Plasticizer class ppt

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Plasticizer in cosmetic technology. UPTU 2nd year BPharm

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  • Plasticizer class ppt

    1. 1. Plasticizers in Cosmetic Technology D.P. Ghosh ASST. Prof. KSOP GHAZIABAD
    2. 2. INTRODUCTION  A plasticizer is a substance which when added to a material, usually a plastic, makes it flexible, resilient and easier to handle.  They are colorless, odorless liquids produced by a simple chemical reaction, where by molecules of water are eliminated from petrochemical products.  They are not just additives. They are major components that determine the physical properties of polymer products.
    3. 3. Introduction 3  Plasticizers are relatively low molecular weight materials which have a capacity to alter the physical properties of a polymer to render it more useful as film forming agents.  The polymers used as film forming agents are relatively brittle in nature at room temperature and pressure.  The function of plasticizer is to make the polymer more pliable and soft and thereby enhancing the flexibility and plasticity to the films.  They modify the physical and mechanical
    4. 4. Cont'd 4  Plasticizer are added in order to reduce the glass transition temperature, this addition of the plasticizer facilitates the thermal stability of the ingredients.  The intensity of particle coalescence and the quality of the resulting final film so formed entirely depends on the type and the concentration of plasticizer added to the coating dispersion.  The efficiency of a plasticizer is intensely related to its chemical structure and the extent and rate of interaction with the polymeric material present in the formulation.  Physicochemical properties of the films mainly
    5. 5. DEFINITION :  A plasticizer or softener is a substance incorporated in a material (usually a plastic) to increase the flexibility, elongation, workability, dispensability.  It may reduce the melt viscosity, lower temperature of second order transition or lower the elastic modulus of the product.  A Plasticizer is a distinct polymer additive.  There are more than 300 different types of plasticizers available . The most commonly used plasticizers are ester like phthalates, adipates and trimellitates.
    6. 6. IDEAL PROPERTIES OF PLASTICIZERS: • It should be flexible resilient and easier to handle. • It should be non volatile with high boiling point. • It should not come out from materials to which it is added. • Plasticizers used for internal purpose should be non toxic. • Lower the tensile strength and softening temperature, of the polymeric materials to which it is added. • Polar with a high Mol. Wt. ester type organic compounds. • Reduce internal friction between polymer chain.
    7. 7. IDEAL PROPERTIES…. • It should reduce the brittleness, improve flow, flexibility, and increase toughness, shear strength, and impart resistance to the polymeric film coating. • It should lower the glass transition temperature of the polymeric film coating. It should reduce the viscosity of materials to which it is added. • it should impart permanent properties such as liability, shock resistance, hand drop. • The main role of the plasticizer is to improve mechanical properties of the polymers by increasing flexibility, decreasing tensile strength and lowering the second order transition temperature.
    8. 8. GLASS TRANSITION TEMPERATURE(Tg): • The temperature at which the glassy polymer becomes rubbery on heating and rubbery polymer reverts to glassy on cooling is called the glass transition temperature. • Polymer in rubbery state are very viscous liquids with relatively high freedom of rotation round the carbon-carbon bonds in the backbone with in the constraint of tetrahedral bond angle. • The temperature is high enough so that most bonds capable of overcoming potential energy barrier against rotation. This rotational freedom results in very flexible chains.
    9. 9. plaPlasticizer 10% plasticizer 20%plasticizer Triethyl citrate Acetyl triethyl citrate Tributyl citrate Acetyl tributyl citrate Triacetin Tg of unplasticized film is 55ºc 34.3 37.0 38.5 38.2 42.2 12.8 17.5 20.5 22.2 27.4 Tg of Eudragit RS 30D(ºc) GLASS TRASITION TEMPERATURE OF EUDRAGIT RS 30 D POLYMERIC FILMS
    10. 10. Why do we need plasticizers?  Almost all the film forming agents or polymers are brittle in nature do to their complex structure.  Most commonly used polymers are the cellulose derivatives or cellulose related compounds like HPMC, MC, EC, Nitrocellulose, HPMCP etc.  These polymers are widely used as film forming materials as they:- Produce transparent films Produce intact films 10
    11. 11. Cont’d They have lower values for water vapor permeability rate. They have lower values for oxygen transmission rates.  They can be structurally modified to achieve sustained release ,like HPMC can be converted to HPMCP for enteric coating.  But due to presence of multiple polymeric strands within a single molecule of polymer makes them brittle. 11
    12. 12. Cont’d  When such a material is applied as a film coat on to tablet a smooth film is not be obtained.  This condition necessitates the addition of plasticizers to the coating/Film forming dispersions.  The addition of plasticizers to polymeric material causes them to diffuse within the polymers and cause polymer deformation and coalescence into homogeneous films.  The effectiveness of plasticizers on polymeric dispersion depends upon polymer compatibility and the permanence of 12
    13. 13. Effect of Plasticizers • Easy melt • Improve flexibility • Increase Softness and Flexibility. • Improve Process ability. • Alters Softening point, Tensile Strength, Elongation at break & Impact.
    14. 14. Mechanism of action 14  The mechanism of action of plasticizers is defined as to interpose between every individual strand of polymer and thereby causing breakdown of polymer -polymer interactions.  The tertiary structure of the polymer is modified into more porous, flexible and with less cohesive structure.  Plasticizers soften and swell the polymer (latex spheres) which aids in overcoming their resistance to deformation.  As a result the plasticized polymer would deform at a lower tensile force as compared to without plasticizer. This enhances the polymer -
    15. 15. Cont'd 15  This effect in turn enhances the film elongation effect.  This interaction to a greater extend depends upon the glass transition temperature of polymers. Glass transition temperature, Tg is the temperature at which hard glassy polymer is converted into a rubbery material.  All polymers have higher glass transition temperatures and addition of plasticizers reduces the glass transition temperature.
    16. 16. MECHANISM....... 16  As plasticizers usually possess relatively long alkyl chains, they have the effect of screening the polymer chains from each other, thereby preventing them from re-forming the chain-chain interactions which give the unplasticized polymer its rigidity.
    17. 17. PLASTICIZATION THEORIES  Lubricity Theory: Plasticizer acts as a lubricant, reducing intermolecular friction between polymer molecules responsible for rigidity of the polymer.  Gel Theory: Polymers are formed by an internal three-dimensional network  Free Volume Theory: Plasticizer lowers the glass transition temperature (Tg) of the polymer.  Mechanistic Theory: Plasticizer molecules are not bound permanently to the polymer molecules form. 17
    18. 18. LUBRICITY THEORY:  A “dry” polymer, a resin without plasticizer, is rigid because friction exists between its chains, binding them into a network.  When the polymer is heated in order to be plasticized, the binding is weakened and the smaller plasticizer molecules are able to slip in between the chains.  When the polymer cools, the plasticizer molecules act as a lubricant between the chains, allowing them to “slip.” GEL THEORY:  The plasticizer molecules break up the polymer-polymer interaction by getting in between the chains and “obscuring” these interaction sites from the polymer molecules.
    19. 19. THE FREE VOLUME THEORY: • The free volume of a polymer can be described as the “empty internal space” available for the movement of the polymer chains.The free volume of a polymer greatly increases when it reaches the glass transition temperature. • At the glass transition temperature, the molecular motion begins to occur, which corresponds to an increase in the free volume of the polymer. • These plasticizer molecules are having low glass transition temperature than the polymer, so that Tg of the resulting mixture will be lower.
    20. 20. Lubricity Theory  Assumes the rigidity of the resin (pure polymer) arises from “intermolecular friction.”  Plasticizer molecules are introduced on heating.  At room temperature, these molecules act as lubricants for the polymer chains.
    21. 21. Gel Theory  Resin-resin interactions occur at “centers of attachment.”  Plasticizer molecules break these interactions and masks the centers from each other, preventing re-formation.  This theory is not sufficient to describe interaction– should be combined with Lubricity Theory.
    22. 22. Free-Volume Theory  Free volume: “internal space” available in the polymer for the chains to move.  This volume increases sharply at the glass transition temperature, Tg.  Plasticizer is meant to decrease the glass transition temperature, imparting increased flexibility to polymer at room temperature.
    23. 23. TYPES OF PLASTICIZERS These are two types  Internal plasticizers  External plasticizers:  Primary plasticizers  Secondary plasticizers
    24. 24. CLASSIFICATION  Majority of plasticizers are Organic Esters. 24 According to technique of Plasticization External Internal Not physically bound to polymer & can evaporate, migrate or exude from polymer. Group constituting a part of a basic polymer chain, which may incorporate bet. chain
    25. 25. INTERNAL PLASTICIZERS: • A rigid polymer may be internally plasticized by chemically modifying the polymer or monomer so that flexibility polymer is increased. • The process by which Tg of rigid polyvinylchloride is lowered through copolymerization, is called internal plasticization. EXTERNAL PLASTICIZERS: • These are high boiling liquids, non volatile and having low vapor pressure. • They must soluble in polymer and reduce the Tg of polymer below room temperature rendering it softer and flexible • They acts as lubricants between the polymer chains, facilitating slippage of chain under stress.
    26. 26. Types of Plasticizer (I)  Internal vs. External  Internal plasticization occurs via chemical interactions.  Copolymerization is one type of internal plasticization.  External plasticization occurs via physical interactions.  External is the most common: cost, ease of processing.
    27. 27. CLASSIFICATION  Other 27 Conventionally classified as SecondaryPrimary Sufficient level of compatibility to be used give desirable effect. directly interact with chain. Limited compatibility & can exude if used alone. Incorporate with primary plasticizer.
    28. 28. PRIMARY PLASTICIZERS: Also called as chemical plasticizers, when added to polymer, will cause the properties of elongation and softness of the polymer to be increased. SECONDARY PLASTICIZERS: Also called as plasticizing oils. They are not used alone but when combined with primary plasticizers will enhance the plasticizing performance of the primary plasticizer.
    29. 29. Types of Plasticizer (II)  Primary vs. Secondary  Primary Plasticizer affects resin properties.  Secondary is a “Plasticizer- plasticizer”: used to increase the effectiveness of the primary plasticizer.
    30. 30. Types of Plasticizers • Primary – These are highly compatible with PVC and can be used alone. • e.g. – Phthalates – Di-Octyl Phthalate (DOP), Di Iso Octyl Phthalate (DIOP) – Phosphates – Tricresyl Phosphate (TCP), – Sebacates, – Adipates.
    31. 31. Types of Plasticizers • Secondary – These are less compatible with resin & and are usually employed together with primary plasticizers. • e.g. – Di Octyl Sebacate (DOS) – Adipic Acid Polyesters – Epoxidised oil.
    32. 32. SELECTION CRITERIA  Choice of plasticizer depends upon the properties required in final product, the application technology used to make it !!  Prize boundaries present for product process.  Stability in processing & service condition.  Compatibility & ease of mixing.  Toxicity. 32
    33. 33. PLASTICIZER EFFICIENCY..  The measure of concentration of plasticizer require to improve a specifies softness of the polymer.  Plasticizer efficiency increases as carbon number of alcohol chain decreases.  For phthalates, BBP>DIHP>DOP>DINP>DIDP  Linear plasticizer is more efficient. 33
    34. 34. Plasticization in Cosmetics  Polymers used in cosmetics are generally amorphous in nature.  Unfortunately Glass transition temperature of most of the polymers are in excess of conditions exposed for the cosmetic manufacturing.  Thus one needs to incorporate plasticizer basically for two main reasons:- 1. Modification of polymer properties so as to impart flexibility which reduces the Tg of amorphous polymer. 2. To facilitate the processing of dosage form at substantial temperature conditions to protect the integrity of active ingredient.
    35. 35. Timeline (history) First Plasticiz er 1860 1930 Phthalate s Introduce d 1980’s DEHP Declared Carcinogeni c 2001 IARC Re- classifies DEHP as non- carcinogenic 1998 European Parliament calls for alternatives to phthalates
    36. 36. Limitations 36 (A) LEACHING EFFECT-  The major trouble encountered during the plasticizing of polymers is the leaching of the plasticizer from the film.  This leaching effect of Plasticizer is dependent on the type and concentration of dissolution medium.  This eventually results in drastic alteration of film properties.  This tendency of plasticizers can be well demonstrated from the In vitro dissolution studies with cast films of Eudragit® RS/RL had leached out the water-soluble plasticizers when the
    37. 37. Cont’d 37  Permanence is an attribute taken in consideration as loss of plasticizer during storage of plasticizers which in turn can hamper integrity of coated tablets.  The mechanism by which permanence occurs is said to be migration via diffusion process.  The molecular size and shape of the plasticizer are highly important as small molecules migrate faster than large ones. Also linear molecules migrate faster than bulky, branched ones.  The highly solvating ones that produce an open gel structure migrate at a faster rate.
    38. 38. Cont’d 38  Volatility was found to be one of the major cause.  Thus permanence due to leaching tendency of plasticizers can be controlled by diffusion control.  This diffusion of plasticizer can be controlled by incorporating a more non volatile plasticizer or switching to a higher molecular weight plasticizer.
    39. 39. PLASTICIZERS IN FILM COATING: The commonly used plasticizers can be categorized into three groups: 1. Polyols: (a) Glycerol (glycerin); (b) Propylene glycol; s(c) Polyethylene glycols PEG (generally the 200–6000 grades). 2. Organic esters: (a) Phthalate esters (diethyl, dibutyl); (b) Dibutyl sebacete; (c) Citrate esters (triethyl, acetyl triethyl, acetyl tributyl); (d) Triacetin.  3. Oils/ glycerides: (a) Castor oil; (b) Acetylated monoglycerides; (c) Fractionated coconut oil
    40. 40. TYPES OF PLASTICIZERS: • Phthalates • Adipates • Citrates • Phosphate esters • Polymerics • Esters of glycol and polyhydric alcohols • Sebacate nad azelate esters • Secondary plasticizers • Trimellitates
    41. 41. Plasticizers: Classification Class Examples Polyhydric alcohols Propylene glycol Glycerol Polyethylene glycol Acetate esters Glyceryl triacetate Triethyl citrate Acetyl triethyl citrate Phthalate esters Diethyl phthalate Glycerides Acetylated monoglycerides Oils Castor and mineral oil.
    42. 42. 42
    43. 43. Classification of plasticizers Depending on their properties they can be classified as:-  Polyols Glycerol Propylene glycol PEG 200-6000 grades.  Organic esters Triacetin, Diethyl phthalate (DEP), Dibutyl phthalate (DBP) and Tributyl citrate (TBC) 43
    44. 44. Cont’d  Oils/ glycerides Castor oil Fractionated coconut oil Acetylated monoglycerides.  Newer Plasticizers – DBS (Dibutyl Sebacate).  Can be used for the very plasticizing effect in both aqueous and solvent based pharmaceutical coatings.  Under this category both the hydrophilic as well 44
    45. 45. Properties of commonly used plasticizers. (A) PEGs  These are hydrophilic substances and soluble in water.  In the conventional film coating the solid grades of PEGs are used alone as hydrophilic plasticizers.  Rate of release of water soluble drugs decreases with increase in the molecular weight of PEGs.  The PEG with molecular weight of 6000 and above decreases plasticizing effect and 45
    46. 46. PHTHALATES 46  Most widely use as plasticizer.  Phthalates accounts 92% of all plasticizers.  A Phthalate ester derived from phthalic acid by an esterification reaction.  Properties: Colorless Oily liquid ( like vegetable oil) Ester odor, High boiling point, Inert and very stable over long periods
    47. 47. PHTHALATES: • Both ortho-phthalic and terephthalic acids are used to react with alcohol to produce phthalate esters • Alcohol used in the range from methanol(c1 up to c17.) • When added to vinyl, phthalate molecules are tightly bound up between the long vinyl molecules, making them slip and slide against each other without sacrificing strength. ADVANTAGES: • Migration is less • Readily biodegradable • Does not cause any harm to body.
    48. 48. Cont’d (C) DEP- Di ethyl Phthalate.  Used both as a solvent and plasticizer.  Non toxic, non irritant.  DEP is used as a plasticizer in film coating of tablets , beads and granules at a concentration of 10-30% W/W of polymers.  Its is insoluble in water, soluble in ethanol, ether and orgainc solvents.  It is volatile in nature. 48
    49. 49. Cont’d (D) DBP- Dibutyl Phthalate.  Also known as kodaflex DBP.  Very soluble in acetone, benzene, ethanol, ether and soluble in water.  Is principally used as a plasticizer.  But it has limited compatibility with the cellulose acetate polymers. 49
    50. 50. A) DI-2-ETHYLHEXYL PHTHALATE:  Also known as di-octyl phthalate.  It is considered as the industry standard.  It is phthalate ester of alcohol 2-ethylhexanol. Advantages  Low cost  Posses reasonable plasticizing efficiency, fusion rate , viscosity Disadvantages:  It is toxic
    51. 51. DOP/DEHP 51  Primary use as plasticizer.  Insoluble in water, Boiling point: 386.9oc,Density: 0.9732 g/L, Molecular weight: 390.5618 g/mol.  Production: Phthalic anhydride with 2-ehaxenol: C6H4(CO)2O + 2 C8H17OH → C6H4(CO2 C8H17)2 + H2O  Used in medical devices ,Toys, Pacifiers, Vinyl Upholstery, Food containers, Table cloths, Shower curtains.
    52. 52. B) DIISODECYL PHTHALATE(DIDP) AND DIISONONYL PHTHALATE (DINP) :  These are prepared from oxo alcohols of carbon c9 and c10  These are used for heat resistant electrical cards, leather for car interiors and PVC flooring in concentration of 25 to 50%. ADIPATES:  Adipates are prepared from alcohols in the c8 to c10 range.  They are having improved low temperature performance and low viscosity.  They are highly volatile, having high migration rate and are high priced.
    53. 53. DINP 53  Mixture of chemical compounds consisting of various isononyl esters & phthalic acid.  Properties :Insoluble in H2O,Soluble in most organic solvents, Boiling point: 250Density: 0.98g/cc, Molecular weight: 418.6 g/mol.  Use in Replacing DEHP in toys when initially determined to be carcinogenic.
    54. 54. DIDP 54  Mixture of compounds derived from the esterification of phthalic acid & isomeric decyl alcohol.  Properties: density:0.96g/cc, melting point: -50, boiling point: 250-257c at 0.5KPa.  Uses in plastisol application, provides good initial viscosities & excellent viscosity stability.
    55. 55. CITRATES:  These include triethyl citrate, acetyl triethyl citrate, tributyl citrate and acetyl tribuyl citrate  Tri butyl citrate is heat stable and does not discolour when processed in compound resins.  These esters used in electrical coatings, food industry, hair sprays and inks. PHOSPHATES:  They show good compatibility with PVC.  They are having good low temperature performance, migration resistance and improved fire retardency relative to phthalates.
    56. 56. Cont’d (E) Triacetin  Also known as Triethyl glycerin or glycerol triacetate.  Used as both plasticizer and a solvent.  Its an hydrophilic plasticizers.  This plasticizer is suitable for both aqueous and solvent based polymeric coating of tablets, granules and beads in concentration of 10-35% by weight of polymer.  Miscible with water as well as in ether, ethanol, 56
    57. 57. Cont’d (F) TEC- Triethyl Citrate.  It is a citric acid ethyl esters.  Also known as Citroflex 2.  Its is principally used as plasticizer.  It is effectively used in aqueous based coating in Oral sustained or enteric coated tablets .  Miscible with water. 57
    58. 58. SEBACATES & ADIPATES 58  Dibutyl Sebacate is an organic chemical , a dibutyl ester of sebacic acid.  Properties: density: 0.94g/cc, boiling point:344.5c , melting point:-10c, flash point: 178c.  Used in food packaging industry, in plastics used for medical devices, and for pharmaceutical applications,
    59. 59. TRIMELLITATE PLASTICIZERS - 59  Synthesized using one mole of trimellitic anhydride and 3 moles of an alcohol. The third alkyl group, compared to phthalates, contributes higher molecular weight (low diffusivity);the third ester group contributes sufficient polarity to enhance compatibility with PVC. Tri (2-ethylhexyl) Trimellitate
    60. 60. FATTY ACID ESTERS  Esters of fatty acids & monocarboxylic acids can be used as viscosities depressant for PVC pastes & also as secondary plasticizers for plasticized PVC.  Present in liquid form.  Stearic acid esters are used as plasticizers & processing agent for various plastics & also as lubricants for PS. 60
    61. 61. OLIGOMERIC/POLYMERIC PLASTICIZER  These extend the life of PVC products considerably  They reduce migration, extraction & volatility.  In these adipates are generally used in mixture with other plasticizer to increase plasticization & improve low temp. Properties.  Epoxied plasticizer (soybean oil & linseed oil) are used as stabilizing plasticizer offering properties of migration resistance in PVC compounds. 61
    62. 62. POLYMERICS: • These are produced by reacting a dibasic carboxylic acids with one or more glycols. • These are manufactured in a wide range of viscosities. With increasing viscosity, handling become more difficult. • The optimum viscosities of some acids are adipates-5600 cps, glutarates-12000 cps. ESTERS OF GLYCOLS AND POLYHYDRIC ALCOHOLS: • polyhydric alcohols are propylene glycol, glycerol, polyethylene glycol and Esters of glycols are glyceryl triacetate, tri ethyl citrate. • These are water soluble and used in aqueous film coatings.
    63. 63. SECONDARY PLASTICIZERS: • They are also known as extenders. • The majority of these plasticizers include chlorinated paraffin's, which are hydrocarbons chlorinated to a level of 30- 70%. • The fire retardency and viscosity increases with chlorine content. • Other materials used are epoxidised soya bean oil and epoxidised linseed oil. • They acts as lubricants to pvc due to their epoxy content.
    64. 64. TRIMELLITATES: • Common esters in these family are tris-2 ethylhexyltrimellitate,L810TM, an ester of mixed c8 and c10 linear alcohols. Advantages: • Low volatility • Low migration rate. SEBACATE AND AZELATE ESTERS: • Di-2-ethylhexyl sebacate (DOS) and di-2-ethylhexyl azelate (DOZ) are the most common members of this group, but Diisodecyl Sebacate (DIDS) is also used. They give superior low temperature performance than adipates.
    65. 65. Cont’d (B) DBS- Dibutyl Sebacate.  These are esters of n-butanol and saturated dibasic acids.  Principally used as plasticizers in film coating.  For film coating as a plasticizer, DBS is used in 10-30% concentration by weight of polymer.  Insoluble in water but soluble in ethanol, mineral oil etc.  Quite suitable for solvent based coating dispersions. 65
    66. 66. Classification on basis of water solubility. (A) Water soluble PEG TEC Triacetin (B) Water insoluble are DEP DBS DBP ATEC –Acetyl-triethyl-citrate. 66
    67. 67. Cont’d  Water soluble plasticizers make solutions whereas the insoluble plasticizers are emulsified into dispersions.  With insoluble plasticizers, their dispersion is described as a 3 phase systems containing water phase, polymer phase and plasticizer emulsified droplets.  The rate and the extend of plasticizers uptake by the colloidal polymers was explained by conducting the effect of type and concentrations of plasticizers on Aquacoat and the plasticized films so formed were characterised by HPLC. 67
    68. 68. Cont’d  Whereas the water insoluble plasticizers i.e. DBS partitioned about 90% or more into the polymer phase. And the rest form was present as emulsified droplets.  Under such conditions when the plasticized droplet containing coating dispersions are sprayed onto the tablets they generate rough, brittle and uneven films which potentially alters mechanical properties and release profile of drug from the coated dosage forms.  The rate of uptake of plasticizers by the polymers is a function of plasticizing time. But in case of water soluble plasticizers like triacetin or TEC uptake is not affected by the 68
    69. 69. Cont’d  But for water insoluble plasticizers like DBS incomplete plasticizing is observed even after long plasticization time for ethylcellulose latex.  To overcome this undesired effect we carry out an additional step called “Curing Step” . 69
    70. 70. Conclusion  Plasticizers play a very significant role on mechanical properties, permeability of films and release of drug from the coated products.  They do enhance flexibity and plasticity of films.  Therefore, the selection of a plasticizer for a film- coating formulation is very important in the process development and optimization of a coated dosage form.  Curing conditions can facilitate the uniform distribution of plasticizers.  Therefore, one needs to strike a balance between the desired and undesired effects of the plasticizer and optimize its concentration in the 70
    71. 71. CONCLUSION:  Plasticizers are necessary for almost all polymers that are currently used for film coating of tablets and beads. Plasticizers reduce the brittleness, improves flow, impart flexibility, and increase flexibility, and increase toughness, strength, tear resistance of polymers.  Although there are many plasticizers used in chemical industry, only a few plasticizers have been approved for pharmaceutical applications due to environmental and human health concerns attributed to plasticizers toxicity.
    72. 72. References 1. Harry R.G., Reiger M.M., Harry’s Cosmeticology, Chemical publishing company. Newyork 2. Balsam M.S., Sagarin E., Cosmetics: Science and Technology. Wiley Interscience. Newyork 3. Rao Y.M., Shayeda, Cosmeceuticals, Pharma Med Press. Hyderabad 4. Paye M., Basel A.O., Maibach H.I., Handbook of Cosmetic Science & Technology, Informa Healthcare. Newyork 5. Sharma P.P., Cosmetics Formulation, Manufacturing and Quality control, Vandana Publication Pvt. Ltd. Delhi 6. Poucher W.A., Butler H., Poucher’s Perfumes, Cosmetic & Soaps, Springer India Pvt. Ltd. New Delhi. 7. Nanda S., Nanda A., Cosmetic Technology, Birla Publication, Delhi. 8. SCCS's Notes of Guidance for the Testing of Cosmetic Ingredients and their Safety Evaluation, 7th Revision. European Commission. 9. Indian Pharmacopoeia 2014(7th edition), Ministry of Health and Family Welfare, Published by Govt. of India.
    73. 73. THANK YOU 73

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