Equilibrium binding interactions between lotrafilcon a soft contact lenses and the two prostaglandin antiglaucoma drugs bimatoprost and tafluprost.

Objectives: To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions.

Methods: Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution.

Formoterol fumarate and roxithromycin effects on muscle mass in an animal model of cancer cachexia.

Our study probed the effects of the beta-2 adrenergic agonist, formoterol and the macrolide antibiotic, roxithromycin, on muscle wasting in a well-characterized animal model of cancer cachexia. Female Wistar rats were inoculated with Yoshida AH130 ascites hepatoma (AH) cells to induce rapid and severe cachexia as demonstrated by wet weight determinations of the hearts, gastrocnemius muscles and carcasses. The control animals received saline (vehicle) inoculations.

Orthogonal HPLC methods for quantitating related substances and degradation products of pramlintide.

Pramlintide is a 37-amino acid peptide that is being evaluated as a drug candidate for treating people with type 1 and insulin-using type 2 diabetes. Two high-performance liquid chromatography (HPLC) methods were developed for quantitating related substance impurities in pramlintide drug substance as well as degradation products of pramlintide formulated for parenteral administration. The methods differ with respect to separation mode and therefore provide orthogonal information concerning related substances and degradation products.

Pramlintide injection drug product robustness studies.

The article examines the effects of temperature excursions and actual dose withdrawal on the quality of pramlintide injection, a multidose liquid parenteral formulation. Studies were designed to demonstrate product robustness under conditions that may occur during patient use. Pramlintide %Purity was determined by two high-performance liquid chromatography (HPLC) methods, a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method.

Kinetics of pramlintide degradation in aqueous solution as a function of temperature and pH.

The stability of the 37-amino acid peptide pramlintide, in aqueous solution, was studied as a function of pH and temperature. Samples of pramlintide formulated as a parenteral product were exposed to elevated temperatures and to realistic storage conditions for as long as 30 months. Pramlintide degradation was monitored by three high-performance liquid chromatography (HPLC) methods: a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method for percentage purity determination by area normalization, plus a second RP-HPLC method for potency determination versus external standards.

Fitness Landscapes and the Precautionary Principle: The Geometry of Environmental Risk.

/ A generalized mathematical model for exploring the implications of the Precautionary Principle is developed. This model draws on recent developments in the field of complex adaptive systems theory. The existence and importance of the Precautionary Principle in the field of environmental law is taken as given and used as justification for the development of models for exploring the principle's implications.

Efficacy of Heat Disinfection With the Aksys Personal Hemodialysis System.

The first objective of this study was to validate the use of water at 85°C ± 5°C to achieve high-level disinfection of a clean-in-place extracorporeal dialysis circuit. The second objective was to demonstrate that applying this hot water method to the entire fluid pathways of a newly designed dialysis instrument, including an integral reverse-osmosis membrane, routinely allowed the production of back-filtered dialysate meeting the U.S.

Tearing down the barriers to daily home hemodialysis and achieving the highest value renal therapy through holistic product design.

Renal therapy value can be defined as the ratio of outcomes achieved by a dialytic therapy to the total cost of providing that therapy. One desirable goal of any dialysis modality would be the achievement of maximum value. Unfortunately, with conventional hemodialysis and peritoneal dialysis modalities, improving outcomes has always been linked to a simultaneous increase in costs, thereby leaving value relatively unchanged.

Gamma irradiation effects on molecular weight and in vitro degradation of poly(D,L-lactide-CO-glycolide) microparticles.

Purpose: The objective of the reported work was to quantitatively establish gamma-irradiation dose effects on initial molecular weight distributions and in vitro degradation rates of a candidate erodible biopolymeric delivery system.

Methods: Poly(D,L-lactide-coglycolide) (PLGA) porous microparticles were prepared by a phase-separation technique using a 50:50 copolymer with 30,000 nominal molecular weight. The microparticles were subjected to 0, 1.

Osseous regeneration in the rat calvarium using novel delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2).

In the current investigation, we report osseous regeneration in critical-size rat calvarial defects using recombinant human bone morphogenetic protein-2 (rhBMP-2) and novel delivery systems based on biomaterials. The novel systems combine rhBMP-2 with dry powder microparticles of poly(D,L-lactide-co-glycolide) (PLGA). The mixture of rhBMP-2 with PLGA microparticles is added to an aqueous solution of biopolymer to yield a semisolid paste.

Acid-catalyzed peptide bond hydrolysis of recombinant human interleukin 11.

Recombinant human interleukin 11 (rhIL-11) is a multispectrum cytokine that plays an important role in megakaryocytopoiesis and platelet production. Probing rhIL-11 chemical reactivity in aqueous solution is an important initial step in developing a dosage form for rhIL-11 clinical trials. This report documents rhIL-11 degradation kinetics at 50 degrees C in solutions adjusted to pH 3.

Biotechnology and bone graft substitutes.

Trauma, disease, developmental deformities, and tumor resection frequently cause bone defects that seriously challenge the skills of orthopedic and maxillofacial surgeons. Currently, repairing osseous deficiencies involves various medical surgical techniques, including autogenous grafts, allografts, internal and external fixation devices, electrical stimulation, and alloplastic implants. The existing technology, though effective in many cases, still is beset with numerous difficulties and disadvantages.

Degradation pathways for recombinant human macrophage colony-stimulating factor in aqueous solution.

Recombinant human macrophage colony-stimulating factor (rhM-CSF) promotes macrophage proliferation and activity. rhM-CSF clinical trials are currently in progress and require a stable, pharmaceutically acceptable dosage form. This report documents pH effects on rhM-CSF degradation profiles in aqueous solution, with an emphasis on identifying degradation products.

Eliminating interferences in a compendial test for oxidizable substances in water.

The United States Pharmacopoeia (USP) uses acidified potassium permanganate to test for dissolved organics in pharmaceutical-grade water. In the test, a standard permanganate concentration is added to a boiling, acidified water sample. Visually inspecting the sample for residual permanganate determines whether the sample passes (pink color remains) or fails (pink color disappears) the test.

Influence of solute degradation on the accumulation of solutes migrating into solution from polymeric parenteral containers.

Solute stability in solution, in addition to solute-polymer interaction properties and the total solute available pool, impacts the interaction between a polymeric container and a parenteral product, specifically in terms of the migration of trace polymer components into the contained solution. A specific solute/polymer system has been studied with respect to properties impacting the magnitude and rate of solute migration from the polymer into solution. The solute, an alkyl ester, originates in a polyolefin composite packaging material.

Determination of solute-polymer interaction properties and their application to parenteral product container compatibility evaluations.

Kinetic and thermodynamic interaction properties between dialkyl phthalate test compounds and a polyolefin polymer were examined via a permeation-cell experimental design. Disappearance and appearance rates of solute in the receptor and donor solutions, as well as the equilibrium composition of the test system, are used to determine sorption and diffusion coefficients and the solute/polymer equilibrium binding constant. Sorption rate constants and diffusion coefficients exhibit Arrenhius-type behavior.

Electrochemical evaluation of the interaction between ascorbic acid and the cardiotonic drug RS-82856.

The solution phase interaction between ascorbic acid and the cardiotonic drug N-cyclohexyl-N-methyl-4(7-oxy 1,2,3,5-tetrahydroimidazol[2,1-b] quinazolin-2-one butyramide (RS-82856) was evaluated using a differential pulse voltammetric technique. Shifts in the peak potential of ascorbic acid to higher energy as well as decreases in peak current values were monitored as a function of RS-82856 concentration. The electrochemical data were obtained under conditions where both the drug and the ascorbic acid concentrations exhibited linear relationships with peak current values.

Temperature and pH dependence of fluocinolone acetonide degradation in a topical cream formulation.

We investigated the degradation of fluocinolone acetonide (FA) incorporated into an oil-in-water cream base. The study examined the influence of temperature (23 to 80 degrees C) and cream pH (pH 2.3 to 6) on FA degradation rates.

Nonquaternary cholinesterase reactivators. 3. 3(5)-Substituted 1,2,4-oxadiazol-5(3)-aldoximes and 1,2,4-oxadiazole-5(3)-thiocarbohydroximates as reactivators of organophosphonate-inhibited eel and human acetylcholinesterase in vitro.

As an extension of an earlier investigation (J. Med. Chem.

Stability of ganciclovir sodium (DHPG sodium) in 5% dextrose or 0.9% sodium chloride injections.

The stability of 9-[(1,3-dihydroxy-2-propoxymethyl]) guanine sodium (ganciclovir sodium, also known as DHPG sodium) in two infusion solutions was studied. Lyophilized ganciclovir sodium 500 mg was reconstituted with sterile water 10 mL to give a theoretical concentration of 50 mg/mL. After reconstitution, 6-mL aliquots of the solution were added to 100 mL of 0.

Multidimensional column-switching liquid chromatographic method for dissolution testing of enprostil soft elastic gelatin capsules.

Enprostil (methyl 7-[(1 R,2R,3R)-3-hydroxy-2-[(E)-(3R)-3-hydroxy-4- phenoxy-1-butenyl]-5-oxocyclopentyl]-4,5-heptadienoate), an E-type prostaglandin exhibiting anti-ulcer activity, is formulated as a propylene carbonate solution filled into soft elastic gelatin (SEG) capsules. Enprostil SEG capsules were maintained for timed intervals at 50 degrees C, 30 degrees C, and room temperature, and the quantity of drug released upon complete capsule dissolution was determined as a function of storage condition. The dissolution test adhered to USP XXI guidelines (paddle method) and used a multidimensional HPLC technique to provide a sensitive and selective enprostil assay.