A study of amorphous molecular dispersions of indomethacin and its sodium salt

Tong, Ping; Zografi, George

doi:10.1002/jps.1150

Cited by 62 publications

(35 citation statements)

References 25 publications

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“…8). Zografi et al, reported an absence of the peak in the 1710 cm j1 region for the sodium salt of indomethacin (33,34). A similar absence of the peak in the 1710 cm j1 region for indomethacin co-ground with Neusilin US2 might suggest the possibility of salt formation.…”

Section: Interaction Of Indomethacin With Neusilin Us2mentioning

confidence: 84%

Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism

2006

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Section: Interaction Of Indomethacin With Neusilin Us2mentioning

confidence: 84%

Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism

2006

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“…Solidification of the melt has been accomplished using different techniques such as rapid quenching over liquid nitrogen (8,9), slow cooling at room temperature (10) or cooling the melt at −5°C/min (11). Other methods to produce amorphous solids include solvent deposition (12), solvent evaporation (9,13), spray drying (14)(15)(16), freeze drying (9,13), and spray-freeze drying (17). Another method that has been successfully used to produce amorphous solids is co-grinding crystalline materials with excipients.…”

Section: Introductionmentioning

confidence: 99%

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Bahl

Bogner

2008

AAPS PharmSciTech

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Abstract. The solubility advantage of indomethacin amorphized by co-grinding with Neusilin US2 in various media was investigated. Physical mixtures of γ-indomethacin and Neusilin US2 (in the ratios 1:1, 1:4 and 1:5) were amorphized at room temperature employing 75% RH in a porcelain jar mill using zirconia balls. The crystallinity of the samples was determined using ATR-FTIR and PXRD. The solubility and dissolution profiles of co-ground powders and crystalline counterparts were evaluated in 0.1 N HCl, water and phosphate buffer (pH 6.8) in a USP type II dissolution apparatus at 250 rpm and 37°C. Very high concentrations of dissolved indomethacin as compared to the solubility of γ-indomethacin (~500 times in water and~3.7 times in phosphate buffer) were attained. However, the presence of other polymorphs detected by PXRD and a change in the pH of the medium made interpretation of the results difficult. In 0.1 N HCl the solubility (i.e., the peak in a concentration versus time plot) of the amorphized drug in a 1:5 ratio with Neusilin increased to 109 times the solubility of crystalline γ-indomethacin alone. An increase in amount of drug and Neusilin in the same ratio added to the dissolution medium also increased peak and plateau dissolution concentrations. The presence of silicic acid and ions (Mg 2+ and Al 3+ ) in the dissolution media were found to cause the increase in the plateau concentration of indomethacin. Amorphization alone does not account for all of the dissolution enhancement; acidity, ions, and silicic acid are major contributors to dissolution enhancement.

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“…Amorphous solids lack the three dimensional long range molecular order characteristics of crystal but may exhibit short range order [26,68,69]. Amorphous materials are further from equilibrium than crystalline materials, are higher energy states and as expected have faster dissolution rates and kinetics or metastable solubilities relative to corresponding crystals [67].…”

Section: Single Component Systemmentioning

confidence: 99%

Drug polymorphism: a review

Saifee¹,

Inamda²,

Dhamecha³

et al. 2010

Int J Health Res

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an online international journal allowing free unlimited access to abstract and full-text of published articles. The journal is devoted to the promotion of health sciences and related disciplines (including medicine, pharmacy, nursing, biotechnology, cell and molecular biology, and related engineering fields). It seeks particularly (but not exclusively) to encourage multidisciplinary research and collaboration among scientists, the industry and the healthcare professionals. It will also provide an international forum for the communication and evaluation of data, methods and findings in health sciences and related disciplines. The journal welcomes original research papers, reviews and case reports on current topics of special interest and relevance. All manuscripts will be subject to rapid peer review. Those of high quality (not previously published and not under consideration for publication) will be published without delay. The maximum length of manuscripts should normally be 10,000 words (20 single-spaced typewritten pages) for review, 6,000 words for research articles, 3,000 for technical notes, case reports, commentaries and short communications. Submission of Manuscript:The International Journal of Health Research uses a journal management software to allow authors track the changes to their submission. All manuscripts must be in MS Word and in English and should be submitted online at http://www.ijhr.org. Authors who do not want to submit online or cannot submit online should send their manuscript by e-mail attachment (in single file) to the editorial office below. Submission of a manuscript is an indication that the content has not been published or under consideration for publication elsewhere. Authors may submit the names of expert reviewers or those they do not want to review their papers. Enquiries AbstractFormulators are charged with the responsibility of formulating a product which is physically and chemically stable, and bioavailable. Solid-state properties including polymorphism, solvate and salt formation can have a profound impact on important properties (solubility & stability) that are essential for successful development of drug candidates. Crystallization of pharmaceutically active ingredients, particularly those that possess multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. Most drugs exhibits structural polymorphism and it is desirable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf-life under a variety of real world storage conditions. There are occasional situations in which development of a meta-stable crystalline or amorphous form is justified to achieve the desired medical benefit. Such situation includes those in which faster dissolution rates or higher concentrations are desired in order to achieve rapid absorption an...

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A study of amorphous molecular dispersions of indomethacin and its sodium salt

Cited by 62 publications

References 25 publications

Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism

Amorphization of Indomethacin by Co-Grinding with Neusilin US2: Amorphization Kinetics, Physical Stability and Mechanism

Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin

Drug polymorphism: a review

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