of the surfactant, the p hase in which it is more soluble being the continuous phase. Multimolecular adsorption and film formation : Multimolecular adsorption and fil m formation 1. Hydrated lyophilic colloids (hydrocolloids) providing a protectiv e sheath around the droplets imparting a charge to the dispersed droplets (so th at they repel each other) swelling to increase the viscosity of the system (so t hat droplets are less likely to merge) 2. Classification of hydrocolloids vegeta ble derivatives, e.g., acacia, tragacanth, agar, pectin, lecithin animal derivat ives, e.g., gelatin, lanolin, cholesterol Semi-synthetic agents, e.g., methylcel lulose, carboxymethylcellulose Synthetic agents, e.g., carbomers (PEG and acryli c acid) Solid particle adsorption : Solid particle adsorption Description: Finely divide d solid particles that are wetted to some degree by both oil and water can act a s emulsifying agents. This results from their being concentrated at the interfac e, where they produce a particulate film around the dispersed droplets to preven t coalescence. Example of agents: bentonite (Al2O3.4SiO2.H2O), veegum (Magnesium Aluminum Silicate), hectorite, magnesium hydroxide, aluminum hydroxide and magn esium trisilicate Auxiliary Emulsifying Agents A variety of fatty acids (e.g., s tearic acid), fatty alcohols (e.g., stearyl or cetyl alcohol), and fatty esters (e.g., glyceryl monostearate) serve to stabilize emulsions through their ability to thicken the emulsion. Because these agents have only weak emulsifying proper ties, they are always use in combination with other emulsifiers. Auxiliary emulsifying agents : Auxiliary emulsifying agents Auxiliary (secondary ) emulsifying agents include those compounds that are normally incapable themsel ves of forming stable emulsion. Their main values lies in their ability to funct ion as thickening agents and thereby help stabilize the emulsion. Physical stability of emulsion : Physical stability of emulsion Creaming Creamin g is the upward movement of dispersed droplets of emulsion relative to the conti nuous phase (due to the density difference between two phases) Stoke s law: dx/dt = d2 (?i-?e)g/18h dx/dt = rate of setting D = diameter of particles ? = density of particles and medium g = gravitational constant h = viscosity of medium Physical stability of emulsion : Physical stability of emulsion Breaking, coales cence, aggregation Breaking is the destroying of the film surrounding the partic les. Coalescence is the process by which emulsified particles merge with each to form large particles. Aggregation: dispersed particles come together but do not fuse. The major fact preventing coalescence is the mechanical strength of the i nterfacial film. Physical stability of emulsion : Physical stability of emulsion Phase inversion An emulsion is said to invert when it changes from an o/w to w/o or vice versa. Addition of electrolyte Addition of CaCl2 into o/w emulsion formed by sodium ste

arate can be inverted to w/o. Changing the phase:volume ratio Preservation of emulsions : Preservation of emulsions Growth of microorganisms i n emulsions Preservatives should be in aqueous phase. Preservatives should be in unionized state to penetrate the bacteria Preservatives must not bind to other components of the emulsion Methods of emulsion preparation : Methods of emulsion preparation Continental or dry gum method Wet gum method Bottle or Forbes bottle method Auxiliary method I n situ soap method Calcium soaps: w/o emulsions contain oils such as oleic acid, in combination with lime water (calcium hydroxide solution, USP). Prepared by m ixing equal volumes of oil and lime water. Nascent soap : Nascent soap Oil phase: olive oil/oleic acid; olive oil may be re placed by other oils, but oleic acid must be added Lime water: Ca(OH)2 should be freshly prepared. Equal volume of oil and lime water The emulsion formed is w/o or o/w? Method of preparation: Bottle method: Mortar method: when the formulati on contains solid insoluble such as zinc oxide and calamine. Dry gum method : Dry gum method The continental method is used to prepare the in itial or primary emulsion from oil, water, and a hydrocolloid or "gum" type emul sifier (usually acacia). The primary emulsion, or emulsion nucleus, is formed fr om 4 parts oil, 2 parts water, and 1 part emulsifier. The 4 parts oil and 1 part emulsifier represent their total amounts for the final emulsion. In a mortar, t he 1 part gum (e.g., acacia) is levigated with the 4 parts oil until the powder is thoroughly wetted; then the 2 parts water are added all at once, and the mixt ure is vigorously and continually triturated until the primary emulsion formed i s creamy white. Additional water or aqueous solutions may be incorporated after the primary emulsion is formed. Solid substances (e.g., active ingredients, pres ervatives, color, flavors) are generally dissolved and added as a solution to th e primary emulsion. Oil soluble substance, in small amounts, may be incorporated directly into the primary emulsion. Any substance which might reduce the physic al stability of the emulsion, such as alcohol (which may precipitate the gum) sh ould be added as near to the end of the process as possible to avoid breaking th e emulsion. When all agents have been incorporated, the emulsion should be trans ferred to a calibrated vessel, brought to final volume with water, then homogeni zed or blended to ensure uniform distribution of ingredients. Preparing emulsion by dry gum method : Preparing emulsion by dry gum method Cod liver oil 50 mL Acacia 12.5 g Syrup 10 mL Flavor oil 0.4 mL Purified water, qs a d 100 mL Accurately weigh or measure each ingredient Place cod liver oil in dry mortar Add acacia and give it a very quick mix Add 25 mL of water and immediatel y triturate to form the thick, white, homogenous primary emulsion Add the flavor and mix Add syrup and mix Add sufficient water to total 100 mL Wet gum method : Wet gum method In this method, the proportions of oil, water, a nd emulsifier are the same (4:2:1), but the order and techniques of mixing are d ifferent. The 1 part gum is triturated with 2 parts water to form a mucilage; th en the 4 parts oil is added slowly, in portions, while triturating. After all th e oil is added, the mixture is triturated for several minutes to form the primar y emulsion. Then other ingredients may be added as in the continental method. Ge nerally speaking, the English method is more difficult to perform successfully, especially with more viscous oils, but may result in a more stable emulsion.

Bottle method : Bottle method This method may be used to prepare emulsions of vo latile oils, or oleaginous substances of very low viscosities. This method is a variation of the dry gum method. One part powdered acacia (or other gum) is plac ed in a dry bottle and four parts oil are added. The bottle is capped and thorou ghly shaken. To this, the required volume of water is added all at once, and the mixture is shaken thoroughly until the primary emulsion forms. It is important to minimize the initial amount of time the gum and oil are mixed. The gum will t end to imbibe the oil, and will become more waterproof. Auxiliary method : Auxiliary method An emulsion prepared by other methods can al so usually be improved by passing it through a hand homogenizer, which forces th e emulsion through a very small orifice, reducing the dispersed droplet size to about 5 microns or less. Incorporation of medicinal agents : Incorporation of medicinal agents Addition o f drug during emulsion formation Addition of drugs to a preformed emulsion 1. Ad dition of oleaginous materials into a w/o emulsion 2. Addition of oleaginous mat erials to an o/w emulsion 3. Addition of water soluble materials to a w/o emulsi on 4. Addition of water soluble materials to an o/w emulsion Microemulsion : Microemulsion Microemulsions are thermodynamically stable, optic ally transparent, isotropic mixtures of a biophasic oil-water system stabilized with surfactants. Pharmaceutical applications of microemulsions : Pharmaceutical applications of m icroemulsions Increase bioavailability of drugs poorly soluble in water Topical drug delivery systems Preparation of nanoparticles from microemulsion precursors : Preparation of nano particles from microemulsion precursors Slide 30: THANK YOU,,,,,,,