Hydrotropic Solubilization. Priyanka Arjaria1, Manoj Goyal2, Suman Jain3. 1Shri Ram College of pharmacy,Banmore,Morena, India, 2IPS College of pharmacy. Purpose. This study examines the mechanism of hydrotropic solubilization using the riboflavin-nicotinamide system. The most commonly proposed mechanism. On the other hand, planarity of the hydrophobic part has been emphasized as an important factor in the mechanism of hydrotropic solubilization. Solute consists.
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Solubility of drug is considered to be one of the crucial parameter to achieve its desired concentration in systemic circulation and better pharmacological response. As most of the drugs available are poorly aqueous soluble, solubility enhancement has become major challenge to the formulators in the product development of many orally administered drugs. Therapeutic response of drug as well bioavailability can be limited by poor aqueous solubility of drugs. Earlier, many techniques have been developed for enhancing solubility of drugs.
Apart from those, hydrotropic solubilization is one of the solubility enhancement techniques applicable to enhance solubility of hydrophobic drugs with the use of hydrotropes like sodium benzoate, urea, piperazine etc.
In the present investigation Lumefantrine, an anti malarial drug was selected as model drug for the reason it has very low water solubility of 0. The key objective of current research work was to enhance aqueous solubility of this drug using hydrotropic solubilization technique. Solubility studies were performed using various concentrations of hydrotropes like sodium citrate, sodium benzoate, etc.
Formulation plays a prominent role and holds several benefits in drug discovery and development.
Therapeutic efficacy of drug preliminarily depends upon the bioavailability of drug which ultimately upon the solubility of drug molecules. Poor aqueous solubility of drugs often causes significant problems in developing formulations showing high bioavailability. Therefore, solubility is one of the important parameter to be considered in the product development in order to achieve desired concentration of drug in systemic circulation which further gives effective pharmacological response.
Formerly, several techniques have been developed to enhance the aqueous solubility of poorly water-soluble drugs such as complexation, cosolvency, emulsions, liposomes, particle size reduction, solid state alteration, solid dispersions, prodrugs, salt formation, polymeric micelles, etc.
Hydrotropic solubilization is one among those techniques wherein addition of large amount of second solute increases aqueous solubility of another solute.
Hydrotropy enhances solubility of drug by many folds with use of hydrotropes like sodium benzoate, sodium citrate, urea, niacinamide etc. Hydrotropic agents are also a type of solubilizers which increase the solubility of poorly water soluble drugs 3. Examples of various hydrotropic agents that are used as excipients in order to increase aqueous solubility of drug are urea, nicotinamide, sodium benzoate, sodium salicylate, sodium acetate, piperazine, nicotinamide, sodium toluate 4 – Here, Lumafantrine was selected as model drug.
Lumefantrine, also known as Benflumetol, is basically a long acting anti-malarial drug which is very effective in treatment of resistant P. It is an erythrocytic schizontocide and acts by inhibiting haeme polymerization in the food vacuole of plasmodia. Hence it is necessary to increase the solubility of drug that may further increase bioavailability and also results in reduction of dose. Here artemether is short acting where as lumefantrine is long acting anti malarial drug.
Keeping this point in view, the present research work is focused to enhance solubility of Lumefantrine using hydrotropic solubilization technique. The effect of hydrotropes like sodium benzoate, sodium citrate, sodium gluconate, ammonium acetate, piperazine, etc. Lumefantrine was kindly gifted from Cipla, Pithampur, India. Sodium gluconate, Piperazine anhydrous and L-ascorbic acid were purchased from Molychem, Mumbai, India.
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Sodium benzoate, Tri-sodium citrate dihydrate were purchased from Rankem, Haryana, India. Urea and Ammonium acetate were purchased from Qualigens, Mumbai, India. All the chemicals and reagents used were of analytical grade.
About 20 mg of drug was accurately weighed and dissolved in ml of methanol R by sonication for hydrotroopic 15 minutes. The solution was solubilixation to cool to room temperature and diluted five times with methanol R. Preparation of Calibration Curve of Lumefantrine in 0. Standard stock solution of Lumefantrine was prepared by dissolving mg of drug in ml of 0.
From the above solution 1, 2, 3, 4, 5 and 6 ml was taken and diluted upto 10ml with 0. Here, diamond is the preferred choice for most applications because of its robustness and durability. Force is applied on to the sample, pushing it onto the diamond surface. Transmittance was measured from hydrptropic number cm -1 to -1 applying Happ-Gensel apodization.
After shaking, the samples were examined for the presence of any undissolved suspended particles and clarity. The results of qualitative solubility of Lumefantrine in various solvents were reported in Table 3.
An excess amount of solute is dissolved in 10 ml of selected solvent till saturated solution was obtained. After 24 hrs equilibrium was attained and the samples were filtered through Whatman filter paper No. The individual samples were analyzed after suitable dilution to determine concentration of drug dissolved using UV-VIS spectrophotometer 4.
The solubility study was carried out in triplicate and the observations were given in Table 4. An excess quantity of drug was added to a series of stoppered conical flasks containing 10 ml of phosphate buffer solutions of varying pH until saturated solution was obtained.
These suspensions were filtered through Whatman filter paper No. The solubility study was carried out in triplicate and the results were shown in Table 5.
Solubility Studies using Hydrotropes: An excess quantity of drug was added to a series of stoppered solubilizatiln flasks containing 10 ml of hydrotropic solutions until saturated solution was obtained. Aliquots of filtrate obtained were diluted with suitable quantity of required solvent and analyzed using UV spectrophotometer at nm.
The solubility study was carried out in triplicate and observations were shown in Table 6. Solubility Enhancement Ratio Determination: Solubility enhancement hydrotropci is another parameter that determines hydrotropc extent to which the drug is soluble in a particular solvent compared to that of water.
The solubility enhancement ratios for drug in different hydrotropic solutions were calculated and solubilizatin results were shown in Table 7. UV spectroscopic analysis for the drug was performed and the maximum absorption i.
UV analysis was carried out using 0. The drug spectrum was shown in Fig. Preparation of Standard Curve of Lumefantrine in 0. Calibration curve in of Lumefantrine was plotted using 0. The linear standard curve of Lumefantrine including the graph equation was depicted in Fig. The characteristic peaks attributable to various functional groups present in drug molecule were recorded in Table 2.
The peaks which were observed were in the corresponding range of standard peak for the respective functional group. Hence the results reveal that the sample refers to Lumefantrine structure. All the peaks values were found to be near the standard values to confirm the purity of the solubilizattion molecule. The results of qualitative solubility of Lumefantrine shown in Table 3 reveal that the drug is freely soluble in dichloromethane, ethyl acetate and chloroform.
The quantitative solubility of Lumefantrine determined in different solvents was illustrated in Table 4. The pH dependent solubility of Lumefantrine in different phosphate buffers ranging from pH 1. Lumefantrine was found to be more soluble at lower pH indicating basic nature of drug. Solubility of Lumefantine in water was 0. Hydrotropes or hydrotropic agents are molecules having planar hydrotropic structure brought into solution by a polar group.
Hence it seems rational hydrrotropic propose that molecules with a planar hydrophobic part hydrotrpic a polar group, hyxrotropic is not necessarily anionic, can act as hydrotropic agent The results of hydrotropic solubilization of Lumefantrine were given in Table 6.
Solubility of Lumefantrine in various hydrotropes was also represented in graphical form in Fig. Solubility enhancement ratio for Lumefantrine was determined and the results were shown in Table 7. It can be concluded that the concept of hydrotropic solubilization technique is novel, safe, eco-friendly and economic for enhancing bioavailability of poorly water-soluble drugs.
Actually, low aqueous solubility was the major concern for Lumefantrine; hence by the use of hydrotropic solubilization technique not only solubility, dissolution rate increased but also there would be good scope of increase in bioavailability of Lumefantrine. As a result, daily dose, frequency of administration as well other side effects related to Lumefantrine would be minimized to a great extent.
The authors are grateful to Department of Pharmaceutics, Swami Vivekanand College of Pharmacy for providing the facilities to perform research work and they also declare that they have no conflict of interest. Council of Science and TechnologyBhopal for funding this project work.
Agrawal S and Kasturi M: A promising technique to enhance solubility of poorly water soluble drug lumefantrine. Int J Pharm Sci Res ; 9 1: Article Information Sr No: Solubility enhancement ratio was calculated by using following formula: The authors have no conflict of interest.
Biochem Z ; Solubility enhancement techniques with special emphasis on hydrotrophy. World Journal of Pharmaceutical Research ; 3 4: Hydrotropic solubilization of nimesulide for parenteral administration.
International Journal of Pharmaceutics ; Solubility Enhancement of Norfloxacin by Hydrotropy Technique. International Journal of Pharmacy and Pharmaceutical Sciences ; 6 8: Solubility enhancement of candesartan cilexetil by using different hydrotropic agents.
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European Journal of Pharmaceutical and Medical Research ; 2 1: Solubility enhancement of theophylline drug using different solubilization techniques. International Journal of Pharmacology and Clinical Sciences solubilizatjon 2 1: Solubility enhancement of ibuprofen using hydrotropic agents. International Journal of Pharmacy and Life Sciences ; 2 2: Enhanced solubility study of candesartan cilexitil using different hydrotropic agent.
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