A study on solubilization of poorly soluble drugs by. The solubility of testosterone in aqueous solutions of partially purified polysorbate 20, 40, and 60 was determined by measuring the area under the ultraviolet spectral peaks. Department of biochemical and pharmaceutical technology, faculty of pharmaceutical sciences, university of sao paulo therefore, the utilization of aqueous micellar solutions for drug solubilization can be advantageous for drug delivery purposes, with the possibility of increasing water solubility. A study on solubilization of poorly soluble drugs by cyclodextrins. Micellar solubilization is a powerful alternative for dissolving hydrophobic drugs in aqueous environments. The drug solubilization locus in the micelles was assessed by uv spectrometry. Carlota oliveira rangelyagui 1, adalberto pessoa junior, leoberto costa tavares department of biochemical and pharmaceutical technology fcf, university of sao paulo, sao paulo, brazil.
Surfactants may enhance herbicide photolysis due to micellar solubilization of the herbicide andor photosensitization if the surfactant contains a chromophore, which absorbs in the near uv wavelengths 290 nm. Solubilization of highly lipophilic drugs in mixed micellar systems and its influence upon drug absorption process summary it is well known that lipid containing mixed micelles show many beneficial features as pharmaceutical carrier systems, especially because of their ability to improve drug. Micellar extraction, based on the cloudpoint phenomenon, and micellar ultrafiltration have been succesfilly applied for preconcentration and removal of organic and inorganic. Consequently, the spatial position of a solubilized drug in a micelle will depend on its polarity. The solubilization of divalent acids and bases is similar to their monoprotic counterpart. Micellar solubilization of poorly watersoluble drugs. Physical chemistry3 classical thermodynamics, nonequilibrium thermodynamics, surface chemistry, fast kinetics module.
Sodium lauryl sulfate sls is one of the common solubilizing agents in pharmaceutical sciences. Techniques of solubilization of drugs 1981 edition. Antonett madriaga, antonina kuzmis, amrita banerjee, alan tang, kevin tao, neil shah, petr kral. This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions. They require enhancement in solubility and dissolution. It is the incorporation of the compound referred to as solubilisate or substrate within micellar l 1 phase or reverse micellar l 2 phase system. Micellar solubilization of poorly watersoluble drugs department of. Techniques to improve the solubility of poorly soluble drugs jinal n. Specifically, the location, orientation and amount of the drug molecules in micelle systems are the focuses of the work.
Included is a discussion of the role of micellar solubilization in catalytic processes. The effect of alkyl sulfates, polysorbates, ethoxylated alcohols, ethoxylated alkyl esters, and alkyl trimethyl ammonium bromides tabs on the solubility of different drugs has been investigated by a number of authors 819. Enhancing solubility and dissolution rate of poorly watersoluble drugs 2. This indicates that carbamazepine is solubilized primarily in the hydrophobic micellar core. Solubilization, micellar catalysis, and microemulsions. Micellar solubilization of some poorly soluble antidiabetic. In order to prepare a liquid dosage formulation of these drugs, a solubilization technique is usually applied. Received 17 november 2004, revised 2 february 2005, accepted 4 march 2005, published 8 july 2005. Micellar solubilization of drugs request pdf researchgate.
Maheswari pd, rambhau d, narasu ml 20 micellar solubilization in the formulation development of poorly soluble naproxen. The solubility is defined as a maximum quantity of solute that can dissolve in a certain quantity of solvent or quantity of solution at a specified temperature 2. Briding the gap between micelles and classical emulsions, the formation and some characteristics of microemulsions is briefly discussed. Bioavailability enhancement of poorly water soluble drugs. Hydrotropy is suggested to be superior to other solubilization method, such as miscibility. These micellar structures can be loaded with hydrophobic drugs during their assembly and can be used to release the drugs on application of a. Besides being used as biomembrane model systems, micelles can be used to solubilize poorly soluble drugs, thus increasing their bioavailability. Besides the solubilization of a drug by physical encap sulation, polymeric micelles can be loaded with hydro phobic molecules that are conjugated or complexed with the polymeric backbone 63. Micellar system can solubilize poorly soluble drugs increasing their. Most of the drugs being poorly water soluble can be easily incorporated into the core of polymeric micelles to overcome solubility problems. Hydrotropic polymer micelles as versatile vehicles for delivery of.
At concentrations above the critical micelle concentration cmc, micelles are formed and they are able to increase the apparent aqueous solubility of poorly soluble drugs. The main objective of this work was to make a systematic study on solubilization of two organic dyes quinizarin with anthraquinone structure and sudan i with azo structure in surfactant micellar solution. Almost more than 90% drugs are orally administered. Chemical structures of a progesterone and b androstane.
Ncyclohexylsulfate salts of several drugs have improved taste and enhanced solubility properties. Journal of drug delivery science and technology 43 2018 44e49 45. The dependence of cocrystal solubilization on surfactant concentration is characterized by nonlinear behavior and an intersection of the solubility curves of cocrystal rha and constituent r solid phases at the csc, critical stabilization concentration. Solubility enhancement usually results in better oral bioavailability of the hydrophobic drugs. Micellar solubilization the use of surfactants to improve the dissolution performance of poorly soluble drug products is probably the basic, primary, and the oldest method. Absorption spectroscopy, conductivity, and surface tension measurements were carried out at 298 k to study the solubilization of poorly soluble drugs sulfamethoxazole smx and trimethoprim tmp in aerosol. In fact, it was observed that for alkyl sodium sulfates and alkyl trimethylammonium bromides, the solubilization of b arteether increases with the increase in the alkyl chain length, due to the larger micellar size 29. Effect of micellar solubilization on cocrystal solubility and.
Equilibrium solubility of two hydrophobic drugs and one. Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications. Advantages of salt it can be effectively applied for the solubilization of weak acids and. Henrys law was also explored for the nalkylbenzenes and 2. Rangelyagui, adalberto pessoajr, and leoberto costa tavares department of biochemical and pharmaceutical technology fcf, university of sao paulo, sao paulo, brazil received 17 november 2004, revised 2 february 2005, accepted 4 march 2005, published 8 july 2005. Micellar solubilization an overview sciencedirect topics. The micellar solubilization of drugs by surfactants is an extensively studied topic 619. The micellar core produces a hydrophobic domain that can be used for solubilization of hydrophobic moieties.
The aim of this study was to improve the dissolution rate of naproxen using micellar solubilization technology. Solubilization of drugs using sodium lauryl sulfate. Khosa department of pharmaceutics, school of pharmacy, bharat institute of technology, partapur, meerut u. Micellar medium as solubilization technique is an influential approach for solubilization of drugs with high hydrophobicity.
Abstract in the present research work, micellar solubilization technology has been employed for the formulation development of poorly soluble naproxen and evaluation was done basing upon the dissolution study. Polymerbased drugs and drug delivery systems emerged from the laboratory bench in the 90s as a promising therapeutic strategy for 19 the treatment of certain devastating human disease5, 6 a number of s. Depending upon the drug hydrophobicity, it can be solubilized in the inner core of the micelle, on the surface of the micelle or at an intermediate location in the palisade layer. Mixed hydrotropy mixed hydrotropic solubilization technique is the phenomenon to increase the solubility of poorly watersoluble drugs in the blends of hydrotropic agents, which may give miraculous synergistic enhancement effect on solubility of poorly water soluble drugs. Pdf micellar solubilization is a powerful alternative for dissolving hydrophobic drugs in aqueous environments. Most of drugs are weakly acidic and weakly basic with poor aqueous solubility. Therefore, one can expect that the solubilization of drugs in the core will increase with increase in asymmetry, whereas the solubilization of drugs in the outer region will decrease 17. Rangelyagui, helen wei ling hsu, adalberto pessoajr, leoberto costa tavares department of biochemical and pharmaceutical technology, faculty of pharmaceutical sciences, university of sao paulo. A solubilization is an emulsion or colloidal dispersion distinguished by the size of the molecule. Apr 20, 2010 micellar solubilization of cocrystals is explained by the distribution of cocrystal components in micellar and aqueous pseudophases. Micellar solubilization solubilization is the process of incorporating the solubilizate the component that undergoes solublization into or onto micelles. Pdf micellar solubilization of poorly watersoluble drugs. A brief description of the role of solubilization on digestion and nutrition is provided for illustrative purposes. Mar 05, 2008 micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs 1214.
The effect was related with the difference in polarity of the drugs studied. In addition to improving solubility and bioavailability of drugs, the use of micelles as drug carriers also presents other advantages such as. Solubilization of poorly soluble drugs is one of the most important physicochemical properties for drug development since more than onethird of drugs are poorly water soluble or water insoluble. Solubilization and micellar and phase transfer catalysis. Solubilization of therapeutic agents in micellar nanomedicines lela vukovic.
Despite extensive studies on polymer micelles, the drug loading, i. Micellar solubilization in the formulation development of. Micellar solubilization of ibuprofen influence of surfactant head groups on the extent of solubilization. Examination of the solubilization of drugs by bile salt. Solubilization techniques authorstream presentation. The micellar structures generated using surfactant molecules have been used in delivering poorly soluble or hydrophobic drugs. Jun 24, 2016 solubilization does not always improve the taste. Hence various techniques are used for the improvement of the solubility of poorly watersoluble drugs include micronization, chemical modification, ph adjustment, solid dispersion, complexation, cosolvency, micellar solubilization, hydrotropy etc. The aim of the present work was to study the mechanism of micellar solubilization of the two model drugs by the commercial surfactant formulation, benzalkonium chloride, so as to shed light on the drugsurfactant interaction in aqueous solution. Some of the basic concepts of micellar catalysis are described and some rules of thumb for predicting the effectiveness of a particular class of surfactant in a given reaction system provided. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. Hydrotropy is suggested to be superior to other solubilization method, such as miscibility, micellar solubilization, cosolvency and salting in, because the solvent character is independent of ph, has high selectivity and does not require emulsification2.
Surfactants reduce surface tension and improve the dissolution of lipophilic drugs in aqueous medium. Department of chemistry, university of illinois at chicago, chicago, illinois 60607, united states department of biopharmaceutical sciences, university. Three series of model drugs, steroids, benzodiazepines and parabens, in three surfactant systems with anionic, cationic and neutral hydrophilic headgroups were studied. In the current work, the effects of tween 80 as a nonionic surfactant on the solubilities of lamotrigine in binary mixts. In this work, we provide an insight into this subject. Solubilization of drugs by cationic surfactants micelles. Five model drugs used in this study are probucol, paclitaxel, progesterone, nifedipine and griseofulvin. Modasiya 1 1, apmc college of pharmaceutical education and research, himatnagar, gujarat india 2, naratha mandal college of pharmacy, belgaum, karnataka. The current study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant. Solubilization of poorly water soluble drug using mixed. Concentrated aqueous hydrotropic solutions of sodium benzoate, sodium salicylate, urea, nicotinamide, sodium citrate and sodium acetate have been observed to enhance the aqueous solubilities of many poorly watersoluble drugs. Pdf micellar solubilization of ibuprofen influence of.
Solubilization of highly lipophilic drugs in mixed micellar. Temperaturedependent solubilization of the hydrophobic. Enhancing permeability of poorly permeable drugs 1. Cloud point temperature of the nonionic surfactants has been used as the basis for the solubility study because there. Hydrotropic polymer micelles as versatile vehicles for delivery of poorly watersoluble drugs ji young kima, sungwon kima, rodolfo pinala, kinam parka,b. Hydrotropy is suggested to be superior to other solubilization method, such as miscibility, micellar solubilization, cosolvency and salting in, because the solvent character is independent of ph, has high selectivity and does not require emulsification 2. Solubilization phenomena are described and related to the chemical structures of the surfactant and additive and other solution characteristics. The binding constants of smx and tmp to aot micelles were determined by applying the benesihildebrand equation. Most commonly used excipients to improve the solubility of a non polar drug in aqueous media are buffers, hydrotropes, surfactants, cosolvents. Techniques to improve the solubility of poorly soluble drugs. Solubilization of insoluble drugs has been extensively studied to. It only requires mixing the drug with the hydrotrope in water. Vinarov z1, katev v1, radeva d1, tcholakova s1, denkov nd1. As free hydrotropes, dena showed considerably greater solubilizing capacity for paclitaxel, whereas dmba showed better ability to solubilize a wide diversity of chemical structures 14.
However upon the ionization of second functional group. Solubilization of organic dyes in surfactant micelles. Interactions and solubilization of poorly soluble drugs in. We employed headspace gas chromatography to measure watertosodium dodecyl sulfate sds micellar partition coefficients for homologous series of nalkylbenzenes, 1nitroalkanes, 1alkanols, and 2ketones. Solubilization of therapeutic agents in micellar nanomedicines. Micellar solubilization of some poorly soluble antidiabetic drugs. Micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs 12 14. Enhancement of solubilization and bioavailability of. Solublization may occur in a system consisting of a solvent, an association colloid a colloid that forms micelles, and at least one other solubilizate. Rangelyagui, helen wei ling hsu, adalberto pessoajr, leoberto costa tavares department of biochemical and pharmaceutical technology, faculty of. Micellar solubilization of ibuprofen influence of surfactant head groups on the extent of solubilization carlota o. Solubilisation is the process of preparation of thermodynamically stable isotropic solution of a substance normally insoluble or sparingly soluble in a given solvent by incorporation of an additional amphiphilic components 26. In case of drug con jugates, there should be a cleavage hydrolysis of the covalent bond between drug and polymer. Surfactants have been used for micellar solubilization of hydrophobic drugs.