An overview peg & poloxamer
- 1. An Overview: PEG & Poloxamer Presented By: Mayur N. Pandya 14MPH114 M.Pharm Sem-1 IPNU Guided By: Dr. Tejal A. Mehta HOD Dept. of Pharmaceutics IPNU
- 2. CONTENTS PEG Introduction Characteristics Manufacturing Method Merit & Demerits Functional Category Applications Poloxamer Introduction Characteristics Manufacturing Method Functional Category Biological Effects Applications
- 4. Introduction • PEG (Poly Ethylene Glycol) is most used excipient as polymer for Formulations in Pharmaceutical field. • PEG is a polyether compound with many applications from industrial manufacturing to medicine. • The ability of PEG to influence the pharmacokinetic properties of drugs and drug carriers is currently utilized in a wide variety of established and emerging applications in pharmaceutics.
- 5. • PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight. • The Structure of PEG is H-(O-CH2-CH2)n-OH here n indicates number of EO(polyethylene units). • Generally, variable PEG Commercial grades denoted its molecular weight. E.g. PEG 400 PEG 800 PEG 200
- 6. • Nonproprietry Names BP: Macrogols JP: Macrogol 400 Macrogol 1500 Macrogol 4000 Macrogol 6000 Macrogol 20000 PhEur: Macrogols USP-NF: Polyethylene Glycol • Chemical Name α-Hydro-o-hydroxypoly(oxy-1,2-ethanediyl)
- 7. • Synonyms Carbowax Carbowax Sentry Lipoxol Lutrol E Macrogola Pluriol E • Structural Formula
- 8. Manufacturing Method • In Pharmaceutical industry, PEGs are manufactured by polymerization of ethylene oxide(EO) with either water, mono ethylene glycol or diethylene glycol as starting material, under alkaline catalysis. • After the desired molecular weight is reached (usually checked by viscosity measurements as in-process control) the reaction is terminated by neutralizing the catalyst with acid. • Normally lactic acid is used, but also acetic acid or others can be found.
- 9. Characteristics • Appearance Polyethylene glycol grades 200–600 are liquids grades 1000 and above are solids at ambient temperatures. PEG 600 can occur as a solid at ambient temperatures. Solid grades (PEG>1000) are white or off-white in color, and range in consistency from pastes to waxy flakes. They have a faint, sweet odor. Grades of PEG 6000 and above are available as freeflowing milled powders. Liquid grades (PEG 200–600) occur as clear, colorless or slightly yellow-colored, viscous liquids. They have a slight but characteristic odor and a bitter, slightly burning taste.
- 10. • Moisture Content Liquid polyethylene glycols are very hygroscopic, although hygroscopicity decreases with increasing molecular weight. Solid grades, e.g. PEG 4000 and above, are not hygroscopic. • Surface Tension Approximately 44 dynes/cm (44mN/m) for liquid polyethylene glycols. Approximately 55 dynes/cm (55mN/m) for 10% w/v aqueous solution of solid polyethylene glycol.
- 11. • Solubility All grades of polyethylene glycol are soluble in water and miscible in all proportions with other polyethylene glycols(after melting, if necessary). Aqueous solutions of higher molecular-weight grades may form gels. Liquid polyethylene glycols are soluble in acetone, alcohols, benzene, glycerin, and glycols. Solid polyethylene glycols are soluble in acetone, dichloromethane, ethanol (95%), and methanol; they are slightlysoluble in aliphatic hydrocarbons and ether, but insoluble in fats,fixed oils, and mineral oil. • Density 1.11–1.14 g/cm3 at 25°C for liquid PEGs. 1.15–1.21 g/cm3 at 25°C for solid PEGs.
- 12. • Flash Point 182°C for PEG 200 213°C for PEG 300 238°C for PEG 400 250°C for PEG 600 • Melting Point 37–40°C for PEG 1000 44–48°C for PEG 1500 55–63°C for PEG 6000 60–63°C for PEG 8000 60–63°C for PEG 20000
- 13. • Stability Polyethylene glycols are chemically stable in air and in solution, although grades with a molecular weight less than 2000 are hygroscopic. Polyethylene glycols do not support microbial growth, and they do not become rancid. Polyethylene glycols and aqueous polyethylene glycol solutions can be sterilized by autoclaving, filtration, or gamma irradiation. • Storage Polyethylene glycols should be stored in well-closed containers in a cool, dry place. Stainless steel, aluminum, glass, or lined steel containers are preferred for the storage of liquid grade
- 14. Merits • Polyethylene glycols are stable, hydrophilic substances that are essentially nonirritant to the skin. • Polyethylene glycols are water-soluble and are easily removed from the skin by washing, making them useful as ointment bases. • Mixtures of polyethylene glycols can be used as suppository bases for which they have many advantages over fats. For example, the melting point of the suppository can be made higher towithstand exposure to warmer climates. • The physical stability on storage is Better. • Suppositories are readily miscible with rectal fluids.
- 15. Demerits • They are chemically more reactive than fats greater care is needed in processing to avoid inelegant contraction holes in the suppositories • The rate of release of water-soluble medications decreases with the increasing molecular weight of the polyethylene glycol • Polyethylene glycols tend to be more irritating to mucous membranes than fats.
- 16. Functional Category • Ointment Base • Plasticizer • Solvent • Suppository Base • Tablet • Capsule Lubricant
- 17. Applications • Polyethylene glycols (PEGs) are widely used in a variety of pharmaceutical formulations, including parenteral, topical, ophthalmic, oral, and rectal preparations. • Polyethylene glycol has been used experimentally in biodegradable polymeric matrices used in controlled-release systems. • Polyethylene glycols have been used in the preparation of urethane hydrogels, which are used as controlled-release agents.
- 18. • PEG grafted with poly(methacrylic acid) have been used as bioadhesive controlled drug delivery formulations. • It can be used alone for the film-coating of tablets or can be useful as hydrophilic polishing materials. • Animal studies have also been performed using polyethylene glycols as solvents for steroids in osmotic pumps. • Polyethylene glycols are useful as plasticizers in microencapsulated products to avoid rupture of the coating film when the microcapsules are compressed into tablets.
- 19. POLOXAMER
- 20. INTRODUCTION • Poloxamers are Non-ionic triblock co-polymers comoposed of a Central hydrophobic chain of Polyoxypropylene flanked by two hydrophobic chains of polyoxyethylene. • Poloxamers are often considered as “Functional Excipients” because they are essential components and play an important role in the Formulation.
- 21. • Poloxamers are synthetic triblock Co-polymers with the following general structure formula
- 22. • Non-proprietary Names BP : Poloxamers PhEur : Poloxamera USPNF : Poloxamer • Synonyms Lutrol Monolan Polyethylene Propylene Glycol Copolymer
- 23. Commercial Grades Non-Proprietry Name Commercial Grades Poloxamer 124 L-44 Poloxamer 184 L-64 Poloxamer 185 P-65 Poloxamer 188 F-68 Poloxamer 237 F-87 Poloxamer 338 F-108 Poloxamer 407 F-127
- 24. Characteristics The Character of each poloxamer in terms of : Is Determined By The Chain Length Of the Polyethylene (EO) Units AND Polyoxypropylene (PO) Units Molecular Wt. Appearance Hydrophobici ty/Hydrophilici ty Solubility
- 25. • Appearance Polxamer 124: Colourless or Almost colourless liquid Poloxamer 188, 237, 338, 407: White or almost white, waxy powder, microbeads or flakes. • HLB Value: 0.5-30. • Flowability: Solid Poloxamers are free flowing.
- 26. • Solubility Poloxamer 124, 237, 338, 407: Very Soluble in water and in ethanol (96%), Practically insoluble in light petroleum (50-70°C) Poloxamer 188: Soluble in Water and in Ethanol (96%) • pH(Aqueous Solution): 5.0-7.5
- 27. • Melting Point Non-Proprietry Name Melting Point (°C) Poloxamer 124 16 Poloxamer 188 52-57 Poloxamer 237 49 Poloxamer 338 57 Poloxamer 407 52-57
- 28. • Moisture Content Poloxamers generally contain less than 0.5% w/w water and are Hygro-scopic only at relative humidity greater than 80% • Density 1.06 g/cm3 at 25°C • Flash Point 260°C
- 29. • Incompatibilities Depending on the relative concentrations E.g. Poloxamer 188 is Incompatible with phenols and parabens. • Storage Stored in a well closed container in a cool, dry place.
- 30. Manufacturing Method • Poloxamer polymers are prepared by reacting propylene oxide with propylene glycol to form polyoxypropylene glycol. • Ethylene Oxide is then added to form the block co-polymer. • All Poloxamer are chemically similar in composition, differing only in the relative amounts of propylene and ethylene oxides.
- 31. Functional Category • Dispersing Agent • Emulsifying Agent • Solubilizing Agent • Tablet Lubricant • Wetting Agent
- 32. Biological Effects • Researchers have recently shown that some of these polymers, originally inert carrier molecules have a very real effect on biological systems independently of the drug they are transporting • The Poloxamers have been shown to incorporate cellular membranes affecting the microviscosity of the membranes and increase drug transportation Effect On Multi Drug Resistant Cancer Cells
- 33. Applications • Poloxamers are used as emulsifying, solubilizing or stabilizing agents to maintain the clarity of elixirs and syrups. • E.g. Poloxamer 188 used as and emulsifying agent for fluorocarbons used as artificial blood substitutes and in the preparation of solid-dispersion. • Also used as wetting agents in Ointments, Suppository bases, and Gels and as tablet binders and Coatings.
- 34. • Poloxamers may also be used therapeutically as Wetting agents in Eye-drop Formulations In the treatment of Kidney stones Skin-wound Cleansers • Poloxamer 338 and 407 are used in Solutions for contact lens care. • E.g. Therapeutically, Poloxamer 188 is administered orally as wetting agent and stool lubricant in the treatment of Constipation.
- 35. • In materials science, the poloxamer P123 has recently been used in the synthesis of mesoporous materials. • Used to increase the water solubility of hydrophobic oily substances or otherwise increase then miscibility of two substances with different hydrophobicities, for these reason used in cosmetics and pharmaceuticals. • Poloxamer-188 improves heart functioning in a rodent model of ischemic heart failure.
- 36. Uses of Poloxamer Uses Concentration(%) Fat Emulsifier 0.3 Flavor Solubilizer 0.3 Fluorocarbon Emulsifier 2.5 Gelling Agent 15-50 Spreading Agent 1 Stabilizing Agent 1-5 Suppository Base 4-6 Tablet Coating 10 Tablet Excipient 5-10 Wetting Agent 0.05-5
- 37. References • International Journal of PharmTech Research; Poloxamers; A pharmaceutical excipients with therapeutic behaviors; Hitesh R. Patel, Rakesh P. Patel, M.M. Patel; Vol.1, No.2, pp 299-303, April-June 2009 • Handbook of Pharmaceutical excipients; Raymond Rowe, Paul Sheskey, Marian Quinn; Sixth edition; pp 506-512,517-522