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.

Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems.

In-situ forming drug delivery systems are prepared by dissolving a drug and a biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible organic solvent (In-situ implant, ISI) or further emulsified into an external phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA and the drug is a major concern. In this study, the stability of PLGA and leuprolide acetate in the in-situ forming systems and lyophilized sponges was investigated. The degradation of PLGA increased with increasing storage temperature and water content in the biocompatible solvents. A faster degradation occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl acetate). The presence of leuprolide acetate significantly accelerated PLGA degradation, especially in solution state. PLGA was stable in oily suspensions at 4 degrees C and degraded only slightly faster than solid powder at 25 degrees C. No interaction between the oils and the PLGA was observed as indicated by an unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4 degrees C after 150 days in water and saturated sodium chloride solution. The degradation was slower in saturated sodium chloride solution than in water at 25 degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA stability negatively. However, lidocaine significantly enhanced the polymer degradation in the sponges. Finally, leuprolide acetate was chemically stable in the sponges, the oils and the polymer solutions in suspension state, but unstable (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C and 40 degrees C.

[Pentoxifylline inhibits secretion of O2- and TNF-alpha by alveolar macrophages in patients with sarcoidosis]. / Pentoxifyllin hemmt die Sekretion von O2- und TNF-alpha durch Alveolarmakrophagen bei Patienten mit Sarkoidose.

Reactive oxygen species (ROS) and cytokines like tumor necrosis factor-alpha (TNF-alpha) play a crucial role as inflammatory mediators in pulmonary sarcoidosis. We examined the antiinflammatory effect of pentoxifylline (POF) on alveolar macrophages (AM) of patients with sarcoidosis in vitro. We could demonstrate that POF (above 4.10(-4) M) inhibited the secretion of superoxide anion and TNF-alpha by AM in a dose-dependent manner via a prostaglandin synthesis-dependent mechanism that was independent of the glucocorticoid receptor. POF is an interesting immunomodulating substance that should be further evaluated in clinical trials.