WELCOME: WELCOME MICELLE AND CRITICAL MICELLE CONCENTRATION: MICELLE AND CRITICAL MICELLE CONCENTRATION Presented by- Patil Ashish A. Under the guidence of- Dr. Dias R. J. S. C. O. P. Satara. CONTENT: CONTENT Objective. Introduction. Micelle & process of micellization. Role of water in micelle formation. Micelle shape. Manifestation of micelle formation. Structure of micelle. Thermodynamics of micellization. Factors affecting CMC and micelle size. Applications. Conclusion. References. OBJECTIVE: OBJECTIVE To study in detail the concept of micelle & process of micellization. To study the thermodynamics & manifestation of micellization process. Exploring the concept of micelle as a tool in drug delivery system. INTRODUCTION: INTRODUCTION Surfactants-: Surfactants are usually organic compounds that are amphiphilic , meaning they contain both hydrophobic groups (their tails) and hydrophilic groups (their heads). Classification of surfactants. Micelle -: A colloidal aggregate, in a simple geometric form, of a specific number of amphipathic molecules which forms at a well-defined concentration, called the critical micelle concentration. Critical Micelle Concentration-: Critical Micelle Concentration is the concentration at which the surface becomes completely loaded with surfactant and any further additions must arrange as micelles. MICELLE AND PROCESS OF MICELLIZATION: MICELLE AND PROCESS OF MICELLIZATION C lassification of colloidal system. 1) Lyophilic colloid. 2) Lyophobic colloid. 3)Association colloid / micelle MICELLIZATION: MICELLIZATION Behavior of surfactant at different concentration. Reason for micellization . * Attainment of state minimum free energy. * To remove hydrophobic group from aqueous solution ROLE OF WATER IN MICELLE FORMATION : ROLE OF WATER IN MICELLE FORMATION “ Flickering cluster” concept. water exist in two type of arrangement a) Structured water/ Ice like region. b) Water molecule alone. How amphiphile behave in water ? Effect of urea on micelle formation. MICELLE SHAPE: MICELLE SHAPE Type a) spherical b) prolate c) oblate d) disk e) inverted MICELLE SHAPE AS PER TYPE OF SURFACTANT: MICELLE SHAPE AS PER TYPE OF SURFACTANT General Surfactant Type Expected Aggregate Structure Simple surfactants with single chains and relatively large head groups Spherical or ellipsoidal micelles Simple surfactants with relatively small head groups, or ionic surfactants in the presence of large amounts of electrolyte Relatively large cylindrical or rod-shaped micelles Double-chain surfactants with large head groups and flexible chains Vesicles and flexible bilayer structures Double-chain surfactants with small head groups or rigid, immobile chains Planar extended bilayer structures Double-chain surfactants with small head groups, very large, bulky hydrophobic groups Reversed or inverted micelles MANIFESTATIONS OF MICELLE FORMATIONS: MANIFESTATIONS OF MICELLE FORMATIONS Conductivity. Turbidity. Surface tension . STRUCTURE OF MICELLE: STRUCTURE OF MICELLE Type 1) ionic micelle 2) non ionic micelle THERMODYNAMICS OF MICELLIZATION: THERMODYNAMICS OF MICELLIZATION Phase Separation Model Simplest approach treats micelles as a single phase. Mass Action Model Association dissociation equilibrium between free surfactant & micelle phase. PHASE SEPARATION MODEL: PHASE SEPARATION MODEL For non ionic surfactant Δ G 0 M = RT ln [ X cmc ] Δ G 0 M = 2.303 RT [ log cmc - logW ] where, Δ G 0 M -: standard free energy change W -: mole/dm 3 of water PHASE SEPARATION MODEL: PHASE SEPARATION MODEL For ionic surfactant in case of ionic surfactant (1- α ) Δ G 0 M = (2- α ) RT ln [ X cmc ] Δ G 0 M = (2- α )2.303RT [ log cmc - logW ] MASS ACTION MODEL: MASS ACTION MODEL For ionic micelle the ionic micelle, M ++ is consider to be formed by the association of n surfactant ions, D + & (n-p) counter ion X -. nD + + (n-p)X - -> M P+ then std. free energy of micellization per mole of monomeric surfactant is Δ G 0 M = (2- p/n ) 2.303 RT logX cmc Enthalpy and Entropy of Micellization: Enthalpy and Entropy of Micellization The enthalpy of micellization can be calculated from the variation of c.m.c . with temperature. - Δ H 0 = RT 2 ( dln [ X cmc ]/ dT ) The entropy of micellization can be calculated from the relationship between Δ G 0 M and Δ H 0 i.e., Δ G 0 M = Δ H 0 – T Δ S 0 Factors affecting CMC and micelle size: Factors affecting CMC and micelle size 1) Effect of hydrophobic group. -if hydrophobic group is aromatic, micelle does not formed. -length of hydrocarbon chain is directly proportional to micelle size & inversely proportional to CMC. We express this in mathematical term, Log [CMC] = A – Bm where, A & B are homologous series constant. m is the no. of carbon atom in chain. Slide 19: E ffect of hydrophobic group on micelle size &CMC DRUG R1 R2 R3 CMC mole/ kg Micellr aggregation no. DIPHENHYDRAMINE H H H 0.132 3 ORPHENADRINE H CH3 H 0.096 7 BRMODYPHENHYDRAMINE Br H H 0.053 11 CHLORPHENOXAMINE Cl H CH3 0.045 13 Slide 20: 2) EFFECT OF HYDROPHILIC GROUP M icelle size is depend on charge present on head of the ionic micelle. Non ionic micelle is having very low CMC and higher aggregation number. Slide 21: 3) EFFECT OF THE COUNTRION In case of cationic surfactant as the counter ion is charged in series , Cl - , Br - , I - , micelle size is an increase in order for Cl - < Br - < I - . In case of anionic surfactant as the counter ion is charged in series ,Na + , K + , Cs + , micelle size is an increase in order for Na + < K + <Cs + . More weakly hydrated a counter ion larger the micelle formed. 4) EFFECT OF ADDITION OF ELECTROLYTE: 4) EFFECT OF ADDITION OF ELECTROLYTE Addition of electrolyte decreases the CMC &increases the micelles size. Following are the effect of NaCl addition on micelle size of Dodesyl trimethyl ammonium bromide. NaCl concentration in mole/dm3 Critical micelle concentration in mole/dm3 Aggregaton number 0 0.146 61 0.1 0.00428 74 0.502 0.00171 90 Slide 23: What is cloud point ? At temperature up to the cloud point an increase in micelle size &a corresponding decrease in CMC is noted for many non ionic surfactant. 5) EFFECT OF TEMPERATURE APPLICATIONS: APPLICATIONS Micelle increases bioavailability of poorly soluble drugs. Polymeric micelle is used to target the tumor site by passive as well as active mechanism. Micelle is used in ophthalmic drug delivery system, that effectively delivers the drug to posterior tissue of eyeball. Micelle is used to encapsulate the antibiotic & anticancer drugs. Micelle products-: : Micelle products-: 1) Docetaxel Injection Concentrate ( Taxotere ®, Aventis) 2) Amprenavir oral solution and capsules ( Agenerase ®, GSK) 3) NK911 ( Miceller Doxorubicini hydrochloride) 4) NK105 ( Miceller Paclitaxel ) CONCLUSION : CONCLUSION Micelle is very good solution on weakly soluble drug which enhances their bioavailability. Recent work on cancer therapy shows that micelle is a good carrier for drug used in cancer therapy. Micelle doesn’t harm to other system of our body and also having patient compliances. By considering all things regarding micelle, micelle is beneficial in drug delivery system and more research is expected in future so that this wonderful phenomena can be used in new drug delivery system. REFERENCES : REFERENCES Dr. Tadros F. T., “Applied surfactant, principles & applications” , die deutsche bibliothek publication, p. no. 19-46. Myers D., ”surfactant science & technology”, 3 rd edition, john wiley & sons publication, new jersey, p. no.107-157. Holmberg K., Jonsson B., Kronberg B., Lindman B., “ surfactant &polymer in aqueous solution”, John wiley & sons publication, p. no. 31-66. Slide 28: Bramhankar D. M., Jaiswal S. B., “ Biopharmaceutics & Pharmacokinetics”, 1st edition, Vallabh prakashan , p. no.44. Attwood D., Florence A. T., “Surfactant system”, p. no.388-463. Go-Gang Chang, Ter -Mei Haung , Review paper, “Reverse micelle as life-mimicking systems”. Yohinobu Neno , Naohide Hirashima , Yoshikazu Inon , Tadahide Furuno , “Characterization of Biosurfactant containing Liposome & their efficiency for gene transfection ”, Biol. Pharm. Bull, Vol. 30. Alfrade Martin, James Warbrick , Arthur Cammarata , "Physical pharmacy", 3rd edition, published by K. M. Verghese company, p. no.453-458, 465-467.