Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Special Issue 9 ¦ 2022 1748 Solubility Enhancement of Rifabutin by Co-solvency Approach Jyoti Maithani Kalra 1 , Kapil Kalra 2 , Vandana Pokhriyal 2 , Kashif Husaain 3 1 School of Pharmaceutical Sciences, Himgiri Zee University, Dehradun 2 Alpine College of Management & Technology, Dehradun 3 Gyan Inder Singh Institute of Professional Studies, Dehradun Email: jyotimk123@gmail.com DOI: 10.47750/pnr.2022.13.S09.210 Rifabutin is wide spectrum antimicrobial agent, effective in the treatment of infection caused by M. tuberculosis, M. avium and M. Leprae and also used in the treatment of multidrug resistant TB. Rifabutin is very poorly water soluble drug (0.19mg/ml) with high permeability. For enhancement of solubility of a hydrophobic drug has a significant role in the development of a liquid dosages form. The main purpose of this study was to improve the solubility of Rifabutin by co solvency method. Different blends were prepared by usinf different solvents and surfactants in different proportions have been used to enhance the solubility of Rifabutin like water, phosphate buffer, ethanol, propylene glycol and PEG 400, Tween 80 and Brij 35. In thisit was found that the blend 90% PEG and 10% co solvents (ethanol and propylene glycol) give highest solubility and among the surfactant systems, Tween 80 had shown enhanced solubility of Rifabutin. Solubility of rifabutin was determined by preparing saturated solutions of rifabutin in pure solvents and in mixture of co solvents with or without surfactants. It observed that the blend of 90% PEG and 10% ethanol and propylene glycol had shown the better improvement of solubility when compared with the other solvents and co solvents as it caused a noteworthy enhancement in solubility of Rifabutin that was 1.6803 mg/ml.The above observations lead to propose that the addition of small amount of polar solvent enhances the solubility of drug.Thus, the study generated an important array of data to compare the effect of these cosolvents on the aqueous solubility of rifabutin. Keywords: Co solvency, rifabutin, solubility enhancement, surfactants. 1. INTRODUCTION Solubility is defined as the highest portion of a drug molecule that will be totally dissolved in a given solvent at a fixed temperature and pressure. Solubility of the drug is a crucial characteristic in order to get the effective concentration of drug in the blood circulation for their pharmacological response. At present time about 40% of newly discovered drug molecules are poorly water soluble or highly lipophilic in nature. The poor solubility of a drug is a very complicated issue for drug delivery. Most of the pharmaceutical companies are trying to increase the solubility of poorly water soluble drugs. A drug with low solubility having problem in their bioavailability and also affect their pharmacological action and amount of drug used. 1 Oral absorption of a drug, enough bioavailability and all pharmacokinetic profile of a drug molecule into the body is a crucial challenge in the oral dosages form development of newly found drug molecule. Bioavailability of a drug, absorption of a drug and the solubility of a drug ultimately affects the pharmacological effectiveness of drug molecule. So in simple words we can say that the therapeutic effectiveness of drug molecule depends upon its solubility.2 Thus solubility of a drug molecule is considered as a most important factor to obtain the desired amount of drug in the blood circulation so that the drug can give its pharmacological effect. Around one-fourth of the newly discovered drugs listed in the united state pharmacopoeia are comes into the category of poorly water-soluble drugs. The oral delivery of the new drugs can be affected by the solubility issues and also the delivery of many existing drugs. Poorly water soluble drugs cause many difficulties in the formulation development, such as limited choices of delivery of drug and a very complex dissolution testing with inadequate correlation to the in vivoabsorption. Due to the poor solubility drug cant reached into the systemic circulation and cause problem in attaining expected in vivo/in vitro correlations. However, various leading pharmaceutical companies have been able to triumph over technical hitches with very slightly aqueous soluble drugs, those with aqueous sol ubility of less than 0.1 mg/mL present some unique challenges. These drugs are particularly good candidates for advanced solubilisation technologies developed by