Isothermal Crystallization Monitoring and Time-Temperature-Transformation of Amorphous GDC-0276: Differential Scanning Calorimetric and Rheological Measurements.

Abstract:

:Cold crystallization of amorphous pharmaceuticals is an important aspect in the search to stabilize amorphous or glassy compounds used as amorphous pharmaceutical ingredients (APIs). In the present work, we report results for the isothermal crystallization of the compound GDC-0276 based on differential scanning calorimetric and rheometric measurements. The kinetics of isothermal crystallization from the induction time to the completion of crystallization can be described by the classic Johnson-Mehl-Avrami (JMA) equation. The time-temperature-transformation (TTT) diagrams were constructed for two time points-that of induction and that of completion of crystallization. The results show that the rheological measurement for GDC-0276 has a better overall sensitivity in detection of the early stage nucleation and, consequently, detects the onset of crystallization sooner than does the differential scanning calorimetry. Rheological measurements were also used to obtain the temperature dependence of the viscosity of GDC-0276 and the relevant parameters were used in a modified form of the JMA model to describe the temperature dependence of the crystal induction and completion times, that is, the TTT diagram for the material. In the modification, we assumed that the kinetics followed the viscosity to the 0.75 power as suggested by the recent work of Huang et al. (Huang, C., et al., J. Chem. Phys.2018,149, 054503). The relationship and the possible impact on crystallization kinetics of the break-down of the Stokes-Einstein relation in glass-forming liquids are discussed. From the crystallization kinetics modeling, the solid-liquid interfacial surface tension σSL was obtained for GDC-0276 and was compared with that obtained from the melting point depression measurements of the material confined in nanoporous glasses. The differences between the values from the two methods are discussed.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Cheng S,Chakravarty P,Nagapudi K,McKenna GB

doi

10.1021/acs.molpharmaceut.0c00776

subject

Has Abstract

pub_date

2021-01-04 00:00:00

pages

158-173

issue

1

eissn

1543-8384

issn

1543-8392

journal_volume

18

pub_type

杂志文章
  • Pharmacokinetic-Pharmacodynamic Correlation and Brain Penetration of sec-Butylpropylacetamide, a New CNS Drug Possessing Unique Activity against Status Epilepticus.

    abstract::sec-Butylpropylacetamide (SPD) is the amide derivative of valproic acid (VPA). SPD possess a wide-spectrum anticonvulsant profile better than that of VPA and blocks status epilepticus (SE) induced by pilocarpine and organophosphates. The activity of SPD on SE is better than that of benzodiazepines (BZDs) in terms of t...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b00221

    authors: Mawasi H,Bibi D,Shekh-Ahmad T,Shaul C,Blotnik S,Bialer M

    更新日期:2016-07-05 00:00:00

  • Pycup--a bifunctional, cage-like ligand for (64)Cu radiolabeling.

    abstract::In developing targeted probes for positron emission tomography (PET) based on (64)Cu, stable complexation of the radiometal is key, and a flexible handle for bioconjugation is highly advantageous. Here, we present the synthesis and characterization of the chelator pycup and four derivatives. Pycup is a cross-bridged c...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400686z

    authors: Boros E,Rybak-Akimova E,Holland JP,Rietz T,Rotile N,Blasi F,Day H,Latifi R,Caravan P

    更新日期:2014-02-03 00:00:00

  • Hydrophobically modified dendrons: developing structure-activity relationships for DNA binding and gene transfection.

    abstract::This paper develops a structure-activity relationship understanding of the way in which surfactant-like dendrons with hydrophilic spermine surface groups and a variety of lipophilic units at their focal points can self-assemble and subsequently bind to DNA with high affinity. The choice of functional group at the foca...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp100260c

    authors: Jones SP,Gabrielson NP,Wong CH,Chow HF,Pack DW,Posocco P,Fermeglia M,Pricl S,Smith DK

    更新日期:2011-04-04 00:00:00

  • Acceleration of Crystal Growth of Amorphous Griseofulvin by Low-Concentration Poly(ethylene oxide): Aspects of Crystallization Kinetics and Molecular Mobility.

    abstract::This study aims to investigate the crystallization behavior and molecular dynamics of amorphous griseofulvin (GSF) in the presence of low-concentration poly(ethylene oxide) (PEO). We observe that the addition of 3% w/w PEO remarkably increases the crystal growth rate of GSF by two orders of magnitude in both the super...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00097

    authors: Shi Q,Zhang C,Su Y,Zhang J,Zhou D,Cai T

    更新日期:2017-07-03 00:00:00

  • Conjugates of superoxide dismutase 1 with amphiphilic poly(2-oxazoline) block copolymers for enhanced brain delivery: synthesis, characterization and evaluation in vitro and in vivo.

    abstract::Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the e...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300496x

    authors: Tong J,Yi X,Luxenhofer R,Banks WA,Jordan R,Zimmerman MC,Kabanov AV

    更新日期:2013-01-07 00:00:00

  • Oral delivery of doxorubicin using novel polyelectrolyte-stabilized liposomes (layersomes).

    abstract::The present study explores the potential of polyelectrolyte-coated liposomes for improving the oral deliverability of doxorubicin (Dox). As a part of formulation strategy, stearyl amine was selected as a formulation component to provide positive charge to liposomes, which were subsequently coated with anionic poly(acr...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300202c

    authors: Jain S,Patil SR,Swarnakar NK,Agrawal AK

    更新日期:2012-09-04 00:00:00

  • Comparison of reversible and nonreversible aqueous-soluble lipidized conjugates of salmon calcitonin.

    abstract::Reversible aqueous lipidization (REAL) at the interdisulfide bond has been shown to improve the deliverability of some peptide drugs. Recently, we developed a nonreversible aqueous lipidization method targeted at the interdisulfide bond of salmon calcitonin (sCT). The resultant derivative had comparable hypocalcemic a...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp8000167

    authors: Cheng W,Lim LY

    更新日期:2008-07-01 00:00:00

  • PEG-PE micelles loaded with paclitaxel and surface-modified by a PBR-ligand: synergistic anticancer effect.

    abstract::Selective ligands to the peripheral benzodiazepine receptor (PBR) may induce apoptosis and cell cycle arrest. An overexpression of PBR in certain cancers allowed us to consider the use of highly selective ligands to PBR for receptor-mediated drug targeting to tumors. With this in mind, we prepared PBR-targeted nanopar...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp800158c

    authors: Musacchio T,Laquintana V,Latrofa A,Trapani G,Torchilin VP

    更新日期:2009-03-01 00:00:00

  • Adjuvant Activity of Poly-ε-caprolactone/Chitosan Nanoparticles Characterized by Mast Cell Activation and IFN-γ and IL-17 Production.

    abstract::Polymeric nanoparticles (NPs) are extremely attractive vaccine adjuvants, able to promote antigen delivery and in some instances, exert intrinsic immunostimulatory properties that enhance antigen specific humoral and cellular immune responses. The poly-ε-caprolactone (PCL)/chitosan NPs were designed with the aim of be...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00730

    authors: Jesus S,Soares E,Borchard G,Borges O

    更新日期:2018-01-02 00:00:00

  • Mapping site-specific changes that affect stability of the N-terminal domain of calmodulin.

    abstract::Biophysical tools have been invaluable in formulating therapeutic proteins. These tools characterize protein stability rapidly in a variety of solution conditions, but in general, the techniques lack the ability to discern site-specific information to probe how solution environment acts to stabilize or destabilize the...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp2004109

    authors: Krause ME,Martin TT,Laurence JS

    更新日期:2012-04-02 00:00:00

  • Enhancing Oral Bioavailability of Cyclic RGD Hexa-peptides by the Lipophilic Prodrug Charge Masking Approach: Redirection of Peptide Intestinal Permeability from a Paracellular to Transcellular Pathway.

    abstract::Hydrophilic peptides constitute most of the active peptides. They mostly permeate via tight junctions (paracellular pathway) in the intestine. This permeability mechanism restricts the magnitude of their oral absorption and bioavailability. We hypothesized that concealing the hydrophilic residues of the peptide using ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00466

    authors: Schumacher-Klinger A,Fanous J,Merzbach S,Weinmüller M,Reichart F,Räder AFB,Gitlin-Domagalska A,Gilon C,Kessler H,Hoffman A

    更新日期:2018-08-06 00:00:00

  • Co-administration of dual-targeting nanoparticles with penetration enhancement peptide for antiglioblastoma therapy.

    abstract::Chemotherapy is an indispensable auxiliary treatment for glioma but highly limited by the existence of both blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). The dysfunctional brain tumor blood vessels and high interstitial pressure in glioma also greatly hindered the accumulation and deep penetration of...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400189j

    authors: Miao D,Jiang M,Liu Z,Gu G,Hu Q,Kang T,Song Q,Yao L,Li W,Gao X,Sun M,Chen J

    更新日期:2014-01-06 00:00:00

  • Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer.

    abstract::Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers of tumors. The aim of the present study was to investigate the effect of oral antifibrotic agent (telmisartan) on tumor uptake and anticancer efficacy of EphA2 receptor targeted liposom...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b00187

    authors: Patel K,Doddapaneni R,Sekar V,Chowdhury N,Singh M

    更新日期:2016-06-06 00:00:00

  • The effect of multiple N-methylation on intestinal permeability of cyclic hexapeptides.

    abstract::Recent progress in peptide synthesis simplified the synthesis of multiple N-methylation of peptides. To evaluate how multiple N-methylation affects the bioavailability of peptides, a poly alanine cyclic hexapeptide library (n = 54), varying in the number of N-methyl (N-Me) groups (1-5 groups) and their position, was s...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp1003306

    authors: Ovadia O,Greenberg S,Chatterjee J,Laufer B,Opperer F,Kessler H,Gilon C,Hoffman A

    更新日期:2011-04-04 00:00:00

  • Highly supersaturated solutions from dissolution of amorphous itraconazole microparticles at pH 6.8.

    abstract::Dry powders from aqueous dispersions, formed by antisolvent precipitation, dissolved to form solutions with supersaturation values up to 12 in 10 min at pH 6.8 with sodium dodecyl sulfate micelles. Itraconazole/hydroxypropylmethylcellulose (HPMC) aqueous particle dispersions were salt flocculated and filtered to produ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp800106a

    authors: Matteucci ME,Paguio JC,Miller MA,Williams RO 3rd,Johnston KP

    更新日期:2009-03-01 00:00:00

  • (64)Cu- and (68)Ga-Based PET Imaging of Folate Receptor-Positive Tumors: Development and Evaluation of an Albumin-Binding NODAGA-Folate.

    abstract::A number of folate-based radioconjugates have been synthesized and evaluated for nuclear imaging purposes of folate receptor (FR)-positive tumors and potential therapeutic application. A common shortcoming of radiofolates is, however, a significant accumulation of radioactivity in the kidneys. This situation has been ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b00143

    authors: Farkas R,Siwowska K,Ametamey SM,Schibli R,van der Meulen NP,Müller C

    更新日期:2016-06-06 00:00:00

  • The contribution of atom accessibility to site of metabolism models for cytochromes P450.

    abstract::Three different types of atom accessibility descriptors are investigated in relation to site of metabolism predictions. To enable the integration of local accessibility we have constructed 2DSASA, a method for the calculation of the atomic solvent accessible surface area that is independent of 3D coordinates. The meth...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3005116

    authors: Rydberg P,Rostkowski M,Gloriam DE,Olsen L

    更新日期:2013-04-01 00:00:00

  • Reduced skin photosensitivity with meta-tetra(hydroxyphenyl)chlorin-loaded micelles based on a poly(2-ethyl-2-oxazoline)-b-poly(d,l-lactide) diblock copolymer in vivo.

    abstract::Photodynamic therapy (PDT) is a light-induced chemical reaction that produces localized tissue damage for the treatment of cancers and other nonmalignant conditions. The activation of photosensitizers in a target tissue is accomplished with a specific light source in the presence of molecular oxygen. In the clinic, pa...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp100060v

    authors: Shieh MJ,Peng CL,Chiang WL,Wang CH,Hsu CY,Wang SJ,Lai PS

    更新日期:2010-08-02 00:00:00

  • Biocompatibility and efficacy of oligomaltose-grafted poly(ethylene imine)s (OM-PEIs) for in vivo gene delivery.

    abstract::Polycationic polymers like poly(ethylene imine)s (PEIs) are extensively explored for the nonviral transfer of DNA or small RNAs (siRNAs). To enhance biocompatibility and alter pharmacokinetic properties, hyperbranched PEI was recently grafted with the nonligand oligosaccharides maltose or maltotriose at various degree...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400479g

    authors: Gutsch D,Appelhans D,Höbel S,Voit B,Aigner A

    更新日期:2013-12-02 00:00:00

  • Delivery of polysaccharides using polymer particles: implications on size-dependent immunogenicity, opsonophagocytosis, and protective immunity.

    abstract::Bacterial capsular polysaccharides are components of many modern vaccines, but they are weakly immunogenic. Herein, we describe the delivery of pneumococcal capsular polysaccharide serotype-1 (PCP-1) in polylactide polymeric particles to enhance its immunogenicity. Immunization with PCP-1-entrapped particles elicited ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400589q

    authors: Anish C,Khan N,Upadhyay AK,Sehgal D,Panda AK

    更新日期:2014-03-03 00:00:00

  • Solubility Challenges in High Concentration Monoclonal Antibody Formulations: Relationship with Amino Acid Sequence and Intermolecular Interactions.

    abstract::The purpose of this work was to elucidate the molecular interactions leading to monoclonal antibody self-association and precipitation and utilize biophysical measurements to predict solubility behavior at high protein concentration. Two monoclonal antibodies (mAb-G and mAb-R) binding to overlapping epitopes were inve...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00336

    authors: Pindrus M,Shire SJ,Kelley RF,Demeule B,Wong R,Xu Y,Yadav S

    更新日期:2015-11-02 00:00:00

  • Disposition of nanoparticles and an associated lipophilic permeant following topical application to the skin.

    abstract::The objective was to determine the disposition of polymer nanoparticles and an associated, lipophilic, model "active" component on and within the skin following topical application. Polystyrene and poly(methyl methacrylate) nanoparticles containing covalently bound fluorescein methacrylate and dispersed Nile Red were ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp9001188

    authors: Wu X,Price GJ,Guy RH

    更新日期:2009-09-01 00:00:00

  • Pyropheophorbide A and c(RGDyK) comodified chitosan-wrapped upconversion nanoparticle for targeted near-infrared photodynamic therapy.

    abstract::Near-infrared (NIR)-to-visible upconversion nanoparticle (UCNP) has shown promising prospects in photodynamic therapy (PDT) as a drug carrier or energy donor. In this work, a photosensitizer pyropheophorbide a (Ppa) and RGD peptide c(RGDyK) comodified chitosan-wrapped NaYF(4):Yb/Er upconversion nanoparticle UCNP-Ppa-R...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp200590y

    authors: Zhou A,Wei Y,Wu B,Chen Q,Xing D

    更新日期:2012-06-04 00:00:00

  • In Vitro Characterization of the Biomimetic Properties of Poly(dimethylsiloxane) To Simulate Oral Drug Absorption.

    abstract::The potential use of poly(dimethylsiloxane) (PDMS) as an in vitro biomimetic analogue of the passive drug absorption process in the human gastrointestinal tract (GI) is assessed. PDMS is biomimetic because of similarities in small molecule transport, such as mechanism, ionization selectivity, lipophilicity. Nine molec...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00798

    authors: Sinko PD,Gidley D,Vallery R,Lamoureux A,Amidon GL,Amidon GE

    更新日期:2017-12-04 00:00:00

  • Differential cytosolic delivery and presentation of antigen by listeriolysin O-liposomes to macrophages and dendritic cells.

    abstract::Delivery of antigenic protein to the cytosol of antigen-presenting cells (APCs), such as macrophages (MPhi) and dendritic cells (DCs), is required for an efficient CD8 T-cell-mediated immune response. We have previously shown that co-encapsulation of antigenic protein inside pH-sensitive liposomes with listeriolysin O...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp049896v

    authors: Stier EM,Mandal M,Lee KD

    更新日期:2005-01-01 00:00:00

  • Inhibition of hepatitis C virus by the cyanobacterial protein Microcystis viridis lectin: mechanistic differences between the high-mannose specific lectins MVL, CV-N, and GNA.

    abstract::Plant or microbial lectins are known to exhibit potent antiviral activities against viruses with glycosylated surface proteins, yet the mechanism(s) by which these carbohydrate-binding proteins exert their antiviral activities is not fully understood. Hepatitis C virus (HCV) is known to possess glycosylated envelope p...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400399b

    authors: Kachko A,Loesgen S,Shahzad-Ul-Hussan S,Tan W,Zubkova I,Takeda K,Wells F,Rubin S,Bewley CA,Major ME

    更新日期:2013-12-02 00:00:00

  • Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles.

    abstract::Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00904

    authors: Aldawsari HM,Dhaliwal HK,Aljaeid BM,Alhakamy NA,Banjar ZM,Amiji MM

    更新日期:2019-01-07 00:00:00

  • Increasing cancer-specific gene expression by targeting overexpressed α5β1 integrin and upregulated transcriptional activity of NF-κB.

    abstract::We developed a modular multifunctional nonviral gene delivery system by targeting the overexpressed cancer surface receptor α5β1 integrin and the upregulated transcriptional activity of the cancer resistance mediating transcription factor NF-κB, thereby introducing a new form of transcriptional targeting. NF-κB regula...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400535v

    authors: Adil MM,Levine RM,Kokkoli E

    更新日期:2014-03-03 00:00:00

  • Prediction of Response to Therapy for Autoimmune/Inflammatory Diseases Using an Activated Macrophage-Targeted Radioimaging Agent.

    abstract::The ability to select patients who will respond to therapy is especially acute for autoimmune/inflammatory diseases, where the costs of therapies can be high and the progressive damage associated with ineffective treatments can be irreversible. In this article we describe a clinical test that will rapidly predict the ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00134

    authors: Kelderhouse LE,Robins MT,Rosenbalm KE,Hoylman EK,Mahalingam S,Low PS

    更新日期:2015-10-05 00:00:00

  • Systemic delivery of stable siRNA-encapsulating lipid vesicles: optimization, biodistribution, and tumor suppression.

    abstract::Lipid-based nanoparticles are considered as promising candidates for delivering siRNA into the cytoplasm of targeted cells. However, in vivo efficiency of these nanoparticles is critically dependent on formulation strategies of lipid-siRNA complexes. Adsorption of serum proteins to lipid-siRNA complexes and its charge...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp500677x

    authors: Dar GH,Gopal V,Rao NM

    更新日期:2015-02-02 00:00:00