The authors have no direct financial relationships with any other commercial identities mentioned in the paper. Acknowledgment The authors would like to thank Brigit Hotz for her outstanding skillful support and assistance during animal studies.
As a most discussed but still
not completely resolved issue, solubility or dissolution enhancement techniques remain the most vibrant field for the researchers in formulation science. Solubility and dissolution are the core concepts of any physical or chemical science including biopharmaceutical and pharmacokinetic considerations in therapy of any medicine. The solubility/dissolution behavior of a drug is key determinant to its oral bioavailability, #Selleck ABT 888 keyword# the latest frequency being the rate-limiting step of absorption of drugs from the gastrointestinal tract. As a result, more than Inhibitors,research,lifescience,medical 40% of new candidates entering drug development pipeline fail because of nonoptimal biopharmaceutical properties [1]. Over the years, various techniques have been employed to enhance the dissolution profile and, in turn, the absorption efficiency and bioavailability of water insoluble drugs and/or liquid lipophilic medication [2]. Several researchers have shown that the liquisolid technique is the most promising method for promoting dissolution rate of poorly water-soluble drugs [3–5]. The liquisolid technology is described Inhibitors,research,lifescience,medical by Spireas as liquid may be transformed into a free-flowing,
readily compressible, and apparently dry powder by simple physical blending with selected excipients named the carrier and coating material (Figure 1). A liquid lipophilic drug can be converted Inhibitors,research,lifescience,medical into liquisolid system
without being further modified. On the other hand, if a solid water-insoluble drug is formulated, it should be initially dissolved or suspended Inhibitors,research,lifescience,medical in suitable nonvolatile solvent system to produce drug solution or drug suspension of desired concentration. Inert, preferably water-miscible organic solvent systems with high boiling point and a not highly viscous organic solvent system such as propylene glycol, liquid polyethylene glycols, polysorbates, fixed oils, or glycerine are best suitable as liquid vehicles [5]. Figure 1 Schematic representation of liquisolid systems. Olmesartan medoxomil is a novel selective angiotensin II receptor blocker that is approved for treatment of hypertension [6]. It is a prodrug rapidly deesterified during absorption from the gastrointestinal Calpain tract to produce an active metabolite, olmesartan [7]. However, the oral bioavailability of olmesartan medoxomil is only 26% in healthy humans due to low solubility in water and unfavorable breakage of the ester drug to a poorly permeable parent molecule in the gastrointestinal fluids. Olmesartan dose dependently reduces the blood pressure through arterial vasodilation and reduced sodium retention, as do other angiotensin receptor blockers [8].