ABSTRACT
Aim: 1) To increase water solubility of indomethacin drug using mixed solvency approach. 2) To employ use of non toxic solubilizers for increasing solubility of a poorly water soluble drug. Study Design: Trial and error based experimental study. Place and Duration of Study: School of Pharmacy, Devi Ahilya Vishwavidyalaya, UTD, Takshashila Campus, Indore, India and College of Pharmacy, IPS Academy, Indore, India between Jan. 2011 and June. 2012. Methodology: By making mixed solvent (40%) blends of selected water soluble substances from the hydrotropes (urea, sodium benzoate, sodium citrate, nicotinamide); water-soluble solids (PEG- 4000, PEG-6000); and co-solvents (propylene glycol, glycerine, PEG-200, PEG-400, PEG 600) solubility studies were performed with indomethacin (model drug). On the basis of solubility studies formulation was developed. The solubilized drug and prepared formulation were characterized by ultraviolet and infrared techniques. Various properties of solution such as pH, viscosity, specific gravity and surface tension were studied. The developed formulation was studied for physical and chemical stability. Result: Aqueous solubility of drug in case of selected blends ranged from 14.55 mg/ml – 19.96 mg/ml (as compared to the solubility in distilled water 0.0464 ± 0.007 mg/ml). The enhancement in the solubility of drug in a mixed solvent containing 10% sodium benzoate, 5% sodium citrate and 25 % S cosolvent (25% S cosolvent contains PEG200, PEG 400, PEG600, Glycerine and Propylene glycol) was more than 400 fold. Prepared formulation F10 show appreciable physical and chemical stability. Conclusion: The results of this study provide guidance for developing an injectable product and strategies for improving solubility as well as stability of poorly water soluble drug using the concept of mixed solvency. The proposed technique is economical, convenient and safe. The application of mixed solvency approach in the development of formulations shall prove a boon for pharmaceutical industries.
ABSTRACT
Enhancement of solubility is one of the difficult tasks which become challenges in formulation development of orally administered drug with poor aqueous solubility. Poor water solubility of drugs often causes significant problems in producing formulations of sufficiently high bioavailability, preventing effective use of the drugs. 'Mixed-solvency ' concept is the phenomenon to increase the solubility of poorly water-soluble drugs in the aqueous solution containing blends of hydrotropic agents, co-solvents and water soluble solutes which may give synergistic enhancement effect on solubility of such drugs. In the present investigation , mixed solvency approach has been applied for the enhancement of aqueous solubility of a poorly water- soluble drugs diclofenec sodium (selected as a model drug), by making blends of randomly selected water-soluble substances from among the hydrotropic (urea, sodium acetate); water soluble solutes (PEG4000, PEG6000); and co-solvents (PEG200, PEG400). The aqueous solubility of diclofenac sodium was observed at room temperature in the randomly selected blends of solubilizers containing different combinations keeping total concentration 50%w/v constant. Diclofenec sodium have λmax 276 nm and obeys Beers Law in concentration range of 10-60 μg/ml. The results suggest that solubility of the diclofenac sodium containing blends of varying combinations was enhanced significantly using mixed solvency approach.
ABSTRACT
Enhancement of solubility is one of the difficult tasks which become challenges in formulation development of orally administered drug with poor aqueous solubility. Poor water solubility of drugs often causes significant problems in producing formulations of sufficiently high bioavailability, preventing effective use of the drugs. 'Mixed-solvency ' concept is the phenomenon to increase the solubility of poorly water-soluble drugs in the aqueous solution containing blends of hydrotropic agents, co-solvents and water soluble solutes which may give synergistic enhancement effect on solubility of such drugs. In the present investigation , mixed solvency approach has been applied for the enhancement of aqueous solubility of a poorly water- soluble drugs diclofenec sodium (selected as a model drug), by making blends of randomly selected water-soluble substances from among the hydrotropic (urea, sodium acetate); water soluble solutes (PEG4000, PEG6000); and co-solvents (PEG200, PEG400). The aqueous solubility of diclofenac sodium was observed at room temperature in the randomly selected blends of solubilizers containing different combinations keeping total concentration 50%w/v constant. Diclofenec sodium have λmax 276 nm and obeys Beers Law in concentration range of 10-60 μg/ml. The results suggest that solubility of the diclofenac sodium containing blends of varying combinations was enhanced significantly using mixed solvency approach.