Comparison of the mechanical properties of the crystalline and amorphous forms of a drug substance

Hancock, Bruno C.; Carlson, Glenn T.; Ladipo, Dauda D; Langdon, Beth A.; Mullarney, Matthew P.

doi:10.1016/s0378-5173(02)00133-3

Cited by 99 publications

(45 citation statements)

References 14 publications

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“…The bulk drugs should have high brittleness properties and low ductility and elasticity properties [50] to enable efficient size reduction through attrition milling. This deliver option applies to a broad range of drug molecules, with melting points generally 100-350°C and Log P values of 0-5.…”

Section: Formulation and Delivery Aspectsmentioning

confidence: 99%

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

2017

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Abstract. This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

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Section: Formulation and Delivery Aspectsmentioning

confidence: 99%

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

2017

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“…41,42 Amorphous dispersion of daidzein in nanoparticles might be another reason for better absorption. 43,44 Apart from these reasons, more importantly, daidzein complexes may play an important role in absorption. Some studies have demonstrated that phospholipid-drug complexes and cyclodextrin-drug complexes could increase oral bioavailability by improving the liposolubility and solubility of drugs.…”

Section: Dovepressmentioning

confidence: 99%

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability

Ma¹,

Zhao²,

Li³

et al. 2012

IJN

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Abstract:The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, −32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, −18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57-and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties.

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“…A simple general rule, although semi empirical proposed can be used to predict the effect of crystal packing of polymorphs on their compressibility and bonding strength [114][115]. The more stable polymorphs due to its higher packing density, is expected to form stronger interparticle bonds but is harder to deform [104,113,114].…”

Section: Mechanical Properties Of Polymorphs and Amorphous Drug Formsmentioning

confidence: 99%

“…The lack of information on mechanical properties of amorphous drugs may be due to the physical and chemical instability of these forms. One report comparing the mechanical properties of crystalline and amorphous forms of model drug has been published [115].…”

Section: Mechanical Properties Of Polymorphs and Amorphous Drug Formsmentioning

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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Comparison of the mechanical properties of the crystalline and amorphous forms of a drug substance

Cited by 99 publications

References 14 publications

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability

Drug polymorphism: a review

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