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Formulation Development (formulation + development)
Selected AbstractsCurrent status of amorphous formulation and other special dosage forms as formulations for early clinical phasesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2009Kohsaku Kawakami Abstract Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2875,2885, 2009 [source] Behaviour of polysorbate 20 during dialysis, concentration and filtration using membrane separation techniquesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2008Hanns-Christian Mahler Abstract During formulation development of a therapeutic protein, combinations of buffers, pH and excipients need to be tested. As the protein bulk solution used for formulation development usually contains a buffer component at a defined pH and potentially one or more excipients already, this bulk requires to be processed. In case low concentrations of non-ionic surfactants, for example polysorbate 20, are already present in the bulk, the surfactant needs to be removed in lab-scale for further development use. The scope of the work was to study the behaviour of low concentrations of polysorbate 20 during membrane separation processes. The first part focuses on evaluating the behaviour of polysorbate 20 during a dialysis process, whereas the second part analyses concentration changes of polysorbate during a membrane concentration process using a stirred cell. The third part analyses potential membrane absorption of polysorbate at sterilizing-grade filters. In conclusion, it was found that polysorbate could not be significantly reduced during a dialysis process and accumulated during a membrane concentration process in unreproducable manner. During sterile filtration, no significant influence on the concentration of polysorbate was measurable. In any case, it is recommendable to quantify the concentration of polysorbate during critical membrane process steps in pharmaceutical industry. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:764,774, 2008 [source] Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer techniqueJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2008Dionysios Douroumis Abstract An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:919,930, 2008 [source] Antibody structure, instability, and formulationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2007Wei Wang Abstract The number of therapeutic monoclonal antibody in development has increased tremendously over the last several years and this trend continues. At present there are more than 23 approved antibodies on the US market and an estimated 200 or more are in development. Although antibodies share certain structural similarities, development of commercially viable antibody pharmaceuticals has not been straightforward because of their unique and somewhat unpredictable solution behavior. This article reviews the structure and function of antibodies and the mechanisms of physical and chemical instabilities. Various aspects of formulation development have been examined to identify the critical attributes for the stabilization of antibodies. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1,26, 2007 [source] Anthrax vaccine powder formulations for nasal mucosal deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Ge Jiang Abstract Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6,8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7,8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:80,96, 2006 [source] Applications of mass spectrometry for the structural characterization of recombinant protein pharmaceuticalsMASS SPECTROMETRY REVIEWS, Issue 3 2007Catherine A. Srebalus Barnes Abstract Therapeutic proteins produced using recombinant DNA technologies are generally complex, heterogeneous, and subject to a variety of enzymatic or chemical modifications during expression, purification, and long-term storage. The use of mass spectrometry (MS) for the evaluation of recombinant protein sequence and structure provides detailed information regarding amino acid modifications and sequence alterations that have the potential to affect the safety and activity of therapeutic protein products. General MS approaches for the characterization of recombinant therapeutic protein products will be reviewed with particular attention given to the standard MS tools available in most biotechnology laboratories. A number of recent examples will be used to illustrate the utility of MS strategies for evaluation of recombinant protein heterogeneity resulting from post-translational modifications (PTMs), sequence variations generated from proteolysis or transcriptional/translational errors, and degradation products which are formed during processing or final product storage. Specific attention will be given to the MS characterization of monoclonal antibodies as a model system for large, glycosylated, recombinant proteins. Detailed examples highlighting the use of MS for the analysis of monoclonal antibody glycosylation, deamidation, and disulfide mapping will be used to illustrate the application of these techniques to a wide variety of heterogeneous therapeutic protein products. The potential use of MS to support the selection of cell line/clone selection and formulation development for therapeutic antibody products will also be discussed. © 2007 Wiley Periodicals, Inc., Mass Spec Rev [source] A simple and rapid method to assess lycopene in multiple layers of skin samplesBIOMEDICAL CHROMATOGRAPHY, Issue 2 2010Luciana B. Lopes Abstract Topical application of lycopene is a convenient way to restore antioxidants depleted from the skin by UV radiation and achieve protection against premature aging and cancer. In this study, a simple, rapid and reproducible method to quantify lycopene in different skin layers was developed, validated and employed to assess this compound after skin penetration studies. Lycopene was extracted from the stratum corneum (SC) and viable epidermis and dermis (ED) by vortex homogenization and bath sonication in a mixture of acetonitrile and methanol (52:48, v/v). Lycopene was assayed by HPLC using a C18 column, and acetonitrile:methanol (52:48, v/v) as mobile phase. The quantification limit of lycopene in samples of SC and ED was 35,ng/mL and the assay was linear from 35 to 2000,ng/mL. Within-day and between-days assays coefficients of variation and relative errors (indicative of precision and accuracy) were less than 15% (or 20% for the limit of quantification). Lycopene recovery from SC and ED was dependent on the spiked concentration: for 50,ng/mL, recoveries were 88.3 and 90.5%; for 100,1000,ng/mL, recoveries were 68.6,74.9%. This method has a potential application for lycopene quantification during formulation development and evaluation in the dermatological field. Copyright © 2009 John Wiley & Sons, Ltd. [source] Second international conference on accelerating biopharmaceutical developmentBIOTECHNOLOGY PROGRESS, Issue 4 2009Coronado, March The Second International Conference on Accelerating Biopharmaceutical Development was held in Coronado, California. The meeting was organized by the Society for Biological Engineering (SBE) and the American Institute of Chemical Engineers (AIChE); SBE is a technological community of the AIChE. Bob Adamson (Wyeth) and Chuck Goochee (Centocor) were co-chairs of the event, which had the theme "Delivering cost-effective, robust processes and methods quickly and efficiently." The first day focused on emerging disruptive technologies and cutting-edge analytical techniques. Day two featured presentations on accelerated cell culture process development, critical quality attributes, specifications and comparability, and high throughput protein formulation development. The final day was dedicated to discussion of technology options and new analysis methods provided by emerging disruptive technologies; functional interaction, integration and synergy in platform development; and rapid and economic purification process development. © This meeting report was written for and published by Landes Bioscience in the journal, mAbs. Reichert JM, Jacob N, Amanullah A. Second International Conference on Accelerating Biopharmaceutical Development: March 9,12, 2009, Coronado, CA USA. mAbs 2009 1(3); http://www. landesbioscience.com/journals/mabs/article/8491 Biotechnol. Prog., 2009 [source] | ||||||||||