A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME

Hypromellose is a hydrophilic polymer widely used in immediate- and modified-release oral pharmaceutical dosage forms. However, currently available grades of hypromellose are difficult, if not impossible, to process by hot melt extrusion (HME) because of their high glass transition temperature, high melt viscosity, and low degradation temperature. To overcome these challenges, a modified grade of hypromellose, AFFINISOL? HPMC HME, was recently introduced. It has a significantly lower glass transition temperature and melt viscosity as compared to other available grades of hypromellose. The objective of this paper is to assess the extrudability and performance of AFFINISOL? HPMC HME (100LV and 4M) as compared to other widely used polymers in HME, including HPMC 2910 100cP (the currently available hypromellose), Soluplus®, Kollidon® VA 64, and EUDRAGIT® E PO. Formulations containing polymer and carbamazepine (CBZ) were extruded on a co-rotating 16-mm twin-screw extruder, and the effect of temperature, screw speed, and feed rate was investigated. The performance of the solid dispersions was evaluated based on Flory–Huggins modeling and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and dissolution. All formulations extruded well except for HPMC 2910 100cP, which resulted in over-torqueing the extruder (machine overloading because the motor cannot provide efficient energy to rotate the shaft). Among the HME extrudates, only the EUDRAGIT® E PO formulation was crystalline as confirmed by DSC, XRD, and Raman, which agreed with predictions from Flory–Huggins modeling. Dissolution testing was conducted under both sink and non-sink conditions. Sink dissolution testing in neutral media revealed that amorphous CBZ in the HME extrudates completely dissolved within 15 min, which was much more rapid than the time for complete dissolution of bulk CBZ (60 min) and EUDRAGIT® E PO solid dispersion (more than 6 h). Non-sink dissolution in acidic media testing revealed that only CBZ contained in the AFFINISOL? HPMC HME, and EUDRAGIT® E PO solid dispersions rapidly supersaturated after 15 min, reaching a twofold drug concentration compared to the CBZ equilibrium solubility. In summary, AFFINISOL? HPMC HME 100LV and AFFINISOL? HPMC HME 4M are useful in the pharmaceutical HME process to increase wetting and dissolution properties of poorly water-soluble drugs like CBZ.     

Combining Attractants and Larvicides in Biodegradable Matrices for Sustainable Mosquito Vector Control

BackgroundThere is a global need for cost-effective and environmentally friendly tools for control of mosquitoes and mosquito-borne diseases. One potential way to achieve this is to combine already available tools to gain synergistic effects to reduce vector mosquito populations. Another possible way to improve mosquito control is to extend the active period of a given control agent, enabling less frequent applications and consequently, more efficient and longer lasting vector population suppression.Conclusions/significanceCollectively, our data demonstrate the potential for the effective use of wax emulsions as slow release matrices for mosquito attractants and control agents. The results indicate that the combination of an oviposition attractant with larvicides could synergize the control of mosquito disease vectors, specifically Cx. quinquefasciatus, a nuisance pest and circumtropical vector of lymphatic filariasis and encephalitis.     

Capillary zone electrophoresis of insulin and growth hormone

The separation power of capillary zone electrophoresis was examined using highly purified and well-characterized biosynthetic human insulin, growth hormone, their derivatives, and related proteins. Mixtures of proteins were chosen to illustrate practical applications of this technique. Proteins differing slightly in structure, but equivalent in net charge, were not completely separated. Degradation of insulin by dilute acid treatment was followed by capillary zone electrophoresis, native polyacrylamide gel electrophoresis, and reversed-phase liquid chromatography. Excellent correlation was observed between these techniques. Simple equipment requirements and analysis times on the order of 10 min make capillary zone electrophoresis attractive for analytical protein separations.     

Aborjinia corallicola sp. n., a new nematode species (Nematoda: Marimermithidae) associated with the bamboo coral Acanella arbuscula (Johnson)

Systematic Parasitology - A new species of Aborjinia Özdikmen, 2010 is described from the tissues of the cold-water bamboo coral Acanella arbuscula (Johnson) from the northwest Atlantic....     

Attempts to immunise rats and mice against infection with fasciola hepatica using antigens prepared from taenia hydatigena.

Attempts were made to immunise rats and mice against infection with F. hepatica by oral dosing with T. hydatigena eggs, or by vaccination with various T. hydatigena antigen preparations. These antigens included extracts from T. hydatigena cysticerci and cyst fluid, and antigens collected during short-term (48 h) and long-term (14 days) in vitro cultivation of larvae. Immunity was assessed by the numbers of F. hepatica recovered from the challenge infection in rats, and the mortality rates of infected mice. None of the immunisation regimes with T. hydatigena antigens induced consistent, significant immunity. This was in contrast to the high level of immunity shown by rats dosed orally with F. hepatica metacercariae four weeks prior to challenge infection.     

Molecular mechanisms of memory formation

Studies with neonate chicks, trained on a passive avoidance task, suggest that at least two shorter-term memory stages precede long-term, protein synthesis-dependent memory consolidation. Posttetanic neuronal hyperpolarization arising from two distinct mechanisms is postulated to underlie formation of these two early memory stages. Maintenance of the second of these stages may involve a prolonged period of hyperpolarization brought about by phosphorylation of particular proteins. A triggering mechanism for long-term consolidation is postulated to occur at a specific time during the second stage, and may involve reinforcement-contingent release of neuronal noradrenaline stimulating cAMP-dependent intracellular processes. The possibility that astroglia may have a critical role to play in these early stages of memory processing is raised.     

Effects of Selective Alkylphosphorylation of Propionylcholinesterase on the Regeneration of Acetylcholinesterase in the Aqueous Soluble Fraction of Superior Cervical Ganglia of the Rat Following Sarin

Abstract: The rates of regeneration of acetylcholinesterase (AChE) and propionylcholinesterase (PrChE) in the supernatants of aqueous homogenates of rat superior cervical ganglia, centrifuged at 100,000 g for 90 min, were determined at 1,3, 6, and 16 h following their inactivation (>90%) by administration of sarin, 2.0μmol/kg i.v. Values were compared with those in animals in which the PrChE was continually suppressed by the repeated, fractional administration of iso-OMPA, in a total dose of 10 or 20 μmol/kg i.p. These doses of iso-OMPA alone produced 96–99% inactivation of PrChE with no detectable effect on AChE. Significant suppression of AChE regeneration by iso-OMPA administration was noted only at 6 h; in contrast with earlier findings in the cat, administration of iso-OMPA alone caused no significant increase in ganglionic AChE activity.