Solid Dispersion Controlled Release: Effect of Particle Size, Compression Force and Temperature

Solid dispersions are dynamic systems, a careful control of processing variables is required to produce desired physicochemical properties of these systems.

The influence of drug particle size, dispersion temperature and compression force on the release rate of theophylline from solid dispersed system tablets was studied. Theophylline base (micronized and granulate) were embedded into a polymeric mixture of PEG and acrylic/methacrylic esters at controlled temperature and shock cooled. Tablets were made at two compressional forces and drug release was measured spectrophotometrically over a period of fifteen hours.

The release rate of drug dispersed in these insoluble matrices was independent of particle size but not of hardness.

However, variations in ratios of polymeric mixture and dispersion temperature controls the drug release rate from inert matrix more effectively than such factors as drug particle size and lower range of tablet hardness. The fast cooling produced excellent reproducibility of drug content throughout the entire entrapment product. X-ray diffraction study demonstrated no changes in crystalline form of theophylline.     

Optical properties of Si-Si1−xGex and Si-Ge nanostructures

This paper reviews the current research status on the optical properties of Si-Si_1–xGe_x and Si-Ge nanostructures. Although this is a relatively new field, existing research has already achieved promising results in terms of both physics and possible device applications including the effect of process-induced strain in nanostructures, quantum confinement and improved optical efficiency of collective excitation in wires with reduced dimension, and especially the huge improvement of optical efficiency in quantum dots after nanofabrication. These results potentially open a new field of research into both the physics of Si-Si_1–xGe_x nanostructures and the possible applications of them in cheap Si based optoelectronic industry.     

The imidazoline I1 receptor agonist, moxonidine, inhibits insulin secretion from isolated rat islets of Langerhans

In order to study the pharmacology of the putative imidazoline receptor involved in stimulation of insulin secretion, the potent and selective imidazoline I1 receptor agonist, moxonidine, was employed. Surprisingly, this agent caused a rapid and complete inhibition of glucose-induced insulin secretion in isolated rat islets of Langerhans. This response was reversible upon removal of the compound but was only partially attenuated under conditions of complete alpha 2 blockade, suggesting that it did not derive entirely from the weak alpha 2-adrenoceptor agonist activity of moxonidine. Furthermore, the response could not be attributed to activation of imidazoline I1 receptors since it was not reproduced by a second potent imidazoline I1 receptor agonist, cimetidine, and could not be alleviated by the imidazoline I1 receptor antagonist efaroxan. The results confirm that the imidazoline receptor involved in control of insulin secretion differs from the I1 subclass and suggest that moxonidine inhibits insulin secretion by a mechanism unrelated to imidazoline I1 receptor agonism.     

Sex differences in insulin levels in older adults and the effect of body size, estrogen replacement therapy, and glucose tolerance status. The Rancho Bernardo Study, 1984-1987

OBJECTIVE--To determine if insulin levels vary with sex, independent of estrogen replacement therapy (ERT), differences in body mass index (BMI), waist-to-hip ratio (WHR), and glycemia. RESEARCH DESIGN AND METHODS--In a population-based study of older adults, insulin levels were measured before and after a standardized oral glucose tolerance test in 673 men and 849 women, all free of known diabetes. RESULTS--Age-adjusted fasting insulin levels were highest in men, intermediate in women not taking estrogen, and lowest in estrogen-treated women (P < 0.01). Differences between men and women not taking estrogen disappeared after adjusting for age and BMI, but not glycemia; estrogen-treated women had significantly lower fasting insulin levels than did men (P < 0.01) and women not taking estrogen (P < 0.01). The association of estrogen use with lower fasting insulin levels persisted after adjusting for age and WHR (P < 0.001) and was stronger among women with abnormal glucose tolerance. Age-adjusted postchallenge insulin levels were higher in women than in men (P < 0.01). The sex difference persisted after adjusting for age and BMI or glycemia. Postchallenge insulin levels did not vary by ERT. CONCLUSIONS--Men have higher fasting insulin levels than do women, whether or not the women are using ERT. Differences between men and untreated women are explained by differences in BMI, but estrogen users have lower fasting insulin levels independent of BMI. Postchallenge insulin levels are higher in women than men and are independent of ERT, BMI, and glycemia. Clinical trials in women are needed to determine whether ERT can improve insulin and glucose metabolism.     

Electrical determination of bandgap narrowing in bipolartransistors with epitaxial Si, epitaxial Si1-xGex,and ion implanted bases

The apparent bandgap narrowing in bipolar transistors with epitaxial Si, epitaxial SiGe and ion implanted bases is measured from the temperature dependence of the collector current density J_c(T). A graph of InJ_c(T)/J_o(T) as a function of reciprocal temperature is plotted, and the apparent bandgap narrowing obtained from the slope. For epitaxial base transistors, in which the boron base profiles are abrupt, a linear J_c(T)/J _o(T) characteristic is obtained, which allows the unambiguous determination of the apparent bandgap narrowing. The measured values for epitaxial Si bases are in good agreement with the theoretical model of Klaassen over a range of base doping concentrations. For Si_0.88 Ge_0.12 and Si_0.87Ge_0.13 epitaxial base heterojunction bipolar transistors (HBT's), values of bandgap narrowing of 119 and 121 meV are obtained due to the presence of the Ge, which can be compared with theoretical values of 111 and 118 meV. For the implanted base transistor, the J_c(T)/J_o(T) characteristic is not linear, and its slope is larger at high temperatures than at low. This behaviour is explained by the presence of a tail on the ion implanted profile, which dominates the Gummel number of the transistor at low temperatures     

Proteolytic release of membrane proteins: studies on a membrane-protein-solubilizing activity in CHO cells

Diverse membrane proteins are solubilized by a specific proteolytic cleavage in the stalk sequence adjacent to the membrane anchor, with release of the extracellular domain. Examples are the amyloid precursor protein, membrane-bound growth factors and angiotensin-converting enzyme (ACE). The identities and characteristics of the responsible proteases remain elusive. We have studied this process in Chinese hamster ovary (CHO) cells stably expressing wild-type ACE (WT-ACE) or juxtamembrane (stalk) deletion or chimaera mutants. Determination of the C termini (i.e. the cleavage sites) of released, soluble wild-type and mutant ACE by MALDI-TOF mass spectrometry indicated that the membrane-protein-solubilizing protease (MPSP) in CHO cells is not constrained by a particular cleavage site motif or by a specific distance from the membrane, but instead may position itself with respect to the putative proximal, folded extracellular domain adjacent to the stalk. Nevertheless, kinetic analyses of release rates indicated that a minimum distance from the membrane must be preserved. Interestingly, soluble full-length (anchor-plus) WT-ACE incubated with fractions of, or intact, CHO cells was not cleaved. In all cases, release was stimulated by a media change or by the addition of phorbol ester, with rate enhancements of 5- and 50-fold, respectively, for WT-ACE. The phorbol ester effect was abolished by staurosporine, a protein kinase C (PKC) inhibitor. We propose that the CHO cell MPSP that solubilizes ACE: (1) only cleaves proteins embedded in a membrane; (2) requires an accessible stalk and cleaves at a minimum distance from both the membrane and proximal extracellular domain; (3) positions itself primarily with respect to the proximal extracellular domain and (4) is regulated in part by a PKC-dependent mechanism.     

Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes

We and others have previously demonstrated that human alveolar macrophages produce more PGE2 in response to lipopolysaccharide (LPS) than do blood monocytes. We hypothesized that this observation was due to a greater increase in prostaglandin H synthase-2 (PGHS-2) enzyme mass in the macrophage compared to the monocyte. To evaluate this hypothesis, alveolar macrophages and blood monocytes were obtained from healthy nonsmoking volunteers. The cells were cultured in the presence of 0 to 10 micrograms/ml LPS. LPS induced the synthesis of large amounts of a new 75-kD protein in human alveolar macrophages, and a lesser amount in monocytes. Synthesis of this protein required more than 6 h and peaked in 24 to 48 h; the protein reacted with an anti-PGHS-2 antibody prepared against mouse PGHS-2. Associated with synthesis of the protein was a marked increase in LPS-stimulated and arachidonic acid-stimulated synthesis of PGE2 by alveolar macrophages compared to monocytes. Cells not exposed to LPS contained only PGHS-1 and synthesized very little PGE2 during culture or in response to exogenous arachidonic acid. An LPS-induced mRNA, which hybridized to a human cDNA probe for PGHS-2 mRNA, was produced in parallel with production of this new protein and was produced in much greater amounts by alveolar macrophages compared to blood monocytes. This mRNA was not detectable in cells not exposed to LPS. In contrast, both types of cells contain mRNA, which hybridizes to a cDNA probe for PGHS-1. This mRNA did not increase in response to LPS. LPS also had no effect on PGHS-1 protein. These data demonstrate that PGE2 synthesis in human alveolar macrophages and blood monocytes correlates to the mass of PGHS-2 in the cell. We conclude that the greater ability of the macrophage to synthesize PGE2 in response to LPS is due to greater synthesis of PGHS-2 by the macrophage.