Development of self-microemulsifying bilayer tablets for pH-independent fast release of candesartan cilexetil.

The aim of this study was to design self-microemulsifying tablets for pH-independent fast release of poorly soluble candesartan cilexetil (CDC). To improve the solubility of CDC, a self-microemulsifying drug delivery system (SMEDDS) was prepared composed of Capryol 90, Tween 80 and tetraglycol at a ratio of 5:35:60. Drug containing SMEDDS was adsorbed onto Fujicalin and Neusilin UFL2, respectively, used as solidification carriers and subsequently compressed into tablets (self-microemulsifying tablet, SMET). SMET using Fujicalin exhibited immediate CDC release in pH 1.2 medium while Neusilin UFL2-based SMET showed fast release, especially at pH 6.5. Thus, optimized SMET could be produced with one layer of Fujicalin and the other layer with Neusilin UFL2, demonstrating CDC release of 75% of the initial dose within 15 min in all pH conditions (1.2, 4.5, and 6.5). The average diameter of emulsion droplets formed from SMET was less than 200 nm. It was thus expected that Fujicalin and Neusilin UFL2-based bi-layer SMET would overcome low oral bioavailability of CDC due to its limited solubility at physiological pH conditions in the gastrointestinal tract.

Pharmacologically active metabolites of currently marketed drugs: potential resources for new drug discovery and development.

Biotransformation is the major clearance mechanism of therapeutic agents from the body. Biotransformation is known not only to facilitate the elimination of drugs by changing the molecular structure to more hydrophilic, but also lead to pharmacological inactivation of therapeutic compounds. However, in some cases, the biotransformation of drugs can lead to the generation of pharmacologically active metabolites, responsible for the pharmacological actions. This review provides an update of the kinds of pharmacologically active metabolites and some of their individual pharmacological and pharmacokinetic aspects, and describes their importance as resources for drug discovery and development.

Self-microemulsifying formulation-based oral solution of coenzyme Q10.

The goal of our investigation was to develop oral solution of coenzyme Q10 (CoQ10) by using self-emulsifying systems. CoQ10 is practically insoluble in water. Therefore, it is difficult to develop oral solution of CoQ10. To solubilize CoQ10 and to develop it as oral solution, self-emulsifying systems consisted of oil, surfactant and co-surfactant were studied and using the self-emulsifying system chosen, oral solution was developed. After the evaluation of solubilizing abilities of various oils and surfactants, the self-emulsifying system consisted of acetylated monoglyceride (AM) as oil, polyoxyethylene (20) sorbitan monolaurate (P2SM) as surfactant and propylene glycol laurate (PGL) as co-surfactant, was chosen because the emulsions prepared by that system showed spontaneous emulsification and transparent appearance. All of these components could be used for the development of functional foods. Finally, a CoQ10 solution with concentrations of 100 mg/70 ml and 100 mg/100 ml could successfully be developed by the addition of water to one milliliter of self-emulsifying system consisted of AM (10%), P2SM (70%) and PGL (20%) along with 100 mg of CoQ10. This oral solution formulation was stable for more than one month.