Surfactants are known to play a vital role in many processes of interest in both fundamental and applied science. Cloud point and dye solubilization studies of amphiphilic. 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. The c value is defined as the number of moles of the solute drug that can be solubilized by one mol of micellar surfactant, and. The purpose of this work was to investigate the solubilitypermeability interplay when using hydrotropic drug solubilization. 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. Micellar solubilization of some poorly soluble antidiabetic. Selfassociation and cyclodextrin solubilization of drugs. Natco research centre, natco pharma limited, sanathnagar, hyderabad 500 018, andhra pradesh, india 2.
Pdf micellar solubilization of poorly watersoluble drugs. Lough skip to main content accessibility help we use cookies to distinguish you from other users and to provide you with a better experience on our websites. Micellar solubilization of fatty acids in aqueous media containing bile salts and phospholipids volume 35 issue 1 a. Specifically, the location, orientation and amount of the drug molecules in micelle systems are the focuses of the work. Micellar solubilization of fatty acids in aqueous media. Figure 7a shows the solubility change of poorly soluble model drugs smx and tmp as a function of sds concentration. A study on solubilization of poorly soluble drugs by cyclodextrins. 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. Micellar solubilization of clofazimine analogues in. Received 17 november 2004, revised 2 february 2005, accepted 4 march 2005, published 8 july 2005. 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. It covers the techniques and solubilization process of these insoluble drugs. Purpose micellar solubilization is a powerful alternative for dissolving hydrophobic drugs in aqueous environments. Micellar solubilization of clofazimine analogues in surfactants solution.
The use of phosphate solubilizing bacteria as inoculants increases the p. Micellar solubilization an overview sciencedirect topics. Initially, a description of surfactants and aqueous micellar systems is presented. Consequently, the spatial position of a solubilized drug in a micelle will depend on its polarity. Maheswari pd, rambhau d, narasu ml 20 micellar solubilization in the formulation development of poorly soluble naproxen. 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 this work, we provide an insight into this subject. The underlying premise is that with better information regarding the inherent biological complexity, efforts to predict the oral bioavailability of drug will be enhanced. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. Temperaturedependent solubilization of the hydrophobic. Three series of model drugs, steroids, benzodiazepines and parabens, in three surfactant systems with anionic, cationic and neutral hydrophilic headgroups were studied. Engineering cocrystal solubility and stability via ionization.
Micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs 12 14. 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. Cremophor is polyoxylethylated castor oil in which fatty acid esters of glycerol represent the hydrophobic portion, and the polyethylene glycol represent the hydrophilic. The solubilization of the unsaturated lipids p90g and os in the studied micellar systems was distinctly higher than it was for their. In order to prepare a liquid dosage formulation of these drugs, a solubilization technique is usually applied. Few studies have been reported on the role of additives in ionic drug micellar behavior.
Pdf selfassociation and cyclodextrin solubilization of. Micellar solubilization of ibuprofen influence of surfactant. The solubilization of divalent acids and bases is similar to their monoprotic counterpart. Equilibrium solubility of two hydrophobic drugs and one. 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. Micelle formation is a natural property of bile acids, which are secreted into the duodenum under physiological conditions and which play an important role in fat absorption by the intestine. Solublization may occur in a system consisting of a solvent, an association colloid a colloid that forms micelles, and at least one other solubilizate. 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.
The binding constants of smx and tmp to aot micelles were determined by applying the benesihildebrand equation. Solubilization of poorly soluble drugs is a frequently encountered challenge in screening studies of new chemical entities as well as in formulation design and development 1,2. These micellar structures can be loaded with hydrophobic drugs during their assembly and can be used to release the drugs on application of a. In addition to improving solubility and bioavailability of drugs, the use of micelles as drug carriers also presents other advantages such as. The underlying premise is that with better information regarding the inherent. Recommended citation feng, shaoxin, studies on drug solubilization mechanism in simple micelle systems 2009. Micellar solubilization in the formulation development of. Nonionic microemulsions as solubilizers of hydrophobic. Apr 20, 2010 micellar solubilization of cocrystals is explained by the distribution of cocrystal components in micellar and aqueous pseudophases. It only requires mixing the drug with the hydrotrope in water. Enhancement of solubilization and bioavailability of. Solubilization of therapeutic agents in micellar nanomedicines.
Micellar solubilization of clofazimine analogues in surfactants solution what is it about. The c value is defined as the number of moles of the solute drug that can be solubilized by one mol of micellar surfactant, and characterizes the ability of the surfactant to solubilize the drug. Effect of micellar solubilization on cocrystal solubility and. Micellar solubilization of smx and tmp by sds and cds. In case of drug con jugates, there should be a cleavage hydrolysis of the covalent bond between drug. Examination of the solubilization of drugs by bile salt. 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. Pdf micellar solubilization is a powerful alternative for dissolving hydrophobic drugs in aqueous environments. Estimation of cocrystal solubilization from drug solubilization. The solubilization of a number of steroids was determined in bile salt simple micelles and a bile saltphospholipid micellar system to provide a better basis to predict the extent of drug solubilization in vivo. The aim of this study was to improve the dissolution rate of naproxen using micellar solubilization technology. Importantly, 1 m arginine was more effective in augmenting the solubilization effect of lauroyllglutamate than that of sds.
Surfactants have been used for micellar solubilization of hydrophobic drugs. Micellar solubilization of some poorly soluble antidiabetic drugs. Hence various techniques are used for the improvement of the solubility of poorly watersoluble drugs include micronization, chemical modification, ph adjustment, solid dispersion, complexation, co. Micellar solubilization of clofazimine analogues in aqueous solutions of ionic and nonionic. Drug development and industrial pharmacy 2018, 44 4, 677686. However upon the ionization of second functional group. The drug paclitaxel is highly lipophilic in nature and insoluble in water. Cloud point temperature of the nonionic surfactants has been used as the basis for the solubility study because there is better entrapment of the drug into the surfactant micelle at. This work describes the solubility of a number of riminophenazines in aqueous surfactants solutions in order to increase the solubility of these sprigly soluble antimicrobial comounds. The effect of alkyl sulfates, polysorbates, ethoxylated alcohols, ethoxylated alkyl esters, and alkyl trimethyl ammonium bromides. Thus, the ph adjustment may be the most simple, economic and effective way of increasing the aq. Micellar solubilization solubilization is the process of incorporating the solubilizate the component that undergoes solublization into or onto micelles.
For ionizable drugs, the aqueous solubility is strongly influenced by the ph of the solvent. Besides this micellar solubilization can improve permeability of poorly soluble drugs via gastrointestinal tract membranes thereby enhancing oral bioavailability. 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. Cancelpaclitaxel ptx solubility and to study the chemical structures nec essary for. Enhancement of solubilization and bioavailability of poorly. The micellar solubilization of drugs by surfactants is an extensively studied topic 619. Mar 05, 2008 micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs 1214. 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. 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. Micellar drug formulations are thus an extension of a normal physiological process. Solubilization techniques authorstream presentation. Usually, the solubilization of a molecule by a surfactant can be evaluated based on two descriptors. Fifty millimolar lauroyllglutamate was more effective than 50 mm sds against shortchain alkyl gallates, which may reflect a different micellar form between these two detergents. 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.
Therefore, the utilization of aqueous micellar solutions for drug solubilization can be advantageous for drug delivery purposes, with the possibility of increasing water solubility of poorly soluble drugs, improving bioavailability, reducing toxicity and other side effects, enhancing permeability across the physiological barriers, and. This study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant solutions. Micellar solubilization is also a powerful alternative for dissolving hydrophobic drugs in aqueous environments. Solubilization of drugs by physiological mixtures of bile. Micellar solubilization is a widely used alternative for the dissolution of poorly soluble drugs 1214. Introduction poor water solubility of drugs is the most important hurdle in the pharmaceutical industry and research. There are very limited reports in the literature on the e. Carlota oliveira rangelyagui 1, adalberto pessoa junior, 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. Surfactants reduce surface tension and improve the dissolution of lipophilic drugs in aqueous medium.
The micellar structures generated using surfactant molecules have been used in delivering poorly soluble or hydrophobic drugs. 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. The dye solubilization technique has been widely used to study the micellar behavior of surfactants mitra and dungan, 2000. Micellar solubilization of poorly watersoluble drugs. An important property of micelles with particular significance in pharmacy is their ability to increase the solubility of poorly soluble drugs in water, thus increasing. Interactions and solubilization of poorly soluble drugs in.
Cloud point temperature of the nonionic surfactants has been used as the basis for the solubility study because there. The objectives of this work are to 1 understand the effect of ionization on cocrystal solubility, 2 investigate the role of micellar solubilization on cocrystal solubility and stability, 3 develop mathematical models to describe cocrystal solubility and stability via ionization and micellar solubilization equilibria, and 4 understand. Frontiers hydrotropic solubilization of lipophilic drugs. Drug solubilization effect of lauroyllglutamate the. Besides being used as biomembrane model systems, micelles can be used to solubilize poorly soluble drugs, thus increasing their bioavailability. Solubilization by ph for a drug to be formulated in a liquid dosage form is generally required to be. Solubilization of highly lipophilic drugs in mixed. Micellar and nonmicellar patterns of self association of hydrophobic solutes of different molecular structuresmonomer fraction, availability and misuse of micellar hypothesis. Excess solid drug was dispersed in taurodeoxycholate or mixed micelle solutions prepared with fixed mole ratios of taurocholate, taurodeoxycholate. 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. Micellar solubilization of clofazimine analogues in aqueous. Physical chemistry3 classical thermodynamics, nonequilibrium thermodynamics, surface chemistry, fast kinetics module. The current study aims to clarify the role of surfactant and drug molecular structures on drug solubility in micellar surfactant.
While it can certainly increase the apparent solubility of a lipophilic drug, the effect of hydrotropy on the drugs permeation through the intestinal membrane has not been studied. As seen in figure 7a, the plots of drug solubility against surfactant concentrations can be divided into two straight lines. Bioavailability, solubilization, chemical modifications introduction solubilization of poorly soluble drugs is a frequently encountered challenge in screening studies of new chemical entities as well as in formulation design and development 1,2. Results initially, a description of surfactants and aqueous micellar systems is presented. An understanding of the selfaggregation mechanism of amphiphilic drugs at the molecular level and their solubilization by the surfactants is crucial in the rational design of more effective drug delivery systems schreier et al. A solubilization is an emulsion or colloidal dispersion distinguished by the size of the molecule. Nov 29, 2012 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. For this purpose, we have studied the solubilization of the hydrophobic drug lam in.
Engineering cocrystal solubility, stability, and phmax by. Interactions and solubilization of poorly soluble drugs in aerosola. Examination of the solubilization of drugs by bile salt micelles examination of the solubilization of drugs by bile salt micelles wiedmann, timothy scott. Carlota oliveira rangelyagui 1, adalberto pessoa junior, leoberto costa tavares department of biochemical and pharmaceutical technology fcf, university of sao paulo, sao paulo, brazil. Notably, the micellar solubilization was known earlier to formulation scientists and work well in small molecular drugs, while microemulsionliposomes are often applied to the encapsulation of larger drug molecules 1,37,9,10. The obtained results illustrate that atomistic simulations can reveal drug solubilization. Micellar solubilization of drugs request pdf researchgate. Micellar solubilization in the formulation development of poorly soluble. A study on solubilization of poorly soluble drugs by. Engineering cocrystal solubility, stability, and phmax by micellar solubilization 90 introduction 90 theoretical 92 cocrystal solubilization and thermodynamic stabilization in micellar solutions 93 estimation of cocrystal solubilization from drug solubilization 97. Most of drugs weakly acidic and weakly basic with poor aqueous solubility.
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