Effect of Molecules' Physicochemical Properties on Whey Protein/Alginate Hydrogel Rheology, Microstructure and Release Profile.

The encapsulation of molecules with different physicochemical properties (theophylline, blue dextran, salicylic acid and insulin) in whey protein (WP) and alginate (ALG) microparticles (MP) for oral administration was studied. MP based on WP/ALG were prepared by a cold gelation technique and coated with WP solution after reticulation. Molecules influenced polymer solution viscosity and elasticity, resulting in differences regarding encapsulation efficiency (from 23 to 100%), MP structure and swelling (>10%) and in terms of pH tested. Molecule release was due to diffusion and/or erosion of MP and was very dependent on the substance encapsulated. All the loaded MP were successfully coated, but variation in coating thickness (from 68 to 146 µm) and function of the molecules encapsulated resulted in differences in molecule release (5 to 80% in 1 h). Gel rheology modification, due to interactions between WP, ALG, calcium and other substances, was responsible for the highlighted differences. Measuring rheologic parameters before extrusion and reticulation appeared to be one of the most important aspects to study in order to successfully develop a vector with optimal biopharmaceutical properties. Our vector seems to be more appropriate for anionic high-molecular-weight substances, leading to high viscosity and elasticity and to MP enabling gastroresistance and controlled release of molecules at intestinal pH.

Effect of unconventional curing conditions and storage on pellets coated with Aquacoat ECD.

PURPOSE: Purpose of this study was to develop storage stable pellets coated with the aqueous ethylcellulose dispersion Aquacoat ECD. METHODS: The influence of accelerated curing/storage conditions on the release behavior of Aquacoat/HPMC-coated drug pellets were investigated as a function of various formulations (sealing, plasticizer content, and pore-former type/amount) and process parameters (process humidity, thermal curing, and organic processing). RESULTS: Conventionally cured Aquacoat/hydroxypropyl methylcellulose- coated pellets were storage stable at ambient conditions and 25 degrees C/60% relative humidity (RH) but showed a decreasing drug release at 40 degrees C/75% RH, which is a required test condition according to ICH guidelines. CONCLUSION: Only organic processing of dried Aquacoat or unconventionally harsh curing conditions (60 degrees C/75% RH or 80 degrees C) improved the storage stability of Aquacoat-coated pellets at accelerated conditions.

Microencapsulation of low molecular weight heparin into polymeric particles designed with biodegradable and nonbiodegradable polycationic polymers.

Owing to its lack of oral absorption, heparin has to be administered parenterally. However, parental administration has negative aspects such as multiple injections, possible infection, patient inconvenience, and high cost. Now, low molecular weight heparin (LMWH) is taking part in antithrombotic treatment and is proven to confer more advantages than unfractionated heparin. The aim of our present study was to formulate, by the w/o/w emulsification process, LMWH microparticles as potential oral carriers prepared with biodegradable (poly-epsilon-caprolactone and poly-lactic-co-glycolic acid) and nonbiodegradable polycationic polymers (Eudragit RS and RL), used alone or blended. The encapsulation efficiency ranged from 16 to 47% and was highly dependent on the presence of the positively charged polymers. In the same way, a low in vitro LMWH release was observed when Eudragit polymers composed totally or partially the polymeric matrix, compared with biodegradable polymers exhibiting higher LMWH release (40 and 60%). For each formulation, LMWH released from microparticles preserved its biological activity as shown by the antifactor Xa activity. Experiments performed with fluorescein-labeled LMWH showed the drug distribution in microparticles and may give information about the mechanisms controlling LMWH encapsulation and release.

Low molecular weight heparin-loaded polymeric nanoparticles: formulation, characterization, and release characteristics.

The aim of the present work was to investigate the preparation of low molecular weight heparin (LMWH) nanoparticles (NP) as potential oral heparin carriers. The NP were formulated using an ultrasound probe by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation with two biodegradable polymers [poly-epsilon-caprolactone, PCL and poly(D,L-lactic-co-glycolic acid) 50/50, PLGA] and two non-biodegradable positively charged polymers (Eudragit RS and RL) used alone or in combination. The mean diameter of LMWH-loaded NP ranged from 240 to 490 nm and was dependent on the reduced viscosity of the polymeric organic solution. The surface potential of LMWH NP prepared with Eudragit polymers used alone or blended with PCL and PLGA was changed dramatically from strong positive values obtained with unloaded NP to negative values. The highest encapsulation efficiencies were observed when Eudragit polymers took part in the composition of the polymeric matrix, compared with PCL and PLGA NP exhibiting low LMWH entrapment. The in vitro LMWH release in phosphate buffer from all formulations ranged from 10 to 25% and was more important (two- to threefold) when esterase was added into the dissolution medium. The in vitro biological activity of released LMWH, determined by the anti-factor Xa activity with a chromogenic substrate, was preserved after the encapsulation process, making these NP good candidates for oral administration.

Preparation and characterization of heparin-loaded polymeric microparticles.

Microparticles containing heparin were prepared by a water-in-oil-in-water emulsification and evaporation process with pure or blends of biodegradable (poly-epsilon-caprolactone and poly(D,L-lactic-co-glycolic acid)) and of positively-charged non-biodegradable (Eudragit RS and RL) polymers. The influence of polymers and some excipients (gelatin A and B, NaCl) on the particle size, the morphology, the heparin encapsulation rate as well as the in vitro drug release was investigated. The diameter of the microparticles prepared with the various polymers ranged from 80 to 130 microns and was found to increase significantly with the addition of gelatin A into the internal aqueous phase. Microparticles prepared with Eudragit RS and RL exhibited higher drug entrapment efficiency (49 and 80% respectively) but lower drug release within 24 h (17 and 3.5% respectively) than those prepared with PCL and PLAGA. The use of blends of two polymers in the organic phase was found to modify the drug entrapment as well as the heparin release kinetics compared with microparticles prepared with a single polymer. In addition, microparticles prepared with gelatin A showed higher entrapment efficiency, but a significant initial burst effect was observed during the heparin release. The in vitro biological activity of heparin released from the formulations affording a suitable drug release has been tested by measuring the anti-Xa activity by a colorimetric assay with a chromogenic substrate. The results confirmed that heparin remained unaltered after the entrapment process.

The reliability of patient positioning for evaluating static radiologic parameters of the human pelvis.

OBJECTIVE: To determine the reproducibility of patient positioning on radiographically evaluated static configurations of the human pelvis. DESIGN: Repeat anteroposterior radiography of the human pelvis was performed in vivo. Comparative examinations were performed after 1 hr in one subject pool. A second sample underwent repeat examination after a mean of 18 days. SETTING: Outpatient private practice chiropractic clinic. SUBJECTS: Thirty-seven relatively asymptomatic subjects participated in the experiment. MAIN OUTCOME MEASURES: Millimetric evaluations were made for leg length inequality, right/left sacral discrepancies and right/left innominate differences. The null hypothesis was that the difference of the measurements from the two radiographs would be equal to zero. A paired t-test was used to analyze if there were any significant differences. The mean measured difference in millimeters and correlation coefficients were also determined for each variable. RESULTS: Individual variations for several roentgenometric parameters, including leg length inequality and pelvic torsion, did not reach statistical significance (p > .05) although minor millimetric discrepancies were recorded. Correlation coefficients, in most cases, were relatively high. CONCLUSION: A subject can be reliably positioned for repeat anteroposterior pelvic radiography for both 1 hr and 18-day intervals. The methodology described has applicability to full spine radiography when roentgenometric parameters of the pelvis are scrutinized.