Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation.

BACKGROUND: As a result of its very low water solubility, propofol is generally presented as a lipid-based formulation with well-characterized limitations. METHODS: Propofol (99.7%) was added directly to an aqueous solution of poly(N-vinyl-2-pyrrolidone)-block-poly(D,L-lactide)copolymers (PVP-PLA) block copolymers and stirred in order to obtain a clear solution. This formulation was filtered sterile and then lyophilized to its solid form Propofol-PM (propofol polymeric micelle) which reconstitutes to a propofol 1%w/v (10 mg ml(-1)) clear aqueous solution of 30-60 nm propofol-containing micelles. Population pharmacokinetic data from whole blood and plasma were obtained by administering reconstituted Propofol-PM formulations and a 1% oil in water formulation, Diprivan to male Sprague-Dawley rats (n = 40) at a dose of 10 mg kg(-1). Preliminary recovery data were obtained from a further small study. RESULTS: The pharmacokinetics were best described using a two-compartment mamillary population model, which incorporated sample matrix (blood or plasma) and propofol formulation (Diprivan) or Propofol-PM) as covariates. Sample matrix was applied to all structural model parameters as a dichotomous covariate. An influence of propofol formulation was observed for all parameters (excluding distributional clearance) but only when plasma was used for propofol quantification. In this preliminary pharmacodynamic study, there was no statistically significant difference in the timing of the recovery endpoints between the Propofol-PM formulation and Diprivan groups. CONCLUSIONS: Propofol-PM formulations produce anaesthesia in rats. Whole blood pharmacokinetics of Propofol-PM did not differ from those observed with Diprivan.

Structure-properties relationship in cross-linked high-amylose starch for use in controlled drug release.

Cross-linked high-amylose starch (CLHAS), obtained by high-amylose starch cross-linking, was recently introduced as an excipient (Contramid) for monolithic dosage forms that are able to control drug release over 18-24 h. These control properties are related to tablet swelling and are strongly dependent on the degree of the cross-linking of CLHAS. The permeability of solutes through CLHAS hydrogels depends on the chemical structure of the polymer. The aim of this study was to obtain a better understanding of how modifications in CLHAS molecular structures at the level of long-range and short-range order during the cross-linking and processing conditions relate to the release properties of the CLHAS matrices. Structural parameters such as crystallinity contribute significantly to the physical and mechanical aspects of starch products. X-ray diffractometry, FTIR spectroscopy, dissolution tests in vitro, and mechanical hardness (of dry tablets) were found to be sensitive to the cross-linking degree (cld) variation. Best release properties and highest mechanical hardness were obtained from CLHAS matrices with low-to-moderate crystallinity, where the V- and the B-type structures coexist with amorphous regions. X-ray and FTIR profiles of dry CLHAS powders were found to be predictive for release properties of CLHAS tablets.