There are many reasons for this market deficiency including formulation difficulties and identification of suitable existing and new APIs amenable to liquid/soluble formulations.
On the contrary, heuristic methods are suitable for stochastic global search, free from problem formulation difficulties and can escape from premature local optimal.
This review outlines SDLFs as one of the most promising approaches to overcome the formulation difficulties of these hydrophobic/lipophilic drugs.
However, formulation difficulties have halted its clinical development.
However, geldanamycins have several limitations, including poor solubility, formulation difficulties, hepatotoxicity and extensive metabolism by polymorphic enzymes, along with drug efflux by P-glycoprotein (Kelland et al, 1999; Eiseman et al, 2005; Brough et al, 2008; Eccles et al, 2008).
(2, 3) However, geldanamycin derivatives have several limitations, including poor solubility, formulation difficulties, and severe hepatotoxicity in clinical settings,(4– 6) which have prompted development of next generation synthetic HSP90 inhibitors including NVP-AUY922 (aUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor that inhibits the ATPase activity of HSP90.
However, geldanamycins have several limitations, including poor solubility, formulation difficulties, hepatotoxicity, and extensive metabolism by polymorphic enzymes, along with drug efflux by P-glycoprotein; therefore, efforts to design small synthetic inhibitors of Hsp90 with improved bioavailability and lower toxicity are devoted [ 288– 291].
This review is focused on the key challenges of siRNA therapeutics, with special attention on the faced obstacles and on the formulation-related difficulties, providing a list of requirements needed for obtaining an ideal carrier for siRNA.
You have to step back and ask, Is it necessary?" This antediluvian formulation underlined the difficulty of Gawker's task in defending itself from a privacy claim as opposed to a libel suit; the defendants were forced to defend their taste rather than their accuracy.
Gauthier himself points out that his formulation runs into difficulty in dealing with situations in which a person has assumed a certain social role, e.g., the role of a life-guard that is, in part, defined by positive duties vis-à-vis others.
