7 research outputs found
Relevance of Rheological Properties of Sodium Alginate in Solution to Calcium Alginate Gel Properties
Abstract. The purpose of this study is to determine whether sodium alginate solutions' rheological parameters are meaningful relative to sodium alginate's use in the formulation of calcium alginate gels. Calcium alginate gels were prepared from six different grades of sodium alginate (FMC Biopolymer), one of which was available in ten batches. Cylindrical gel samples were prepared from each of the gels and subjected to compression to fracture on an Instron Universal Testing Machine, equipped with a 1-kN load cell, at a cross-head speed of 120 mm/min. Among the grades with similar % G, (grades 1, 3, and 4), there is a significant correlation between deformation work (L E ) and apparent viscosity (η app ). However, the results for the partial correlation analysis for all six grades of sodium alginate show that L E is significantly correlated with % G, but not with the rheological properties of the sodium alginate solutions. Studies of the ten batches of one grade of sodium alginate show that η app of their solutions did not correlate with L E while tan δ was significantly, but minimally, correlated to L E . These results suggest that other factors-polydispersity and the randomness of guluronic acid sequencing-are likely to influence the mechanical properties of the resultant gels. In summary, the rheological properties of solutions for different grades of sodium alginate are not indicative of the resultant gel properties. Interbatch differences in the rheological behavior for one specific grade of sodium alginate were insufficient to predict the corresponding calcium alginate gel's mechanical properties
A novel nanomedicine against arthritis: Targeted camptothecin phospholipid micelles.
A novel nanomedicine against arthritis: Targeted camptothecin phospholipid micelles
Mitigation of Adverse Clinical Events of a Narrow Target Therapeutic Index Compound through Modified Release Formulation Design: An in Vitro, in Vivo, in Silico, and Clinical Pharmacokinetic Analysis
BMS-914392 is a tricyclic pyranoquinoline
BCS class 2 weak base
that demonstrates high solubility in low pH environments. Initial
clinical studies indicated that rapid release of high dose BMS-914392
led to transient adverse events associated with peak plasma concentrations.
A modified release (MR) formulation strategy was proposed to suppress
the peak blood concentration and maintain total exposure to overcome
the adverse effects. Three modified release prototype formulations
were developed and tested via a USP 3 dissolution method to verify
that each formulation can effectively slow the release of BMS-914392.
A pharmacokinetic (PK) absorption model was employed to guide the
formulation development and selection. Simulations showed good agreement
with plasma levels measured after oral dosing in dogs. Identification
of key formulation factors to achieve release rates suitable for blunting
peak blood levels without diminishing exposure were achieved through
combined preclinical data and use of GastroPlus simulations. PK absorption
model refinements based on phase 1 data, dog pharmacokinetic results,
and in vitro data provided reliable predictions of human absorption
profiles and variability in patients. All three prototype formulations
demonstrated lower maximum plasma concentrations of BMS-914392 and
maintained satisfactory relative bioavailability. Both the PK absorption
model and subsequent clinical data indicated that an acidified hydrophilic
matrix MR formulation had the greatest potential to reduce the incidence
of adverse events and showed the best exposure profile in fasted state
healthy subjects with and without famotidine coadministration. The
risk based development process achieved successful screening and selection
of a suitable modified release formulation to enable clinical efficacy
trials