Solid lipid extrudates as sustained-release matrices: the effect of surface structure on drug release properties.

The study focused on the structural characterization of sustained-release lipid matrices prepared by solid lipid extrusion. Drug-containing lipid extrudates were locally analyzed in order to identify differences between the chemical and structural composition of surface and core elements. Independent of the lipid the dissolution from the outer extrudate surfaces was slower compared with dissolution from surfaces prepared by cutting the extrudate. The burst effect was higher for the cross-sections indicating more drug was exposed on these surfaces. The release from glycerol trimyristate (Dynasan 114) extrudates was slower compared with glycerol palmitostearate (Precirol ATO 5) extrudates. By solid-state analysis using DSC, ATR-FTIR and SEM measurements the differences between surface material and core material could be attributed mainly to morphological differences. Chemical differences between the core and the outer surface were not relevant. The differences between the surfaces might be explained by the friction induced temperature increase during extrusion in the die plate. The obtained results and a proposed scheme were used to explain the influence of different formulation/processing parameters, such as drug particle size and milling on the drug dissolution behaviour. Small drug particles and intact extrudates are a means of minimizing the burst release.

Solid lipid extrusion of sustained release dosage forms.

The applicability of the solid lipid extrusion process as preparations method for sustained release dosage forms was investigated in this study. Two lipids with similar melting ranges but of different composition, glyceryl palmitostearate (Precirol ATO 5) and glyceryl trimyristate (Dynasan 114), and mixtures of each lipid with 50% or 75% theophylline were extruded at temperatures below their melting ranges. Extrudates were analyzed using differential scanning calorimetry, scanning electron microscopy, porosity measurements and in vitro drug dissolution studies. The possibility of processing lipids by softening instead of complete melting and without subsequent formation of low-melting, metastable polymorphs could be demonstrated. Extrudates based on formulations of glyceryl palmitostearate/theophylline (50:50) and glyceryl trimyristate/theophylline (50:50) showed sustained release properties. An influence of extrusion conditions on the matrix structure was shown for extrudates based on a mixture of glyceryl trimyristate and theophylline (50:50). Glyceryl trimyristate tended to solidify in porous structures after melting. Exceeding a material temperature of 50.5 degrees C led to porous extrudate matrices with a faster drug release. The production of novel, non porous sustained release matrices was possible at a material temperature of 49.5 degrees C. Extrudates based on glyceryl trimyristate/theophylline (50:50) only slight changes in melting enthalpy and stable drug release profiles.

Detection of secretory IgM in tears during rhino-conjunctivitis.

BACKGROUND: With various methods, secretory immunoglobulin M (sIgM) was assessed in tears of patients with rhino-conjunctivitis. METHODS: Tears were analyzed by microimmunoelectrophoresis (MIE), size-exclusion high-pressure liquid chromatography (SE-HPLC), sodium dodecyl sulphate (SDS) electrophoresis and isoelectric focusing. RESULTS: Only very small traces of serum IgM could be found in tears of healthy volunteers. MIE showed that tear sIgM is different from serum IgM. The former migrates in the direction of the anode, while serum IgM migrates to the cathode. The SDS electropherogram of a number of patients showed an additional strong band of the sIgM mu-chain of approximately 68 kDa, after rhino-conjunctivitis. SE-HPLC showed two additional peaks for these patients, at 10.97 min and at 12.94 min, which were attributed to tear sIgM. The former peak consists of a complex of four sIgM molecules. One year later the chromatograms of the former rhino-conjunctivitis patients did not show any peak of sIgM in SE-HPLC. CONCLUSIONS: Serum IgM of a molecular weight (MW) 970 kDa appears only in normal tears at very low concentrations, as a result of transudation from the serum. In contrast, sIgM is synthesized during rhino-conjunctivitis in high concentrations in the human lacrimal glands and the conjunctiva. These increased levels of tear sIgM are due to stimuli for specific protein synthesis.

Retocolite ulcerativa na crianca: relato de caso / Ulcerative colites in childhood: report of a case

Os autores relatam o caso de uma crianca de 5 anos e meio, masculino, internado no Hospital Infantil Joana de Gusmao, em Florianopolis, SC., com quadro de abdome agudo perfurativo. A laparatomia evidennciou necrose do colo transverso com perfuracao. Realizada a colectomia transversa com colostomia proximal e fistula mucosa distal. O exame histopatologico revelou ser megacolo toxico perfurado, decorrente de retocolite ulcerativa inespecifica. Permaneceu sob tratamento clinico com sulfasalazina e corticosteroides. Posteriormente, foi submetida a colectomia total com anastomose ileo anal atravez da confeccao de uma bolsa ileal em jota. Atualmente, um ano apos a cirurgia, o paciente encontra-se com desenvolvimento pondo estatural compativel com a idade.