Tolnaftate Drug Profile:

Tolnaftate Drug ProfileTrade designation TinactinSynonym Tolnaftato, TolnaftatumStructure human body Structure of Tolnaftate chemic Name0-2- naphthyl methyl (3- methyl phenyl thiocarbamate)DescriptionTolnaftate is a synthetic thiocarbamate utilise as an anti- fungal operator that whitethorn be sold without medical prescription in most jurisdictions. It may come as a cream, pulverization, spray, or naiant aerosol, and is utilize to contend fungal conditions such as jock itch, athletes foot and ringworm. It is sold under several brand name c aloneing in including Tinactin, odor Eaters, Absorbine, Aftate, tinkle (85) .Molecular Weight 307.41 g/molMechanism of ActionTolnaftate is a topical antimycotic agent. Though its particular mechanism unknown, it is believed to interdict Ergo sterol biosynthesis by inhibiting squalene epoxidase (86) . It has withal been reported to reach the hyphae and to stunt mycelia growth in susceptible organisms (87) .Melting Point 110- 111.50C ( 230- 2330F)Pharmacological ActionTolnaftate, a pharmacologically inert new fungicide for topical treatment of superficial mycoses, has been reported to be highly powerful in skin infections cause by common pathogenic fungi as well as universe non- irritating and non- sensitizing. It is a antifungal invitro. During clinical investigation, studies showed no changes in the blood and urine of patients given tolnaftate topically, suggesting that the do doses is not toxic to the kidney or the hematopoietic system. Distorts hyphae and inhibits mycelia growth in susceptible fungi. The anti- dermatophyte agent to tolnaftate was compargond with the allylamine anti-fungal compounds naftifine and terbinafine. Tolnaftate was shown to inhibit sterol biosynthesis at the aim squalene epoxidation and squalene was shown to accumulate in dermatophytes grown in its presence. Biochemical studies in self-coloured and broken cells supported this certainty and showed that the compound was active aga inst squalene epoxidation in broken candida albicans cells, but was mwch less unattackable against whole cells. These results suggested in that location was a barrier to penetration in these yeasts (88) .Side EffectsIrritationPruritusContact dermatitisOnset 24- 72 Hours dosageTopical/ cutaneous Superficial dermatophyte infections, pityriasis versicolor.Adult Apply a 1% gel / dissolving agent /powder /cream bid for 2-6 calendar weeks repeat if necessary. Continue treatment for 2 weeks after disappearance of all symptoms to prevent recurrence of infection.StorageTopical/Cutaneous Store at 15-300CTOLNAFTATE DRUG PROFILETrade name TinactinSynonym Tolnaftato, TolnaftatumStructureFig Structure of TolnaftateChemical Name0-2- naphthyl methyl (3- methyl phenyl thiocarbamate)DescriptionTolnaftate is a synthetic thiocarbamate used as an anti- fungal agent that may be sold without medical prescription in most jurisdictions. It may come as a cream, powder, spray, or liquid aerosol, and is u sed to treat fungal conditions such as jock itch, athletes foot and ringworm. It is sold under several brand names in including Tinactin, odor Eaters, Absorbine, Aftate, Ting (85) .Molecular Weight 307.41 g/molMechanism of ActionTolnaftate is a topical fungicide. Though its exact mechanism unknown, it is believed to prevent Ergosterol biosynthesis by inhibiting squalene epoxidase (86) . It has also been reported to distort the hyphae and to stunt mycelia growth in susceptible organisms (87) .Melting Point 110- 111.50C (230- 2330F)Pharmacological ActionTolnaftate, a pharmacologically inert new fungicide for topical treatment of superficial mycoses, has been reported to be highly effective in skin infections caused by common pathogenic fungi as well as being non- irritating and non- sensitizing. It is a fungicidal invitro. During clinical investigation, studies showed no changes in the blood and urine of patients given tolnaftate topically, suggesting that the drug is not toxic to the kidney or the hematopoietic system. Distorts hyphae and inhibits mycelia growth in susceptible fungi. The anti- dermatophyte agent to tolnaftate was compargond with the allylamine anti-fungal compounds naftifine and terbinafine. Tolnaftate was shown to inhibit sterol biosynthesis at the level squalene epoxidation and squalene was shown to accumulate in dermatophytes grown in its presence. Biochemical studies in whole and broken cells supported this conclusion and showed that the compound was active against squalene epoxidation in broken candida albicans cells, but was mwch less potent against whole cells. These results suggested there was a barrier to penetration in these yeasts (88) .Side Effects1.Irritation2.Pruritus3.Contact dermatitisOnset 24- 72 HoursDosageTopical/ cutaneous Superficial dermatophyte infections, pityriasis versicolor.Adult Apply a 1% gel / solution /powder /cream bid for 2-6 weeks repeat if necessary. Continue treatment for 2 weeks after disappearance of all sy mptoms to prevent recurrence of infection.StorageTopical/Cutaneous Store at 15-300C3.2.1 LECITHINSynonymsPc kelecin LECITHIN Alcolec-S granulestin L-Lecithin LIPOID(R)E80 Lecithin, NF Phospholutein E322 egg lecithin LSC 5050 LSC 6040 mingled soy phoaphatides ovolecithin Phosal 53 MCT Phospholipon 100 H Prokote LSC soybean lecithin soybean phospholipids Sternpur vegetable lecithin (89) .StructureWhere red choline and inorganic phosphate conference black glycerol green-unsaturated sebaceous acid Blue saturated roly-poly acid.Chemical name1,2-diacyl-sn-glycero-3-phosphatidylcholineMolecular pack789 g/molDescriptionLecithin occurs sportsmanlike yel junior-grade to dark brown, transp bent or translucent, viscous liquid substance, as white to brown powder or granules, or as a light yellow to dark brown lump, having a slight, characteristic odour and taste.Identification (1) Place 1 g of lecithin into a kjeldahl flask, add 5 gm of powdered potassium sulphate and 0.5 gm of cupric sulfate, and 20 ml of sulfuric acid. Tilt the flask at active 45C angle, hot pants gently until the effervesense , and raise the temperature to boiling. After the contents become blue, transpargonnt solution, heat for 1-2 hours, cool and add an friction match volume of water. Take 5 ml of this solution, and add 10 ml of ammonium molybdate solution (1 5), and heat. A yellow precipitate is formed. (2) To 0.5 g of lecithin, add 5 ml of diluted hydrochloric acid(12), heat in a water bath for 2 hours and filter. Use this solution is considered as a test solution. Perform piece chromatography with 10 l of the test solution, using choline chloride solution (1 200) as the mastery solution and a compart psychicization of n-butanol, water, and acetic acid (421) as the developing solvent. A red orange spot is obtained from the control solution is observed. In paper chromatography for the filter paper, use a No. 2 filter paper. immobilize the development when the developing solvent ris es about 25 cm, air-dry, spray with Dragendorffs reagent to develop a colour, and observe in daylight (90) .SolubilityIn fat- dissolvable in cold water and also acetone. Soluble in about 12 parts of absolute alcohol. Soluble in chloroform, petroleum ether, mineral oil and fatty acids. meagrely soluble in benzene. Insoluble in cold vegetable oils and animal oils (91) .ViscosityViscosity of lecithin is instantaneously influenced by heat. Lower temperature equals higher viscosity and vise versa. The influence of temperature on lecithin viscosity is curvilinear, meaning that at low temperatures, a small increase in heat causes a elatively larger decrease in viscosity. For example, a lecithin with a viscosity of 10,000 centipoise at 24 0C, might puzzle a viscosity of 5000 centipoise at 350C. An increase in temperature to 460C might lower the viscosity to 3000 centipoise and further increase to 570C would reduce viscosity to 2250 centipoise. combine oil, such as soybean oil or fish oi l, with the lecithin at a rate of 20 % oil and 80 % lecithin as a similar influence on viscosity as ski lift temperature by 110C. In other words, a standard fluid lecithin with 10,000 centipoise viscosity when mixed with 20 % soybean oil would soak up an approximate viscosity of 5000 centipoise (92)TYPICAL PROPERTIESAcidity/alkalinitypH = 5.58.0 for a 1 % w/w aqueous solutionAsh1.53.0 %, depending upon the grade and viscosityAuto ignition temperature360C niggardliness (bulk)0.341 g/cm3Density (tapped)0.557 g/cm3Density (true)1.326 g/cm3Specific gravity1.26Melting pointBrowns at 190200 C.Chars at 225230 C.Glass transition temperature is 170180 C.Iodine number95-100 for liquid lecithin.82-88 for powdered lecithin.Saponification number196Functional CategoryLecithin is a generic term to designate any group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk. It is naturally composed of phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids. It is often used as an emulsifying agent.Available in variety of forms including granules, soft gels and chewable tablets.ApplicationsLecithins be used in a wide variety of pharmaceutical applications. They argon also used in cosmetics and viands products.Lecithins are mainly used in pharmaceutical products as dispersing, emulsifying, and stabilizing agents, and are included in intramuscular and intravenous injections, parenteral nutrition formulations, and topical products such as creams and ointments. Lecithins are also used in suppository bases to reduce the brittleness of suppositories, and have been investigated for their absorption-enhancing properties in an intranasal insulin formulation.Lecithins are also commonly used as a component of enteral and parenteral nutrition formulations. There is evidence that phosphatidylcholine (a major component of lecithin) is important as a nutritional supplement to fetal and infant development. Furthermo re, choline is a required component of FDA-approved infant formulas. different studies have indicated that lecithin can protect against alcohol cirrhosis of the liver, lower serum cholesterol levels, and improve mental and physical performance. Liposomes in which lecithin is included as a component of the bilayer have been used to encapsulate drug substances their potential as novel delivery systems has been investigated.This application generally requires purified lecithins combined in specific proportions. Therapeutically, lecithin and derivatives have been used as a pulmonary surfactant in the treatment of neonatal respiratory distraint syndrome.mnbStability and entrepot conditionsLecithins decompose at extreme pH. They are also hygroscopic and subject to microbial degradation. When heated, lecithins oxidize, darken, and decompose. Temperatures of 1601808C will cause degradation within 24 hours. Fluid or waxy lecithin grades should be stored at room temperature or above temper atures below 108C may cause separation. All lecithin grades should be stored in well-closed containers protected from light and oxidation. Purified solid lecithins should be stored in tightly closed containers at subfreezing temperaturesIncompatibilitiesIncompatible with esterases owe to hydrolysis.SafetyLecithin is a component of cell membranes and is therefore consumed as a normal part of the diet. Although unreasonable consumption may be harmful, it is highly biocompatible and oral doses of up to 80 g daily have been used therapeutically in the treatment of auction pitchdive dyskinesia.(8) When used in topical formulations,lecithin is generally regarded as a nonirritant and nonsensitizing material.(2) The Cosmetic Ingredients Review Expert Panel (CIR) has reviewed lecithin and issued a tentative report revising the risk-free concentration of the material from 1.95% to 15.0% in rinse-off and leave-in products. They note, however, that there are insufficient data to rule on prod ucts that are likely to be inhaledHandling precautionsLecithins may be irritant to the eyes eye protection and gloves are recommended.Regulatory statusGRAS listed (Generally Recognized as Safe). Accepted for use as a food analog in Europe. Included in the FDA Inactive Ingredients Database (inhalations IM and IV injections otic preparations oral capsules, suspensions and tablets rectal, topical, and vaginal preparations). Included in nonparenteral and parenteral medicines licensed in the UK. Included in the Canadian List of pleasing Non-medicinal Ingredients.3.2.2 SPAN80Nonproprietary NamesSorbitan monooleateSynonymsAblunol S-80 Arlacel 80 Armotan MO Capmul O Crill 4 Crill 50 Dehymuls SMO Drewmulse SMO Drewsorb 80K E494 Glycomul O Hodag SMO Lamesorb SMO Liposorb O Montane 80 Nikkol SO-10 Nissan Nonion OP-80R Norfox Sorbo S-80 Polycon S80 K Proto-sorb SMO Protachem SMO S-Maz 80K Sorbester P17 Sorbirol O sorbitan oleate Sorgen 40 Sorgon S-40- H Span 80 Tego SMO.StructureChemical name C24H44O6(Z)-Sorbitan mono-9-octadecenoateMolecular weight 429 g/molDescriptionSpan80 occur as Yellow viscous liquid with a classifiable odour and taste.SolubilitySorbitan esters are generally soluble or dispersible in oils they are also soluble in most organic solvents. In water, although insoluble, they are generally dispersible.ViscosityTypical viscosity set for span80 1200-2000 mPa.s measured at 20CTypical propertiesHLB value 4.3Density 1.01g/cm3Saponification value 149-160Functional phratryEmulsifying agent, non ionic surfactant, solubilizing agent, wetting, dispersing and suspending agent.ApplicationsA non-ionic surfactant that can be used to form oil-in-water emulsions and in combination with low HLB surfactants can form water-in-oil emulsions. EPA approved oil spill dispersant.Sorbitan monoesters are a series of mixtures of partial esters of sorbitol and its mono- and dianhydrides with fatty acids. Sorbitan diesters are a series of mixtures of partial esters of sorbitol and its monoanhydride with fatty acids.Sorbitan esters are wide used in cosmetics, food products, and pharmaceutical formulations as lipophilic nonionic surfactants. They are mainly used in pharmaceutical formulations as emulsifying agents in the preparation of creams, emulsions, and ointments for topical application. When used alone, sorbitan esters produce stable water-in-oil emulsions and microemulsions but are frequently used in combination with varying proportions of a polysorbate to produce water-in-oil or oil-in-water emulsions or creams of varying consistencies.Sorbitan monolaurate, sorbitan monopalmitate and sorbitan trioleate have also been used at concentrations of 0.010.05% w/v in the preparation of an emulsion for intramuscular administration.Stability and storage conditionsGradual soap formation occurs with strong acids or bases. Sorbitan esters are stable in weak acids or bases. Sorbitan esters should be stored in a well-closed container in a cool, dry place.SafetySo rbitan esters are widely used in cosmetics, food products, and oral and topical pharmaceutical formulations and are generally regarded as nontoxic and nonirritant materials. However, there have been occasional reports of hypersensitive skin reactions following the topical application of products containing sorbitan esters. When heated to decomposition, the sorbitan esters emit cutting smoke and irritating fumes. The WHO has set an estimated pleasing daily intake of sorbitan monopalmitate, monostearate and tristearate and of sorbitan monolaurate and monooleate at up to 25 mg/kg body-weight calculated as total sorbitan esters.Regulatory statusCertain sorbitan esters are accepted as food additives in the UK. Sorbitan esters are included in the FDA Inactive Ingredients Guide (inhalations IM injections ophthalmic, oral, topical and vaginal preparations). Sorbitan esters are used in nonparenteral medicines licensed in the UK. Sorbitan esters are included in the Canadian List of Acceptab le Non-medicinal Ingredients.3.2.3 TWEEN 80Non-proprietary namesPolysorbate 80SynonymsAtlas E Armotan PMO 20 Capmul POE-O Cremophor PS 80 Crillet 4 Crillet 50 Drewmulse POE-SMO Drewpone 80K Durfax 80 Durfax 80K E433 Emrite 6120 Emulgin SMOGlycospere O-20 Hodag PSMO-20 Liposorb O-20 Liposorb O-20K Montanox 80 Polyoxy ethylene 20 oleate Protasorb o- 20 Ritabate 80(Z)-sorbitan mono -9-octadecenoate poly(oxy1,2- ethanediyl) derivatives Tego SMO 80 Tego SMO 80V Tween 80.Structural formulaChemical namePolyoxyethylene 20 sorbitan monooleateEmpirical formulaC64H124026Molecular weightM.W 1310Functional categoryIt acts as an Emulsifying agent nonionic surfactant solubilizing agent wetting agent and also dispersing/suspending agentDescriptionIt is colorless to light yellowish viscous liquid.Typical PropertiesHLB value 15Density 1.08 g/ml at 20 cSaponification value 45-55P H 5% aq solution 5.5-7.5Specific gravity (20/20c) 1.065-1.095wet contentMoisture content not more than 3%SolubilitySolubl e in water and also soluble in ethanol. Insoluble in mineral oils.Viscosity (dynamic)The viscosity of tween 80 is 300-500 centi stokes at 25cApplications of tween80 in pharmaceutical formulation or technologyPolyoxyethylene sorbiton fatty acid esters (polysorbates) are a series of partial fatty acid esters of sorbitol and its anhydrides copolymerized with approximately 20, 5 or 4 moles of ethylene oxide per each mole of sorbitol and also sorbitol anhydrides. The resulting product is therefore a mixture of molecules of varying sizes rather than in single uniform compound. Polysorbates containing 20 units of oxy ethylene are hydrophilic nonionic surfactants that are used widely as emulsifying agent in the preparation of stable oil-in-water pharmaceutical emulsions. They may also be used as solubilizing agent for a variety of substances including essential oils and also other oils like oils are soluble vitamins, and teen 80 as a wetting agent in the formulation of oral and parenteral s uspensions. They also have been useful in improving the oral bioavailability of drug molecule that are substrates for P-glycoprotein.Polysorbates are also used in cosmetics and also food products.Stability and storage conditionsPolysorbates are stable to electrolytes and week acids and bases gradual saponification occurs with strong acids and strong bases. This type of oleic acid esters are sensitive to oxidation. Polysorbates are hygroscopic and should be examined necessary for water content before to use and dried if necessary. Prolonged storage of tween 80 along with other polyoxyethylene surfactants can leads to the formation of peroxides. Polysorbates should be stored in a well closed containers, protected from the light, in a cool and dry place.IncompatabilitiesDiscoloration and /or precipitation occur with various substances especially phenols, tannins, tars, tar like materials.The anti microbial activity of paraben preservatives is reduced in the presense of polysorbates.Reg ulatory statusPolysorbate60, 65and 80 are GRAS listed. Polysorbates 20, 40, 60, 65and 80 are accepted as food additives in Europe. Polysorbates 20, 40, 60, 65and 80 are included in the FDA inactive ingredients guide (IM,IV,oral,rectal,topical and vaginal preparations). Polysorbates are included in parenteral and non parenteral medicines licensed in the UK. Polysorbate such as 20, 21, 40, 60, 61, 65, 80, 81, 85 and 120 are included in the Canadian list of acceptable non medicinal ingredient.