Drug Optimization: Fighting Research to Achieve the Greatest Use of Darunavir

Abstract

Acquired Immunodeficiency Syndrome (AIDS) is the final stage of the disease caused by Human Immunodeficiency Virus (HIV). It attacks the defense cells of the body, leaving the body vulnerable to all kinds of diseases [1-3].Currently, treatment of HIV infection relies on the called Highly Active Antiretroviral Therapy (HAART) which proposes the combination of several drugs in a daily regimen [1,[4][5][6][7][8][9]. Therapeutic agents are divided according to their mechanism of action. Darunavir belongs to protease inhibitors such as atazanavir, fosamprenavir, indinavir, lopinavir/ritonavir, ritonavir, saquinavir, tipranavir [1,[10][11][12][13][14][15]. Darunavir: β-CyclodextrinDarunavir, an antiretroviral drug, has low solubility in water and requires administration in high doses [16,17]. So, it was complexed with β-cyclodextrin [18]. The complex has been studied and compared to free darunavir. CharacterizationDarunavir: β-cyclodextrin complex, by spectrophotometry in the infrared region, shows bands present in the free darunavir and other characteristic bands from complexation [19].The thermal studies, by thermogravimetry and differential scanning calorimetry with heat flux showed that the darunavir: β-cyclodextrin complex has a higher thermal stability than the free drug and also has characteristic behavior [19].The darunavir: β-cyclodextrin complex, by X-ray diffraction, shows crystalline form [19].These techniques can identify darunavir: β-cyclodextrin complex safely and effectively. SolubilityThe solubility of the darunavir: β-cyclodextrin complex was studied and the results were impressive and significant for science and for public health. The darunavir: β-cyclodextrin complex presented solubility 28 times higher than free darunavir in acetate buffer 0.05 M at pH 4.5, 23 times in water purified and 22 times in phosphate buffer 0.2 M at pH 6.8 [16].This study allows the use of smaller doses of the drug and therefore adverse effects are less frequent. This advantage for patients with AIDS is a great advance, since they are bodies debilitated by the virus and administer many medications daily. Analytical methodsMethod by Thin Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC) were developed for the identification and quantification of darunavir in the darunavir: β-cyclodextrin complex [20,21]. These methods were also able to identify degradation products of the complex, being considered methods indicative of stability.