EFFECT OF pH AND ORGANIC HYDROXYLATED ADDITIVES ON N-DESMETHYLDIAZEPAM SOLUBILIZATION BY NON-IONIC SURFACTANTS

Document Type : Original Article

Authors

Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt

Abstract

N-desmethyldiazepam, was solubilized in different non-ionic surfactant solutions including members of polysorbates, Myrjs, Eumulgins and Brijs at 25 and 35 C.
Polysorbate 80 was more efficient in solubilizing the drug than polysorbate 20 and Brij 35 was more efficient than Brij 58. On the other hand, Eumulgin C1000 was found to be more efficient than Eumulgin C1500 and Myri 52 was found to be more efficient than Myrj 53 and Myrj 59 respectively.
Always raising the temperature of the investigated solutions caused a positive temperature effect and a decrease in Km values.
Adjusting the pH of Eumulgin and Brij solutions caused a gradual decrease in the quantity of the drug solubilized by raising the pH from
pH 4.0 to 7.4.
Theoretical treatment to quantify the role of both the core and the capsular regions of the micelle in N-desmethyldiazepam solubilization showed that the core of the micelle plays the most important role in solubilizing the drug.
The drug was solubilized in Eumulgin and Brij series containing 5 and 10% w/v of propylene glycol, glycerol, polyethylene glycol 400 (PEG 400) and polyethylene glycol 4000 (PEG 4000). The incorporation of propylene glycol, glycerol and PEG 400 or 4000 increased the solubilizing efficiencies of the surfactants toward the drug at 25 C.
Incorporation of 5% w/v of these additives in the tested Eumulgin and Brij solutions caused an increase in the Km values of the drug and the revrese is true for 10% w/v of these additives.