Gastrointestinal absorption of Heparin by lipidization or coadministration with penetration enhancers

A review with 93 references. Heparins are high molecular weight, hydrophilic polyanions, which are unstable under acidic conditions; and therefore they exhibit poor oral bioavailability. Consequently they must be administered via the parenteral route which is expensive, inconvenient, and limits use by outpatients. The development of an oral form of heparin is warranted. This review examined the literature, mostly published between January 2000 and January 2005, pertaining to the gastrointestinal absorption of heparin by lipidization or coadministration with penetration enhancers. A lipidization strategy that was examined involved conjugation of low molecular weight heparin with deoxycholic acid. The majority of studies examined the ability of different formulations, typically utilizing penetration enhancers, to improve heparin bioavailability. The penetration enhancers used included fatty acids, Labrasol™, Gelucire 44/14™, polycationic lipophilic-core dendrons, saponins, mono-N-carboxymethyl chitosan, Carbopol® 934P, a combination of thiolated polycarbophil and glutathione, polymeric nanoparticles, polymeric microparticles, sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC), and sodium N-[10-(2-hydroxybenzoyl)amino]decanoate (SNAD). The variety of models used and doses of heparin/penetration enhancers applied, however, made it difficult to compare the results between studies. Nevertheless, all of the reviewed drug delivery systems showed therapeutic value and confirmation of the promising results obtained from animal studies, by progression to clinical trials, is necessary. Overall, progress has been made in the quest for an oral heparin formulation.

The relationship of cervical joint position error to balance and eye movement disturbances in persistent whiplash

Cervical joint position error (JPE) has been used as a measure of cervical afferent input to detect disturbances in sensori-motor control as a possible contributor to a neck pain syndrome. This study aimed to investigate the relationship between cervical JPE, balance and eye movement control. It was of particular interest whether assessment of cervical ME alone was sufficient to signal the presence of disturbances in the two other tests. One hundred subjects with persistent whiplash-associated disorders (WADs) and 40 healthy controls subjects were assessed on measures of cervical JPE, standing balance and the smooth pursuit neck torsion test (SPNT). The results indicated that over all subjects, significant but weak-to-moderate correlations existed between all comfortable stance balance tests and both the SPNT and rotation cervical ME tests. A weak correlation was found between the SPNT and right rotation cervical JPE. An abnormal rotation cervical JPE score had a high positive prediction value (88%) but low sensitivity (60%) and specificity (54%) to determine abnormality in balance and or SPNT test. The results suggest that in patients with persistent WAD, it is not sufficient to measure ME alone. All three measures are required to identify disturbances in the postural control system. (C) 2005 Elsevier Ltd. All rights reserved.