The compound exhibits potent

in vitro antibacterial activity against a broad range of Gram-positive bacteria. The minimum inhibitory concentration (MIC) values evaluated for the compound were in nano-molar range. In in vivo studies of PM181104 in a BALB/c murine septicemia model, the compound displayed 100% effective dose (ED100) value of 2.5 mg kg−1 of body weight against MRSA and 10.0 mg kg−1 against VRE, and in tissue or organ-specific infection models showed reduction in bacterial titer comparable to standard antibiotics [5] and [7]. In the current studies, suitable intravenous (i.v) formulation development approaches have been explored. We consider that the i.v. route of administration facilitates complete bioavailability and rapid action to treat the systemic infections associated with the Gram-positive pathogens. True to the behavior ABT-888 supplier of naturally occurring thiazolyl peptide antibiotics, PM181104 too exhibited poor aqueous solubility. To overcome such difficulty, we made an effort

to develop an i.v. formulation using a non-ionic surfactant with co-solvent combination approach [8]. The advantage click here of this approach is that the combination of surfactant and polymer may provide better protection against solvent-mediated transformation than the surfactant or polymer alone [9]. However, in order to avoid the possible side effects such as anaphylactic response and vascular irritability which may be caused by surfactants, it is far safe to reduce the types and stoichiometric concentration of the stabilizers used [10] and [11]. Indeed, there is

a set-in guideline by the FDA for choosing an inactive ingredient [36]. Therefore, the major focus of our studies was to formulate a dosage form that exhibits in vivo efficacy with a scope to minimize the excipient composition to an acceptable extent. Initial attempts to achieve maximum drug exposure levels, also inherently delivered a proportionately higher concentration of excipients. Hence, there was a scope to bring down the excipient levels in the defined dosage delivery. Towards this effort, we embarked upon studies involving the stoichiometric Aurora Kinase alteration of two of the excipients namely, T-80 and PEG 400 which fall under generally recognized as safe (GRAS) category, and comparing their associated pharmacokinetics outcomes. We also evaluated the effect of stiochiometric variations in these excipients on the osmolarity, pH as well as particle size of the drug and its implications on in vivo situation. These efforts resulted in the identification of an in vivo efficacious formulation suitable for parenteral administration. The current paper describes the detailed studies of the development of an in vivo efficacious formulation using T-80 and PEG 400 and effect of stiochiometric variation of these excipients on osmolarity, pH, particle size of the drug and the associated effect on pharmacokinetics outcomes. PM181104 was isolated and characterized in-house [5].