title: The impact of co-solvents and the composition of experimental formulations on the pump rate of the ALZET osmotic pump.
abstract: The water-miscible co-solvents polyethylene glycol 400 (PEG400), N-methyl-2-pyrrolidone (NMP), and N, N-dimethylacetamide (DMA) exhibit the potential to increase the solubility of poorly water-soluble compounds and therefore they represent promising vehicles for compound delivery using osmotic pumps in early discovery experiments. Thus, the selected co-solvents were investigated for their compatibility with the interior of ALZET osmotic pumps. Moreover, 1-week pumps were filled with mixtures of either the co-solvents with water (60:40, v/v), with neat PEG400, or with PEG400/water mixtures of different concentrations. It was determined whether the composition of an experimental formulation could have an impact on the overall pump rate with 14C-mannitol being used as the model compound. It was found that neat PEG400 was compatible with the reservoir material, whereas NMP and DMA were tolerable only in aqueous solutions up to 60%. PEG400, NMP, and DMA mixtures with water (60:40) resulted in release rates comparable to those of water and PEG400/water mixtures of lower co-solvent concentration. Moreover, as demonstrated using the various PEG400/water mixtures, the amount of co-solvent in the formulation had no significant impact on the overall release profile. By contrast, the use of neat PEG400 resulted in a significant decrease in the pump rate.
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, CH-4070 Basel, Switzerland. beate.bittner@roche.com
authors.forename: B
authors.initials: B
authors.lastname: Bittner
authors.forename: T
authors.initials: T
authors.lastname: Thelly
authors.forename: H
authors.initials: H
authors.lastname: Isel
authors.forename: R J
authors.initials: RJ
authors.lastname: Mountfield
mesh_terms: D016503:Drug Delivery Systems; D007260:Infusion Pumps; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D012997:Solvents; D011092:Polyethylene Glycols