Formulation and performance of danazol nano-crystalline suspensions and spray dried powders.

Abstract:

PURPOSE:This study focuses on the formulation optimization, in vitro and in vivo performance of differently sized nano-crystalline liquid suspensions and spray-dried powders of a poorly soluble BCS class II compound i.e. Danazol. METHODS:A DoE approach was utilized to optimize stabilizer concentration and formulate danazol (BCS class II) nano-crystalline suspensions and dry powders via wet milling followed by spray drying. Solubility studies were performed to select best stabilizers. Particle size, PXRD, contact angle measurement and in vitro dissolution were utilized in characterization of the liquid and spray-dried powder formulations. RESULTS:The liquid nano-crystalline suspensions followed particle size-dependent dissolution rates i.e. faster dissolution for smaller crystals. The spray-dried nano-crystal powders did not show fast dissolution profiles compared to the liquid nano-crystalline suspension. The poor dissolution of the spray-dried powder correlated to its high LogP value (i.e. LogP 4.53) and poor wetting (or polar surface-area). In vivo bioavailability studies showed superior performance of the liquid nano-crystalline suspensions compared to other milled and un-milled formulations. CONCLUSION:Wet-milling and spray-drying optimization for danazol nano-crystalline suspension was performed. This study indicates that drug candidates with high LogP values and low polar surface area may not be suitable for formulation as dry nano-crystals.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Kumar S,Jog R,Shen J,Zolnik B,Sadrieh N,Burgess DJ

doi

10.1007/s11095-014-1567-0

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

1694-703

issue

5

eissn

0724-8741

issn

1573-904X

journal_volume

32

pub_type

杂志文章
  • Buccal absorption. III. Simultaneous diffusion and metabolism of an aminopeptidase substrate in the hamster cheek pouch.

    abstract::The simultaneous diffusion and metabolism of the D- and L-isomers of the aminopeptidase substrate, leucine-p-nitroanilide (LPNA), were examined in vitro in the hamster cheek pouch. L-LPNA was completely hydrolyzed during diffusion across the cheek pouch, whereas D-LPNA crossed the cheek pouch intact. The metabolic bar...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015949614437

    authors: Garren KW,Topp EM,Repta AJ

    更新日期:1989-11-01 00:00:00

  • Fatty acid-RGD peptide amphiphile micelles as potential paclitaxel delivery carriers to α(v)β₃ integrin overexpressing tumors.

    abstract:PURPOSE:To design and synthesize fatty acid-RGD peptide amphiphiles with ADA linker for their potential delivery of hydrophobic drugs like paclitaxel targeted to α(v)β(3) integrin overexpressing tumors. METHODS:Four amphiphiles - C16 or C18 fatty acid-RGD peptide and ADA linker were designed and synthesized. CMC, size...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0830-5

    authors: Javali NM,Raj A,Saraf P,Li X,Jasti B

    更新日期:2012-12-01 00:00:00

  • Effects of configuration around the chiral carbon atoms on the crystal properties of ephedrinium and pseudoephedrinium salicylates.

    abstract::The physicochemical properties and crystal structures of the crystalline salts formed by the interaction of an achiral anion, salicylate, with homochiral and racemic ephedrinium and pseudoephedrinium cations were determined. The interaction of ephedrinium or pseudoephedrinium with salicylate in aqueous solution yielde...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018945401484

    authors: Duddu SP,Grant DJ

    更新日期:1994-11-01 00:00:00

  • Oxaliplatin degradation in the presence of chloride: identification and cytotoxicity of the monochloro monooxalato complex.

    abstract:PURPOSE:To study the degradation of oxaliplatin in chloride media and evaluate the cytotoxicity of oxaliplatin in normal and chloride-deficient medium. METHODS:The products of the reaction of oxaliplatin with chloride were separated on a Hypercarb S column with a mobile phase containing 40% methanol in 0.05 M ammonia ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/b:pham.0000026444.67883.83

    authors: Jerremalm E,Hedeland M,Wallin I,Bondesson U,Ehrsson H

    更新日期:2004-05-01 00:00:00

  • Jejunal absorption and metabolism of R/S-verapamil in humans.

    abstract:PURPOSE:The purpose of this human intestinal perfusion study was to investigate the transport and metabolism of R/S-verapamil in the human jejunum (in vivo). METHODS:A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut perfusion tube in 12 healthy volunteers. Each perfusion lasted for 200 mi...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1011916329863

    authors: Sandström R,Karlsson A,Knutson L,Lennernäs H

    更新日期:1998-06-01 00:00:00

  • Site- and stereospecific ocular drug delivery by sequential enzymatic bioactivation.

    abstract::Intraocular enzymes convert the ketoxime analogues of some beta-adrenergic blockers via a sequential bioactivation process involving hydrolysis to the corresponding ketones followed by reduction to the aryloxyaminoalcohols, which then exert known and predictable physiological and pharmacological effects only at the si...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015863521513

    authors: Bodor N,Prokai L

    更新日期:1990-07-01 00:00:00

  • Improved intestinal absorption of an enteric-coated sodium ursodeoxycholate formulation.

    abstract::A new enteric-coated formulation of sodium ursodeoxycholate was prepared and administered to man. The barrier film disintegrates and releases the drug only at pH > or = 5.5. The sodium salt of glycoursodeoxycholate was also prepared and encapsulated like ursodeoxycholate. Serum levels of ursodeoxycholate and glycourso...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018907825281

    authors: Roda A,Roda E,Marchi E,Simoni P,Cerrè C,Pistillo A,Polimeni C

    更新日期:1994-05-01 00:00:00

  • Enhanced protein delivery from photopolymerized hydrogels using a pseudospecific metal chelating ligand.

    abstract:PURPOSE:This study was conducted to investigate the cause of incomplete protein release from photopolymerized poly(ethylene glycol) (PEG) hydrogels and verify the protein-protection mechanism provided by iminodiacetic acid (IDA). METHODS:The in vitro release of bovine serum albumin (BSA) from PEG hydrogels prepared un...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-9395-x

    authors: Lin CC,Metters AT

    更新日期:2006-03-01 00:00:00

  • Cancer immunotherapy and nanomedicine.

    abstract::The immune system has the ability to recognize and kill pre-cancer and cancer cells. However, with the immune system's surveillance, the survival tumor cells learn how to escape the immune system after immunoselection. Cancer immunotherapy develops strategies to overcome these problems. Nanomedicine applications in ca...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-010-0258-8

    authors: Sheng WY,Huang L

    更新日期:2011-02-01 00:00:00

  • Dissolving Microneedle Patches for Dermal Vaccination.

    abstract::The dermal route is an attractive route for vaccine delivery due to the easy skin accessibility and a dense network of immune cells in the skin. The development of microneedles is crucial to take advantage of the skin immunization and simultaneously to overcome problems related to vaccination by conventional needles (...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-017-2223-2

    authors: Leone M,Mönkäre J,Bouwstra JA,Kersten G

    更新日期:2017-11-01 00:00:00

  • Early prediction of pharmaceutical oxidation pathways by computational chemistry and forced degradation.

    abstract:PURPOSE:To show, using a model study, how electronic structure theory can be applied in combination with LC/UV/MS/MS for the prediction and identification of oxidative degradants. METHODS:The benzyloxazole 1, was used to represent an active pharmaceutical ingredient for oxidative forced degradation studies. Bond disso...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/b:pham.0000041469.96466.12

    authors: Reid DL,Calvitt CJ,Zell MT,Miller KG,Kingsmill CA

    更新日期:2004-09-01 00:00:00

  • Multi-compartmental nanoparticles-in-emulsion formulation for macrophage-specific anti-inflammatory gene delivery.

    abstract:PURPOSE:To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy. METHODS:Solid nanoparticles-in-emulsion (NiE) multi-compartmental delivery system was designed using plasmid DNA-encapsulated type B gelatin nanoparticles suspended in the...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0677-9

    authors: Attarwala H,Amiji M

    更新日期:2012-06-01 00:00:00

  • Pharmacokinetics of recombinant human interferon-beta ser in healthy volunteers and its effect on serum neopterin.

    abstract::The pharmacokinetics of and biologic response modification by recombinant human interferon-beta ser (rIFN-beta ser) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta ser followed by a single or eight consecutive daily 90 x 10(6) IU subcuta...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018902120023

    authors: Chiang J,Gloff CA,Yoshizawa CN,Williams GJ

    更新日期:1993-04-01 00:00:00

  • Physiologically based pharmacokinetic model for composite nanodevices: effect of charge and size on in vivo disposition.

    abstract:PURPOSE:To characterize temporal exposure and elimination of 5 gold/dendrimer composite nanodevices (CNDs) (5 nm positive, negative, and neutral, 11 nm negative, 22 nm positive) in mice using a physiologically based mathematical model. METHODS:400 ug of CNDs is injected intravenously to mice bearing melanoma cell line...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-012-0784-7

    authors: Mager DE,Mody V,Xu C,Forrest A,Lesniak WG,Nigavekar SS,Kariapper MT,Minc L,Khan MK,Balogh LP

    更新日期:2012-09-01 00:00:00

  • Assay for hydralazine as its stable p-nitrobenzaldehyde hydrazone.

    abstract::A new method of analysis for the antihypertensive drug, hydralazine, is introduced. The assay involves the addition of p-nitrobenzaldehyde to blood samples containing hydralazine, to form a stable Schiff's base, hydralazine p-nitrobenzaldehyde hydrazone. The derivative is extracted from the blood into hexane and the s...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015915812987

    authors: Semple HA,Tam YK,Tin S,Coutts RT

    更新日期:1988-06-01 00:00:00

  • Quantitative assessment of intestinal first-pass metabolism of oral drugs using portal-vein cannulated rats.

    abstract:PURPOSE:To evaluate the impact of intestinal first-pass metabolism (Fg) by cytochrome P4503A (CYP3A) and uridine 5'-diphosphate-glucuronosyltransferases (UGT) on in vivo oral absorption of their substrate drugs. METHODS:CYP3A and UGT substrates were orally administered to portal-vein cannulated (PV) rats to evaluate t...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-014-1489-x

    authors: Matsuda Y,Konno Y,Hashimoto T,Nagai M,Taguchi T,Satsukawa M,Yamashita S

    更新日期:2015-02-01 00:00:00

  • Enhanced bioavailability of cefoxitin using palmitoyl L-carnitine. I. Enhancer activity in different intestinal regions.

    abstract::The conditions under which the absorption enhancer palmitoyl L-carnitine chloride (PCC) improved the bioavailability of the poorly absorbed antibiotic cefoxitin throughout the rat intestine has been studied. Cefoxitin alone was appreciably absorbed only in the duodenum (31% vs less than 7% elsewhere). PCC solutions (3...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018977021183

    authors: Sutton SC,LeCluyse EL,Cammack L,Fix JA

    更新日期:1992-02-01 00:00:00

  • Composite fibrin scaffolds increase mechanical strength and preserve contractility of tissue engineered blood vessels.

    abstract:OBJECTIVES:We recently demonstrated that fibrin-based tissue engineered blood vessels (TEV) exhibited vascular reactivity, matrix remodeling and sufficient strength for implantation into the veins of an ovine animal model, where they remained patent for 15 weeks. Here we present an approach to improve the mechanical pr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-007-9499-6

    authors: Yao L,Liu J,Andreadis ST

    更新日期:2008-05-01 00:00:00

  • Synthesis and Characterization of Nanocomposite Microparticles (nCmP) for the Treatment of Cystic Fibrosis-Related Infections.

    abstract:PURPOSE:Pulmonary antibiotic delivery is recommended as maintenance therapy for cystic fibrosis (CF) patients who experience chronic infections. However, abnormally thick and sticky mucus present in the respiratory tract of CF patients impairs mucus penetration and limits the efficacy of inhaled antibiotics. To overcom...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-1921-5

    authors: Wang Z,Meenach SA

    更新日期:2016-08-01 00:00:00

  • Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy.

    abstract::Over the last few decades, intraperitoneal (IP) local drug delivery, providing high drug concentrations with prolonged retention in the peritoneal cavity, has opened a new horizon for the management of life-threatening peritoneal disorders, such as peritoneal carcinomatosis (PC). However, clinical translation of this ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-020-02818-8

    authors: Alavi S,Haeri A,Mahlooji I,Dadashzadeh S

    更新日期:2020-06-03 00:00:00

  • Novel Approach for the Bioequivalence Assessment of Topical Cream Formulations: Model-Based Analysis of Tape Stripping Data Correctly Concludes BE and BIE.

    abstract:PURPOSE:The purpose of this study was (a) to suggest a novel dermatopharmacokinetic (DPK) approach from which pharmacokinetic parameters relevant to the bioequivalence (BE) assessment of a topical formulation can be deduced while circumventing the need for numerous measurements and assumptions, and (b) to investigate w...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-019-2724-2

    authors: Ozdin D,Kanfer I,Ducharme MP

    更新日期:2020-01-02 00:00:00

  • Biliary excretion of glycyrrhizin in rats: kinetic basis for multiplicity in bile canalicular transport of organic anions.

    abstract:PURPOSE:To examine the presence of multiplicity for the biliary excretion of xenobiotic conjugates, we studied the disposition of glycyrrhizin (GR), which has glucuronide within its molecular structure and has the ability to inhibit the biliary excretion of liquiritigenin (LG) glucuronides. METHODS:GR was administered...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016033124819

    authors: Shimamura H,Suzuki H,Tagaya O,Horie T,Sugiyama Y

    更新日期:1996-12-01 00:00:00

  • Studies on the excretion of diazepam and nordazepam into milk for the prediction of milk-to-plasma drug concentration ratios.

    abstract::The influence of varying protein and fat content in milk of New Zealand White rabbits on the milk-to-plasma drug concentration (M/P) ratio of diazepam was studied. At various time points after littering, a bolus dose (1.5 mg/kg) followed by a 26-hr infusion (1.8 mg/h) of diazepam was administered to freely moving rabb...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015809418284

    authors: Stebler T,Guentert TW

    更新日期:1992-10-01 00:00:00

  • Differential molar heat capacities to test ideal solubility estimations.

    abstract:PURPOSE:Calculation of the ideal solubility of a crystalline solute in a liquid solvent requires knowledge of the difference in the molar heat capacity at constant pressure of the solid and the supercooled liquid forms of the solute, delta Cp. Since this parameter is not usually known, two assumptions have been used to...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1012148910975

    authors: Neau SH,Bhandarkar SV,Hellmuth EW

    更新日期:1997-05-01 00:00:00

  • Synthesis of prostaglandin E(1) phosphate derivatives and their encapsulation in biodegradable nanoparticles.

    abstract:PURPOSE:Prostaglandin E(1) (PGE(1)) is an effective treatment for peripheral vascular diseases. The encapsulation of PGE(1) in nanoparticles for its sustained-release would improve its therapeutic effect and quality of life (QOL) of patients. METHODS:In order to encapsulate PGE(1) in nanoparticles prepared with a poly...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-009-9891-5

    authors: Takeda M,Maeda T,Ishihara T,Sakamoto H,Yuki K,Takasaki N,Nishimura F,Yamashita T,Tanaka K,Takenaga M,Igarashi R,Higaki M,Yamakawa N,Okamoto Y,Ogawa H,Otsuka M,Mizushima Y,Mizushima T

    更新日期:2009-07-01 00:00:00

  • Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.

    abstract:PURPOSES:To evaluate the effects of component contents in different colistin methanesulfonate (CMS) formulas on their clinical pharmacokinetics of the prodrug CMS and the formed colistin. METHODS:Two CMS formulas (CTTQ and Parkedale) were investigated in a single dose, randomized, open-label, crossover study conducted...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-021-02991-4

    authors: Fan YX,Chen YC,Li Y,Yu JC,Bian XC,Li X,Li WZ,Guo BN,Wu HL,Liu XF,Wang Y,Xu XY,Hu JL,Wang JJ,Wu XJ,Cao GY,Wu JF,Xue CJ,Feng J,Zhang YY,Zhang J

    更新日期:2021-01-26 00:00:00

  • Accurate determination of skin flux from flow-through diffusion cell data.

    abstract:PURPOSE:The goal of this investigation was to demonstrate whether the intrinsic flux of a drug diffusing across a membrane mounted in a flow-through diffusion cell may be accurately and easily determined by accounting for the accumulation in the receiver chamber. METHODS:Mathematical modeling, applied to transdermal d...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016216611809

    authors: Harrison DJ,Knutson K

    更新日期:1995-12-01 00:00:00

  • Osmotic-driven release kinetics of bioactive therapeutic proteins from a biodegradable elastomer are linear, constant, similar, and adjustable.

    abstract:PURPOSE:The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial gro...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-006-9750-6

    authors: Gu F,Neufeld R,Amsden B

    更新日期:2006-04-01 00:00:00

  • Predicting skin permeability.

    abstract::Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015810312465

    authors: Potts RO,Guy RH

    更新日期:1992-05-01 00:00:00

  • Noninvasive Imaging of Liposomal Delivery of Superparamagnetic Iron Oxide Nanoparticles to Orthotopic Human Breast Tumor in Mice.

    abstract:PURPOSE:Magnetic resonance imaging (MRI) is widely used for diagnostic imaging in preclinical studies and in clinical settings. Considering the intrinsic low sensitivity and poor specificity of standard MRI contrast agents, the enhanced delivery of MRI tracers into tumors is an important challenge to be addressed. This...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-015-1736-9

    authors: Kato Y,Zhu W,Backer MV,Neoh CC,Hapuarachchige S,Sarkar SK,Backer JM,Artemov D

    更新日期:2015-11-01 00:00:00