fumarates and calcium-phosphate--dibasic--anhydrous

To develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status.. A nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the HPMC matrix tablets in different locations of the gastrointestinal tract, determined by magnetic marker monitoring. In each gastrointestinal segment the pH was set to physiological values and mechanical stress was estimated in USP2 apparatus rotation speed equivalent.. Erosion was best described by a Michaelis-Menten type model. The maximal HPMC release rate (V. The in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets.

Topics: Adult; Calcium Phosphates; Chemistry, Pharmaceutical; Colon; Computer Simulation; Delayed-Action Preparations; Fasting; Ferric Compounds; Fumarates; Gastric Mucosa; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives; Intestine, Small; Male; Postprandial Period; Solubility; Stress, Mechanical; Tablets

We investigated the crosslinking characteristics of an injectable composite paste of poly(propylene fumarate) (PPF), N-vinyl pyrrolidinone (N-VP), benzoyl peroxide (BP), sodium chloride (NaCl), and beta-tricalcium phosphate (beta-TCP). We examined the effects of PPF molecular weight, N-VP/PPF ratio, BP/PPF ratio, and NaCl weight percent on the crosslinking temperature, heat release upon crosslinking, gel point, and the composite compressive strength and modulus. The maximum crosslinking temperature did not vary widely among formulations, with the absolute values falling between 38 degrees and 48 degrees C, which was much lower than that of 94 degrees C for poly(methyl methacrylate) bone cement controls tested under the same conditions. The total heat released upon crosslinking was decreased by an increase in PPF molecular weight and a decrease in N-VP/PPF ratio. The gel point was affected strongly by the PPF molecular weight, with a decrease in PPF molecular weight more rapidly leading to a gel point. An increase in initiator concentration had the same effect to a lesser degree. The time frame for curing was varied from 1-121 min, allowing the composite to be tailored to specific applications. The compressive strength and compressive modulus values increased with decreasing N-VP/PPF, increasing NaCl content, and increasing BP/PPF ratio. For all formulations, the compressive strength values fell between 1 and 12 MPa, and the compressive modulus values fell between 23 and 265 MPa. These data suggest that injectable PPF/beta-TCP pastes can be prepared with handling characteristics appropriate for clinical orthopedic applications and that the mechanical properties of the cured composites are suitable for trabecular bone replacement.

Topics: Biodegradation, Environmental; Bone Cements; Calcium Phosphates; Calorimetry, Differential Scanning; Chemical Phenomena; Chemistry, Physical; Compressive Strength; Cross-Linking Reagents; Fumarates; Gels; Materials Testing; Molecular Weight; Ointments; Polypropylenes; Temperature