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January/February 2010

Volume 13, Issue 1

 

 

 

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Articles in this Issue

  • Drug Solubilization Strategies Applying Nanoparticulate Formulation and Solid Dispersion Approaches...

    Carsten TImpe, Ph.D.
    Over the last decade, a large number of publications and pharmaceutical conferences dealt with drug delivery strategies for an increasing number of poorly water soluble and lipophilic drugs. To deliver these appropriately, typically it requires application of non-standard formulation technologies (apart from salt formation and micronization), e.g. lipid/surfactant based SEDDS/SMEDDS (self-emulsifying/self-microemulsifying) or solid dispersion formulation approaches. Most recently many molecules cannot be well delivered even when they are formulated with these tools due to low solubility in lipidic and polymeric excipients.
  • Ultra Fast Liquid Chromatography- MS/MS for Pharmacokinetic and Metabolic Profiling Within...

    Sam Wainhaus Ph.D., Cymbelene Nardo, Ryan Anstatt, Shiyong Wang, Kimberly Dunn-Meynell, Walter Korfmacher, Ph.D.
    The primary task within drug discovery in the pharmaceutical industry is to bring forth compounds that have the best overall profile. This insures the highest chance for success within drug development where new chemical entities fail for reasons, such as toxicity, lack of efficacy and poor human pharmacokinetics.
  • Salt and Polymorph Selection Strategy Based on the Biopharmaceutical Classification System...

    M. Sherry Ku
    The Biopharmaceutics Classification System [1,2] (BCS) is not only a useful tool for obtaining waivers for in-vivo bioequivalence studies but also for decision making in the discovery and early development of new drugs. It is because BCS is based on a scientific framework to classify drugs using solubility and permeability as the rate limiting steps in oral absorption.
  • Pharmaceutical Surveillance with Rapid Spectroscopic Screening Technologies

    John Kauffman, Ph.D., Connie M. Gryniewicz-Ruzicka, Ph.D., Sergey Arzhantsev, Ph.D., Jamie D. Dunn, Ph.D., John A. Spencer, Ph.D., Steven Wolfgang, Ph.D., Xiang Li, Lindsey N. Pelster, Benjamin J. Westenberger, Dr. Lucinda F. Buhse, Ph.D.
    The number of drugs imported into the US has more than doubled in the past decade [1], and globalization of the pharmaceutical supply chain appears to be increasing the risk that American pharmaceutical consumers will be exposed to drug products that have been contaminated, counterfeited or mislabeled [2].
  • A Systematic Method Development Strategy for Water Determinations in Drug Substance Using Karl...

    Leon Zhou, Ph.D., Jerome M. Socha, Frederick G. Vogt, Ph.D., Sarah Chen, Ph.D., Alireza S. Kord, Ph.D.
    Karl Fischer titration (KFT) is the most widely used analytical technique for determination of water content in the pharmaceutical industry. Accurate determination of water content is not only important in understanding the performance of drug substances and drug products, but also a limiting factor to the accuracy of drug content calculated on anhydrous and solvent free basis.
  • Revision of PDA Technical Report Number 33

    Michael J. Miller, Ph.D., Jeanne Moldenhauer
    PDA Technical Report Number 33 (TR33), Evaluation, Validation and Implementation of New Microbiological Testing Methods, was originally published in 2000 and was the first guidance document for how to select, validate and implement alternative and rapid microbiological methods (RMM). The document quickly became the gold standard for RMM validation strategies and has been used to successfully qualify new microbiology technologies within the U.S. and Europe.
  • Lyophilization Strategies for Development of a High-Concentration Monoclonal Antibody Formulation:...

    Akhilesh Bhambhani, Ph.D., Jeffrey T. Blue
    Development of a successful subcutaneous antibody therapy requiring chronic administration at high dosing (several mg/kg), particularly when coupled with prefilled syringe and autoinjector device for at-home administration, is dependent on the development of a stable formulation at high concentration. This is very challenging due to a few key factors. First is the current limitation on subcutaneous injection volume (=1.5 ml), and more importantly due to limited intrinsic stability in a highly concentrated aqueous solution.
  • Single-Use Technology and Its Carbon and Water Footprints, Part 2: “Bioreactors - To Be Or...

    Lindsay Leveen
    In preparing this article that will discuss the future role of single use (disposable) bio reactors, I was somewhat perplexed by the more fundamental question of whether the biopharmaceutical industry really needs any increased manufacturing capacity, or is there simply such a glut of traditional manufacturing capacity that only a very small amount of additional capacity will be added in the foreseeable future?
  • Monitoring of Blending Uniformity Form Conversion and Fluid Bed Drying by Near Infrared and...

    Claudia C. Corredor, Ph.D., Dimuthu Jayawickrama, PhD, Gary McGeorge, Ph.D, Douglas Both
    Since the publication of the Food and Drug Administration (FDA) Process Analytical Technology (PAT) guideline: A framework for innovative development, Manufacturing, and Quality Assurance [1], pharmaceutical companies have undertaken efforts to improve product quality through increased process understanding and in-process controls rather than solely relying on end-product testing [2,3].
  • Risk and Scientific Considerations in the Environmental Monitoring of Isolators in Aseptic...

    James Akers, Ph.D.
    Isolator technology for aseptic manufacturing was introduced in Europe over 20 years ago. Since that introduction, isolators have become a widely accepted environmental control system for aseptic processing. Certainly, isolators have run into a certain amount of turbulence in their trajectory to a well-accepted technological solution in 2010. The purpose of this communication is not to revisit the well-known story of Isolator technology in aseptic manufacturing, but rather to consider what we have learned over these two decades and to suggest how we might most productively and safely apply these lessons.
  • Dissolution Testing of Solid Products

    Rolf Brickl, Ph.D.
    Standard dissolution testing employs sink conditions and thus is not predictive for absorbability of poorly soluble drugs in vivo. Therefore special dissolution tests for optimization of formulations were developed: most suitable is to dissolve the highest assumed dose in man in a volume of 250 ml at the pH of minimal solubility in the range of pH 1 – 6 using low buffer strengths. Furthermore a test system for extended release of poorly soluble drugs using octanol as absorption phase was developed.
  • Functionality and Performance of Excipients in Quality-by-Design World, Part VII: Quality Risk...

    Dr. Chris Moreton, Ph.D.
    Quality by Design (QbD) is a means of developing more robust formulations that will benefit the patient because the quality risks are minimized. Quality Risk Management complements QbD and helps to identify risks and weaknesses associated with systems, development projects and products.
  • Potential Mycoplasma Contaminants: Inactivation during Production of Inactivated Egg-Based...

    Dmitriy V. Volokhov, DVM, Ph.D., DACVM, Donna K. F. Chandler, Ph.D., Vladimir E. Chizhikov, Ph.D.
    Mycoplasmas (the trivial name for Mollicutes) comprise the class of broadly distributed, wall less free living bacteria with one of the smallest known genomes supporting bacterial self replication [1]. While many mycoplasmas are commensals colonizing a wide range of plant, insect, reptilian, avian, mammalian, and human hosts, a number of mycoplasma species are pathogenic and cause disease in their natural hosts.
  • Monitoring GMP Compliance in an Analytical R&D Laboratory by use of a Peer-Led Program

    Peter Tattersall, Ph.D., Michelle Kubin, Anwar Hussain
    During pharmaceutical development, the performance of pharmaceutical products intended for investigational purposes are often unknown and/or not optimized, however, one element critical to the safety and efficacy of investigational medicines is compliance with the cGMPs. Several mechanisms can be used to enhance and enable compliance in analytical laboratories where investigational medicines are tested and released for clinical use.
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