The Experts below are selected from a list of 3843 Experts worldwide ranked by ideXlab platform
Paul B Myrdal - One of the best experts on this subject based on the ideXlab platform.
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Preformulation and evaluation of tofacitinib as a therapeutic treatment for asthma
Aaps Pharmscitech, 2019Co-Authors: Usir S Younis, Ernest Vallorz, Kenneth J Addison, Julie G Ledford, Paul B MyrdalAbstract:: Preformulation studies on tofacitinib citrate, a small molecule JAK3 specific inhibitor, have not been previously reported in literature. We therefore conducted several Preformulation studies on tofacitinib citrate, and its free base, to better understand factors that affect its solubility, stability, and solid-state characteristics. Further, the results of the Preformulation studies helped facilitate the development of a nebulized formulation of tofacitinib citrate for inhalational delivery to house dust mite allergen-challenged, BALB/c mice as a potential treatment for eosinophilic asthma. The Preformulation results indicated tofacitinib having a basic pKa of 5.2, with its stability dependent on pH, ionic strength, and temperature. Degradation of tofacitinib follows apparent first-order kinetics. In order to maximize stability of the drug, ionic strength and temperature should be minimized, with an optimal range pH between 2.0 and 5.0. Additionally, our findings demonstrate that tofacitinib citrate can successfully be nebulized at a suitable droplet size for inhalation (1.2 ± 0.2 μm MMAD) through a nose-only chamber. Animals dosed with tofacitinib citrate demonstrated marked reductions in BAL eosinophils and total protein concentrations following HDM challenge. These data suggest that tofacitinib citrate represents the potential to be an effective therapy for eosinophilic asthma.
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Preformulation studies on piperlongumine
PLOS ONE, 2016Co-Authors: Alhassan Aodah, Aaron Pavlik, Kelly L Karlage, Paul B MyrdalAbstract:Piperlongumine is a natural alkaloid extracted from piper plants which has been used traditionally for the treatment of certain diseases. This compound shows interesting in vitro pharmacological activity such as selective anticancer activity and higher cytotoxicity than methotrexate, cyclophosphamide and adriamycin on breast, colon, and osteosarcoma cancers, respectively. However, the physicochemical properties for this compound have not been well characterized. In this research, Preformulation studies for piperlongumine have been performed to determine factors which influence solubility and stability which, in turn, can be used to assist future formulation development. The solubility of piperlongumine in water was found to be approximately 26 μg/ml. Using 10% polysorbate 80 as a surfactant resulted in a 27 fold increase in solubility. Cosolvents and cyclodextrins afforded concentrations of 1 mg/ml and higher. The pH degradation rate profile for piperlongumine at various temperatures shows significant instability of the drug at pH values ≥ 7 and 3, and maximum stability around pH 4. It was estimated that it would take approximately 17 weeks for piperlongumine to degrade by 10% at 25°C, pH 4. Additionally, piperlongumine showed marked photo-degradation upon exposure to an ultraviolet light source, especially in aqueous media.
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Preformulation studies on imexon
Drug Development and Industrial Pharmacy, 2006Co-Authors: P J Kuehl, William L Hoye, Paul B MyrdalAbstract:AbstractImexon is an aziridine containing iminopyrrolidone that, through aziridine ring opening, is able to induce oxidative stress resulting in apoptosis. The main objective of this research was to conduct extensive Preformulation studies on Imexon in order to understand the factors that affect its stability. The results obtained indicate that the stability of Imexon is dependant on pH, ionic strength, temperature, buffer species, and initial concentration. Degradation of Imexon follows apparent first-order degradation kinetics with the primary degradation product resulting from opening of the aziridine ring. In order to maximize stability, ionic strength, temperature, and initial concentration should be minimized, with an optimal range pH between 7.2 and 9.0. Experimentation with other aqueous solutions indicates that Imexon has increased stability in D5W as opposed to normal saline, while it undergoes rapid degradation in 6% H2O2. Imexon is not ionizable between pH 5.0 to 8.5 and has an aqueous solubil...
Ram A Vishwakarma - One of the best experts on this subject based on the ideXlab platform.
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impact of Preformulation on drug development
Expert Opinion on Drug Delivery, 2013Co-Authors: Sonali S Bharate, Ram A VishwakarmaAbstract:Introduction: Preformulation assists scientists in screening lead candidates based on their physicochemical and biopharmaceutical properties. This data is useful for selection of new chemical entities (NCEs) for preclinical efficacy/toxicity studies which is a major section under investigational new drug application. A strong collaboration between discovery and formulation group is essential for selecting right NCEs in order to reduce attrition rate in the late stage development. Areas covered: This article describes the significance of Preformulation research in drug discovery and development. Various crucial Preformulation parameters with case studies have been discussed. Expert opinion: Physicochemical and biopharmaceutical characterization of NCEs is a decisive parameter during product development. Early prediction of these properties helps in selecting suitable physical form (salt, polymorph, etc.) of the candidate. Based on pharmacokinetic and efficacy/toxicity studies, suitable formulation for Phas...
Sonali S Bharate - One of the best experts on this subject based on the ideXlab platform.
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impact of Preformulation on drug development
Expert Opinion on Drug Delivery, 2013Co-Authors: Sonali S Bharate, Ram A VishwakarmaAbstract:Introduction: Preformulation assists scientists in screening lead candidates based on their physicochemical and biopharmaceutical properties. This data is useful for selection of new chemical entities (NCEs) for preclinical efficacy/toxicity studies which is a major section under investigational new drug application. A strong collaboration between discovery and formulation group is essential for selecting right NCEs in order to reduce attrition rate in the late stage development. Areas covered: This article describes the significance of Preformulation research in drug discovery and development. Various crucial Preformulation parameters with case studies have been discussed. Expert opinion: Physicochemical and biopharmaceutical characterization of NCEs is a decisive parameter during product development. Early prediction of these properties helps in selecting suitable physical form (salt, polymorph, etc.) of the candidate. Based on pharmacokinetic and efficacy/toxicity studies, suitable formulation for Phas...
Gerhard Winter - One of the best experts on this subject based on the ideXlab platform.
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thermo optical protein characterization for straightforward Preformulation development
Journal of Pharmaceutical Sciences, 2017Co-Authors: Randy Wanner, Dennis Breitsprecher, Stefan Duhr, Philipp Baaske, Gerhard WinterAbstract:Abstract The determination of protein unfolding and aggregation characteristics during Preformulation is of major significance for the development of biopharmaceuticals. The aim of this study was to investigate the feasibility of a new immobilization- and label-free thermo-optical approach as an orthogonal method for material and time-saving early formulation and drugability screenings. In the experimental setup used, changes in the intrinsic tryptophan fluorescence of the protein were measured during IR laser–induced heating of the samples. This temperature increase leads to characteristic fluorescence changes over time, which can be attributed to separable effects of protein unfolding, aggregation, and precipitation, depending on the stability of the respective formulation. The obtained signals were compared with data from forced degradation and thermal stability measurements and correlated well both with the aggregation propensity and with the reversibility of unfolding in different formulations. These results, gathered with only 4-μL sample volume and 150 s measurement time per formulation, demonstrate potential for general applicability in rapid candidate and formulation selections.
Katharina M Picker-freyer - One of the best experts on this subject based on the ideXlab platform.
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Book review
European Journal of Pharmaceutics and Biopharmaceutics, 2008Co-Authors: Katharina M Picker-freyerAbstract:The book ''Preformulation in Solid Dosage Form Development " edited by Moji Christianah Adeyeye and Harry G. Brittain is a prac-tical handbook, a development course, and a systematical evalua-tion of all aspects of Preformulation at the same time. Especially Brittain gives practical easy accessible examples which the reader can transfer to his own problems. Often questions which occur to the pharmaceutical scientist in Preformulation are asked and thus urge the reader to transfer the presented data to his own problems. The book is clearly structured and is basically organized due to the four stages of Preformulation which follow up each other in a typical Preformulation development. After the introduction the parts ''Preliminary Preformulation " , ''Profiling the drug sub-stance " , ''Development of the ideal formulation " , and ''Beyond Preformulation " systematically approach the different stages of Preformulation. The introduction covers all topics to be considered before pre-formulation and emphasizes the need to think before experiment-ing in order to avoid errors and to save valuable time and money. This fact is also absolutely necessary in early Preformulation and moreover it is advised to use available methods of prediction be-fore performing unnecessary experiments. The proposition of intelligent Preformulation determines the second part ''Preliminary Preformulation " covering molecular physical properties, analytical data analysis, crystallographic char-acteristics, and salt selection and terminates in the use of artificial neural networks (ANN) for intelligent Preformulation design. Questions as 'Which crystal forms are possible?' or 'Which salt is the best?' are essential in early Preformulation and thus determine the development course. The third part deals with the topics related to the drug sub-stance and highlights that a detailed knowledge of the drug sub-stance is essential and determines further Preformulation. Thus the API has to be known and particle morphology has not to be ne-glected and to be analyzed with appropriate methods. Especially the chapter ''Preparation and identification of polymorphs and solvatomorphs " is extremely useful and presents a great many examples described in the literature. In the following chapter problems associated with X-ray diffraction, methods how to work with mixtures and practical suggestions are combined. It presents an overview on the use of X-ray diffraction methods for solid phar-maceutical materials. A description of spectroscopic, thermal, calo-rimetric and solubility methods completes the overview on essential techniques in Preformulation. Besides the advantages and disadvantages of the presented methods advices are given which techniques are used and shall be applied in Preformulation. Recent advances in the determination of glass transition tempera-ture, the application of coupled methods, and the performance of stability measurements are presented accompanied by a great many of useful examples. Finally the development of an ideal formulation is described. After a short introduction highlighting the essential facts what to consider before stating practical studies, drug-excipient interac-tions during solid dosage form development and the methodology or their evaluation are presented. Positive and negative interac-tions are covered accompanied by an up-to-date literature review of a great part of the current advances in Preformulation. The ba-sics of statistics useful for evaluation are given. This fourth part concludes with a comprehensive chapter on general factors to con-sider for dissolution testing, on the importance of batch to batch variation, on biovaiwers, on practical hints for dissolution testing, and on regulatory aspects. The book concludes with the fifth very concentrated part on Preformulation reports and essential regulatory aspects in prefor-mulation. Practical advices how to report as desired by the FDA using Quality by Design (QbA) and applying Process Analytical Technology (PAT) are presented and the importance of the drugs physicochemical properties for regulatory issues is highlighted. As stated in the introduction remarks, the book serves the industry scientists by having the regulatory authorities in mind, however it is also of interest for new and advanced researchers in the field. Overall this newly launched book on Preformulation is as valuable handbook for industrial scientists as well as for all other researchers in the field. For advanced readers the broad cov-erage of literature examples is of special interest.
