Marcus E. Brewster

Janssen Research & Development, LLC, Raritan, New Jersey, United States

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Publications (254)807.38 Total impact

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    ABSTRACT: Application of amorphous solid dispersions (ASDs) is considered one of the most promising approaches to increase the dissolution rate and extent of bioavailability of poorly water soluble drugs. Such intervention is often required for new drug candidates in that enablement, bioavailability is not sufficient to generate a useful product. Importantly, tableting of ASDs is often complicated by a number of pharmaceutical and technological challenges including poor flowability and compressibility of the powders, compression-induced phase changes or phase separation and slow disintegration due to the formation of a gelling polymer network (GPN). The design principles of an ASD-based system include its ability to generate supersaturated systems of the drug of interest during dissolution. These metastable solutions can be prone to precipitation and crystallization reducing the biopharmaceutical performance of the dosage form. The main aim of the research in this area is to maintain the supersaturated state and optimally enhance bioavailability, meaning that crystallization should be delayed or inhibited during dissolution, as well as in solid phase (e.g., during manufacturing and storage). Based on the expanding use of ASD technology as well as their downstream processing, there is an acute need to summarize the results achieved to this point to better understand progress and future risks. The aim of this review is to focus on the conversion of ASDs into tablets highlighting results from various viewpoints. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Pharmaceutics 03/2015; 486(1-2). DOI:10.1016/j.ijpharm.2015.03.053 · 3.79 Impact Factor
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    ABSTRACT: High speed electrospinning (HSES), compatible with pharmaceutical industry, was used to demonstrate the viability of the preparation of drug-loaded polymer nanofibers with radically higher productivity than the known single-needle electrospinning (SNES) setup. Poorly water-soluble itraconazole (ITRA) was formulated with PVPVA64 matrix polymer using four different solvent-based methods such as HSES, SNES, spray drying (SD) and film casting (FC). The formulations were assessed in terms of improvement in the dissolution rate of ITRA (using a "tapped basket" dissolution configuration) and analysed by SEM, DSC and XRPD. Despite the significantly increased productivity of HSES, the obtained morphology was very similar to the SNES nanofibrous material. ITRA transformed into an amorphous form, according to the DSC and XRPD results, in most cases except the FC samples. The limited dissolution of crystalline ITRA could be highly improved: fast dissolution occurred (>90% within 10min) in the cases of both (the scaled-up and the single-needle) types of electrospun fibers, while the improvement in the dissolution rate of the spray-dried microspheres was significantly lower. Production of amorphous solid dispersions (ASDs) with the HSES system proved to be flexibly scalable and easy to integrate into a continuous pharmaceutical manufacturing line, which opens new routes for the development of industrially relevant nanopharmaceuticals. Copyright © 2015. Published by Elsevier B.V.
    International Journal of Pharmaceutics 01/2015; 480(1-2). DOI:10.1016/j.ijpharm.2015.01.025 · 3.79 Impact Factor
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    ABSTRACT: We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG750-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC0-∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy.
    European Journal of Pharmaceutics and Biopharmaceutics 05/2014; DOI:10.1016/j.ejpb.2014.05.014 · 4.25 Impact Factor
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    ABSTRACT: This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as imaging methods, perfusion models, models for predicting segmental/regional absorption, in vitro in vivo correlations as well as models to investigate the effects of excipients and the role of food on drug absorption. One goal of the authors was to clearly identify the gaps in todays knowledge in order to stimulate further work on refining the existing in vivo models and demonstrate their usefulness in drug formulation and product performance testing.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 03/2014; 57. DOI:10.1016/j.ejps.2014.02.010 · 3.01 Impact Factor
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    ABSTRACT: Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silico and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will when successful provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2013; 57. DOI:10.1016/j.ejps.2013.10.015 · 3.01 Impact Factor
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    ABSTRACT: OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organisation, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in our knowledge of gastrointestinal (GI) drug absorption and deliver a framework for rational application of predictive biopharmaceutics tools for oral drug delivery and. This will be achieved through novel prospective investigations to define new methodologies as well as refinement of existing tools. Extensive validation of novel and existing biopharmaceutics tools will be performed using API, formulations and supporting datasets from industry partners. A combination of high quality in vitro or in silico characterizations of API and formulations will be integrated into physiologically based in silico biopharmaceutics models capturing the full complexity of GI drug absorption. This approach gives an unparalleled opportunity to initiate a transformational change in industrial research and development to achieve model-based pharmaceutical product development in accordance with the Quality by Design concept. Benefits include an accelerated and more efficient drug candidate selection, formulation development process, particularly for challenging projects such as low solubility molecules (BCS II and IV), enhanced and) and modified-release formulations, as well as allowing optimisation of clinical product performance for patient benefit. In addition, the tools emerging from OrBiTo is expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 11/2013; 57. DOI:10.1016/j.ejps.2013.10.012 · 3.01 Impact Factor
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    ABSTRACT: Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection with in vivo biopharmaceutical performance has often been ignored. More recently, the switch to assessing drug products in a more biorelevant and mechanistic manner has advanced the understanding of drug formulation behavior. Notwithstanding this evolution, predicting the in vivo biopharmaceutical performance of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro tools. Development and optimizing innovative, predictive Oral Biopharmaceutical Tools is the main target of the OrBiTo project within the Innovative Medicines Initiative (IMI) framework. A combination of physico-chemical measurements, in vitro tests, in vivo methods, and physiology-based pharmacokinetic modeling is expected to create a unique knowledge platform, enabling the bottlenecks in drug development to be removed and the whole process of drug development to become more efficient.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2013; 57. DOI:10.1016/j.ejps.2013.08.024 · 3.01 Impact Factor
  • Thorsteinn Loftsson, Marcus E. Brewster
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    ABSTRACT: Cyclodextrins are value-adding functions excipients which have garnered significant interest and are widely used in pharmaceutical and nutraceutical products. These materials can contribute to the optimal biopharmaceutical performance of a medicine and in some cases are enabling, meaning that the drug product would not be possible without the technology. It has been estimated that products enabled by chemically modified cyclodextrins account for sales of almost US$2 billion (2008 figures). While all compounds will not necessarily benefit from the application of cyclodextrins, the approach is simple to test. Based on this simplicity as well as the low toxicological potential of these materials, cyclodextrins are often used in early drug screening and early clinical assessments and figure highly in formulation decision trees. While solubilization is, to date, the most often cited reason for using cyclodextrins, their ability to influence stability as well as other aspects of a drug suggests a significant potential for the derivatives in the future. Thus, assessments of cyclodextrin complexation and aggregation point to the possibility of increased delivery through biological membranes as well as drug products with improved shelf-lives. Cyclodextrins have also gained interest as components of siRNA delivery vectors as well as in numerous industrial applications.
    Drug Delivery Strategies for Poorly Water-Soluble Drugs, 02/2013: pages 67-101; , ISBN: 9780470711972
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    ABSTRACT: Supersaturating Drug Delivery Systems (SDDS) hold the promise of enabling intestinal absorption for difficult-to-formulate, poorly soluble drug candidates based on a design approach that includes (1) converting the drug into a high energy or rapidly dissolving system which presents a supersaturated solution to the gastrointestinal environment and (2) dosage form components that act to stabilize the formed metastable drug solution through nucleation and/or crystal growth inhibition. The appropriate development and study of SDDS require that useful and biorelevant supersaturation and precipitation assays are available. This review summarizes different methodological aspects of currently available in vitro assays, including the generation of supersaturation (solvent shift, pH shift or formulation-induced), the quantification of supersaturation and the detection of precipitation. Also down-scaled approaches, including 96-well plate setups, are described and situated in the pharmaceutical development cycle based on their consumption of API as well as time requirements. Subsequently, the ability to extrapolate in vitro supersaturation assessment to the in vivo situation is discussed as are direct and indirect clinical tools that can shed light on SDDS. By emphasizing multiple variables that affect the predictive power of in vitro assays (e.g. the nature of the test media, hydrodynamics, temperature and sink versus non-sink conditions), this review finally highlights the need for further harmonization and biorelevance improvement of currently available in vitro procedures for supersaturation and precipitation evaluation.
    International Journal of Pharmaceutics 11/2012; DOI:10.1016/j.ijpharm.2012.11.026 · 3.79 Impact Factor
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    ABSTRACT: Cyclodextrins have gained currency as useful solubilizing excipients with an ever increasing list of beneficial properties and functionalities. Although their use in liquid dosage forms including oral and parenteral solutions is straightforward, their application to solids can be confounded by the added bulk that is contributed to the formulation. This factor has limited the use of cyclodextrin in tablets and relates systems mainly to potent drug substances. Increasing the ability of cyclodextrins to complex with drug through a manipulation of their complexation efficiency (CE) may expand the use of these materials to the increasing list of drug candidates and marketed drugs who may benefit from this technology. This brief review assesses tools and materials that have been suggested for increasing the CE for pharmaceutically useful cyclodextrins and drugs. The relative importance of impacting the drug solubility (S 0) and phase‐solubility isotherm slope is discussed in the context of drug ionization and salt use; the impact of polymers, charge interactions, and charge shielding; and the coincidental formation of other complex types in the media. The influence of drug form as well as supersaturation is also discussed in the context of the responsible mechanisms along with aggregation, inclusion, and noninclusion complex formation. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3019–3032, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23077 · 3.01 Impact Factor
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    ABSTRACT: Deamidation of asparagine‐containing proteins and peptides results in the formation of hydrolysis products via a reactive succinimide intermediate. In amorphous lyophile formulations at low water content, nucleophilic amine groups in neighboring molecules can effectively compete with water for reaction with the succinimide intermediate resulting in the formation of a variety of covalent amide‐linked adducts. This study examines the effects of changes in percentage of a polymeric excipient [hypromellose (HPMC)] and water content on the degradants formed from a model asparaginyl peptide (Gly–Phe–l‐Asn–Gly) in amorphous solids also containing an excess of Gly–Val and carbonate buffer and stored at 40°C. Degradation of Gly–Phe–l‐Asn–Gly and formation of succinimide intermediates, aspartyl peptides, and covalent amide‐linked adducts were monitored by high‐performance liquid chromatography. In all formulations and storage conditions, the formation kinetics of aspartyl hydrolysis products and covalent adducts could be described by a mechanism‐based model that assigned a central role to the succinimide intermediate. Increasing the percentage of HPMC (i.e., reactant dilution) favored the formation of hydrolysis products over covalent amide‐linked adducts, consistent with the bimolecular nature of covalent adduct formation. Increases in water content as relative humidity (RH) was varied from 33% to 75% produced orders‐of‐magnitude increases in the rate constants for succinimide formation and hydrolysis with both becoming nearly constant at high water contents. A bell‐shaped profile for the dependence of the rate of covalent adduct formation on water content was observed, a result that may be indicative of phase separation at higher RHs. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3142–3156, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23092 · 3.01 Impact Factor
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    ABSTRACT: Methotrexate (MTX) has been used to treat rheumatoid arthritis at low doses and leukemia at high doses; however, this drug can produce severe side effects. Our hypothesis is that MTX side effects can be attenuated by directing the drug to the target cells (i.e., leukocytes) using (cyclo(1,12)PenPRGGSVLVTGC) peptide (cIBR). To test this hypothesis, MTX was conjugated to the N‐terminus of cIBR peptide to give MTX–cIBR conjugate. MTX–cIBR (5.0 mg/kg) suppressed joint arthritis in adjuvant arthritis rats and prevented periarticular inflammation and bone resorption of the limb joints. In vitro, the toxicity of MTX–cIBR peptide against Molt‐3 T cells was inhibited by anti‐lymphocyte function‐associated antigen‐1 (LFA‐1) antibody and cIBR peptide in a concentration‐dependent manner, suggesting that the uptake of MTX–cIBR was partially mediated by LFA‐1. Chemical stability studies indicated that MTX–cIBR was most stable at pH 6.0. The MTX portion of MTX–cIBR was unstable under acidic conditions, whereas the cIBR portion was unstable under basic conditions. In biological media, MTX–cIBR had short half lives in rat plasma (44 min) and homogenized rat heart tissue (38 min). This low plasma stability may contribute to the low in vivo efficacy of MTX–cIBR; therefore, there is a need to design a more stable conjugate to improve the in vivo efficacy. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3275–3291, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). · 3.01 Impact Factor
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    ABSTRACT: Human serum albumin is the most abundant protein in the blood. It is clinically used in the treatment of severe hypoalbuminemia and as a plasma expander. The use of albumins as a carrier for drugs is currently being developed, and some are now in the preclinical and clinical trial stages. The main technologies for utilizing an albumin as a drug carrier are protein fusion, polymerization and surface modification, and so on. Among these technologies, albumin dimerization has wide clinical applications as a plasma expander as well as a drug carrier. Despite the fact that many reports have appeared on drugs using an albumin dimer as a carrier, our knowledge of the characteristics of the albumin dimer itself is incomplete. In this review, we summarize the structural characteristics of recombinant albumin dimers produced by two methods, namely, chemical linkage with 1,6‐bis(maleimido)hexane and genetically linked with an amino acid linker, and the physicochemical characteristics and biological properties of these preparations. Finally, the potential for pharmaceutical applications of albumin dimers in clinical situations is discussed. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3033–3046, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23181 · 3.01 Impact Factor
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    ABSTRACT: AbstractA steady‐state mass transfer model that incorporates convection, diffusion, ionic migration, and ionization reaction processes was extended to describe the dissolution of weak acids under laminar flow and a rotating disk hydrodynamics. The model accurately predicted the experimental dissolution rates of benzoic acid, 2‐naphthoic acid, and naproxen in unbuffered and monoprotic buffers within the physiological pH range for both hydrodynamic systems. Simulations at various flow rates indicated a cube root dependency of dissolution rate on the flow rate for a given bulk pH value for the laminar hydrodynamic system, as proposed earlier by Shah and Nelson (1975. J Pharm Sci 64(9):1518–1520) for neutral compounds. The model has limitations in its ability to accurately predict the dissolution of weak acids under certain conditions that imposed steep concentration gradients, such as high pH values, and for polyprotic buffer systems that caused the numerical solution to be unstable, suggesting that alternative numerical techniques may be required to obtain a stable numerical solution at all conditions. The model presents many advantages, most notably the ability to successfully predict the complex process under physiological conditions without simplifying assumptions, and therefore accurately representing the system in a comprehensive manner. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3180–3189, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23209 · 3.01 Impact Factor
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    ABSTRACT: Interaction of colistin and colistin methanesulfonate (CMS) with liposomes has been studied with the view to understanding the limitations to the use of liposomes as a more effective delivery system for pulmonary inhalation of this important class of antibiotic. Thus, in this study, liposomes containing colistin or CMS were prepared and characterized with respect to colloidal behavior and drug encapsulation and release. Association of anionic CMS with liposomes induced negative charge on the particles. However, degradation of the CMS to form cationic colistin over time was directly correlated with charge reversal and particle aggregation. The rate of degradation of CMS was significantly more rapid when associated with the liposome bilayer than when compared with the same concentration in aqueous solution. Colistin liposomes carried positive charge and were stable. Encapsulation efficiency for colistin was approximately 50%, decreasing with increasing concentration of colistin. Colistin was rapidly released from liposomes on dilution. Although the studies indicate limited utility of colistin or CMS liposomes for long duration controlled‐release applications, colistin liposomes were highly stable and may present a potential opportunity for coformulation of colistin with a second antibiotic to colocalize the two drugs after pulmonary delivery. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3347–3359, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23203 · 3.01 Impact Factor
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    ABSTRACT: Wet milling was previously demonstrated as a simple process for producing agglomerates of budesonide nanoparticles (also known as NanoClusters) for use in dry powder aerosol formulation. The resulting budesonide NanoCluster powders exhibited a large emitted fraction and a high fine particle fraction (FPF) from a Monodose® dry powder inhaler. In this work, excipients were added premilling or postmilling and the performance of budesonide NanoCluster dry powders was investigated. Sodium chloride, Pluronic®, or ethanol was added prior to milling due to their ability to modify surface tension or ionic strength and thereby affect the attrition/agglomeration process. Lactose or l‐leucine was added after milling because these are known to modify powder flow and dispersion. The chemical stability of budesonide was maintained in all cases, but the physical aerosol properties changed substantially with the addition of excipients. In all cases, the addition of excipients led to an increase in the size of the budesonide NanoClusters and tended to reduce the emitted fraction and FPF. Titrating excipients may provide a means to discretely modify the aerosol properties of budesonide NanoClusters but did not match the performance of excipient‐free NanoCluster powder. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3434–3444, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23197 · 3.01 Impact Factor
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    ABSTRACT: Amorphous solid dispersions have great potential for enhancing oral absorption of poorly soluble drugs. Crystallization behavior during storage and after exposure to aqueous media must be examined in detail for designing stable and effective amorphous formulations, and it is significantly affected by the intrinsic properties of an amorphous drug. Many attempts have been made to correlate various thermodynamic parameters of pharmaceutical glasses with their crystallization behavior; however, variations in model drugs that could be used for such investigation has been limited because the amorphous characteristics of drugs possessing a high crystallization tendency are difficult to evaluate. In this study, high‐speed differential scanning calorimetry, which could inhibit their crystallization using high cooling rates up to 2000°C/s, was employed for assessing such drugs. The thermodynamic parameters of the glasses, including glass transition temperature (T g) and fragility, were obtained to show that their crystallization tendency cannot be explained simply by the parameters, although there have been general thought that fragility may be correlated with crystallization tendency. Also investigated was correlation between the thermodynamic parameters and crystallization tendency upon contact with water, which influences in vivo efficacy of amorphous formulations. T g was correlated well with the crystallization tendency upon contact with water. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3239–3248, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23166 · 3.01 Impact Factor
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    Journal of Pharmaceutical Sciences 09/2012; 101(9):2989-95. DOI:10.1002/jps.23179 · 3.01 Impact Factor
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    ABSTRACT: Levofloxacin is a broad‐spectrum antibiotic that exists as a hemihydrate under ambient conditions. In addition to the hemihydrate, there are three known crystalline anhydrate forms, denoted as α, β, and γ. In this study, differential scanning calorimetry (DSC), thermogravimetric analysis, Raman spectroscopy, single‐crystal and powder X‐ray diffraction, and solid‐state NMR spectroscopy were used to investigate the transitions that occurred upon dehydration to the anhydrate as well as additional transitions that occurred to the anhydrous material upon heating/cooling. An enantiotropic conversion was observed in the DSC around 54°C corresponding to the conversion of the γ form to a new form, denoted as the δ form. Raman spectroscopy, powder X‐ray diffraction, and solid‐state NMR spectroscopy confirmed that a new crystalline form was being produced. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3319–3330, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23200 · 3.01 Impact Factor
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    ABSTRACT: Many boronic acid‐containing molecules are currently under investigation as possible therapeutics. An increase in the knowledge of the physical and chemical properties of these compounds will lead to their improved formulation into usable dosage forms. The current study describes the formation and characterization of a boronic acid anhydride, called a boroxine. The model boronic acid, 4‐methoxybenzeneboronic acid is used. The current study demonstrates the utility of thermal (differential scanning calorimetry and thermogravimetric analysis) and spectral (solid‐state nuclear magnetic resonance and ultraviolet spectroscopy) methods to quantitate and characterize the boronic acid and its boroxine, validated against definitive structures solved by single‐crystal X‐ray diffraction. The present work also demonstrates that the hydrolysis of the boroxine in the presence of water is very rapid in a time scale relative to drug substance manufacture and product formulation. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:3190–3198, 2012
    Journal of Pharmaceutical Sciences 09/2012; 101(9). DOI:10.1002/jps.23207 · 3.01 Impact Factor

Publication Stats

7k Citations
807.38 Total Impact Points

Institutions

  • 2014–2015
    • Janssen Research & Development, LLC
      Raritan, New Jersey, United States
  • 2002–2013
    • Johnson & Johnson
      Нью-Брансуик, New Jersey, United States
  • 2003–2010
    • Janssen Pharmaceutica
      Beersse, Flemish, Belgium
  • 1982–2009
    • University of Florida
      • • College of Pharmacy
      • • Department of Medicinal Chemistry
      Gainesville, FL, United States
  • 2006–2008
    • Association for Molecular Pathology
      베서스다, Maryland, United States
  • 2005
    • California Institute of Technology
      • Division of Chemistry and Chemical Engineering
      Pasadena, CA, United States
  • 1995
    • Albert Einstein College of Medicine
      New York City, New York, United States
  • 1992
    • University of Iceland
      Reikiavik, Capital Region, Iceland