Towards a more desirable dry powder inhaler formulation: large spray-dried mannitol microspheres outperform small microspheres.

Abstract:

PURPOSE:To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. METHODS:Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid-state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance. RESULTS:All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM. CONCLUSION:Particle shape and solid-state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Kaialy W,Hussain T,Alhalaweh A,Nokhodchi A

doi

10.1007/s11095-013-1132-2

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

60-76

issue

1

eissn

0724-8741

issn

1573-904X

journal_volume

31

pub_type

杂志文章
  • The effect of immunosuppression by total-body irradiation on the pharmacodynamics of centrally active drugs in rats.

    abstract::The aim of this investigation was to assess whether immunosuppression induced by total-body irradiation (TBI) affects the pharmacodynamics of centrally acting drugs. Female Sabra rats were exposed to a single dose of gamma irradiation (5.3 Gy). Four days later, when both the cellular and the humoral immune responses w...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1018928329824

    authors: Hoffman A,Alfon J,Habib G,Pinto E,Gorodetsky R

    更新日期:1994-05-01 00:00:00

  • Tissue distribution of indinavir administered as solid lipid nanocapsule formulation in mdr1a (+/+) and mdr1a (-/-) CF-1 mice.

    abstract:PURPOSE:Due to protease inhibitor (PI) efflux transport by P-glycoprotein (P-gp), insufficient PI concentrations result in low ongoing HIV replication in the so-called virus sanctuaries (brain and testes). The aim of the present study was to evaluate indinavir-loaded nanocapsules (Ind-LNC) including Solutol HS15, an ex...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-005-7147-6

    authors: Pereira de Oliveira M,Garcion E,Venisse N,Benoit JP,Couet W,Olivier JC

    更新日期:2005-11-01 00:00:00

  • Influence of crystallizing and non-crystallizing cosolutes on trehalose crystallization during freeze-drying.

    abstract:PURPOSE:To study the influence of crystallizing and non-crystallizing cosolutes on the crystallization behavior of trehalose in frozen solutions and to monitor the phase behavior of trehalose dihydrate and mannitol hemihydrate during drying. METHODS:Trehalose (a lyoprotectant) and mannitol (a bulking agent) are widely...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-010-0221-8

    authors: Sundaramurthi P,Suryanarayanan R

    更新日期:2010-11-01 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

  • Polymer-Based and pH-Sensitive Nanobiosensors for Imaging and Therapy of Acidic Pathological Areas.

    abstract::Nanobiosensors with high sensitivity and specificity have shown great potential in the detection of diseases. The incorporation of therapeutic agents with nanobiosensors allows the simultaneous diagnosis and therapy of diseases. The delivery of nanobiosensors and therapeutic agents using polymers is a common strategy ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-016-1944-y

    authors: Li Y,Yang HY,Lee DS

    更新日期:2016-10-01 00:00:00

  • A Radioimmunoassay Procedure for the Determination of the Antiviral Nucleoside DHPG (9-[(l,3-Dihydroxy-2-propoxy)-methyl]guanine) in Plasma or Serum.

    abstract::A procedure is described that is suitable for the radioimmunoassay (RIA) of 9-[(l,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) in plasma or serum at concentrations as low as 0.7 ng/ml (2.75 × 10(-9) M). Antiserum was prepared by coupling DHPG monohemisuccinate to bovine serum albumin and immunizing rabbits with the re...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/A:1016397520991

    authors: Nerenberg C,McClung S,Martin J,Fass M,La Fargue J,Kushinsky S

    更新日期:1986-04-01 00:00:00

  • Inhibition of P-glycoprotein: rapid assessment of its implication in blood-brain barrier integrity and drug transport to the brain by an in vitro model of the blood-brain barrier.

    abstract:PURPOSE:The objective of this work was to assess, in vitro, the passage of P-glycoprotein dependent drugs across brain capillary endothelial cells, when these drugs are associated with a reversing agent. METHODS:An in vitro model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1011913723928

    authors: Fenart L,Buée-Scherrer V,Descamps L,Duhem C,Poullain MG,Cecchelli R,Dehouck MP

    更新日期:1998-07-01 00:00:00

  • Glycine crystallization during freezing: the effects of salt form, pH, and ionic strength.

    abstract:PURPOSE:The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. METHODS:Crystallization was studied by thermal analysis, microscopy, x-ra...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016223101872

    authors: Akers MJ,Milton N,Byrn SR,Nail SL

    更新日期:1995-10-01 00:00:00

  • Synthetic glycopeptide-based delivery systems for systemic gene targeting to hepatocytes.

    abstract:PURPOSE:To design, synthesize, and test synthetic glycopeptide-based delivery systems for gene targeting to hepatocytes by systemic administration. METHODS:All peptides were synthesized by the solid phase method developed using Fmoc chemistry on a peptide synthesizer. The binding of galactosylated peptides to HepG2 ce...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1007533121682

    authors: Anwer K,Logan M,Tagliaferri F,Wadhwa M,Monera O,Tung CH,Chen W,Leonard P,French M,Proctor B,Wilson E,Singhal A,Rolland A

    更新日期:2000-04-01 00:00:00

  • Cyclodextrin sulfates: characterization as polydisperse and amorphous mixtures.

    abstract::Alpha- and beta-cyclodextrins and their hydroxypropyl derivatives were converted by the reaction with chlorosulfonic acid in pyridine to the corresponding sulfates. Cyclodextrin sulfates were shown by fast-atom bombardment mass spectrometry (negative ion mode, triethanolamine matrix) to be mixtures with nearly symmetr...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015854402122

    authors: Pitha J,Mallis LM,Lamb DJ,Irie T,Uekama K

    更新日期:1991-09-01 00:00:00

  • Establishment and characterization of the transformants stably-expressing MDR1 derived from various animal species in LLC-PK1.

    abstract:PURPOSE:Stable transformants expressing human multidrug resistance 1 (MDR1), monkey MDR1, canine MDR1, rat MDR1a, rat MDR1b, mouse mdr1a, and mouse mdr1b in LLC-PK1 were established to investigate species differences in P-glycoprotein (P-gp, ABCB1) mediated efflux activity. METHODS:The seven cDNAs of MDR1 from five an...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-006-0285-7

    authors: Takeuchi T,Yoshitomi S,Higuchi T,Ikemoto K,Niwa S,Ebihara T,Katoh M,Yokoi T,Asahi S

    更新日期:2006-07-01 00:00:00

  • Pharmaceutical Potential of a Novel Chitosan Derivative Schiff Base with Special Reference to Antibacterial, Anti-Biofilm, Antioxidant, Anti-Inflammatory, Hemocompatibility and Cytotoxic Activities.

    abstract:PURPOSE:Chitosan and its derivatives possess several unique properties relevant in the field of pharmaceutics and medicinal chemistry. This study aimed to evaluate the pharmaceutical performance of an innovative chitosan derivative, methyl acrylate chitosan bearing p-nitrobenzaldehyde (MA*CS*pNBA) Schiff base. METHODS...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2535-x

    authors: Ali SS,Kenawy ER,Sonbol FI,Sun J,Al-Etewy M,Ali A,Huizi L,El-Zawawy NA

    更新日期:2018-11-07 00:00:00

  • In Vivo Stability of Therapeutic Proteins.

    abstract::Significant efforts are made to characterize molecular liabilities and degradation of the drug substance (DS) and drug product (DP) during various product life-cycle stages. The in vivo fate of a therapeutic protein is usually only considered in terms of pharmacokinetics (PKs) and pharmacodynamics (PDs). However, the ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-019-2689-1

    authors: Schuster J,Koulov A,Mahler HC,Detampel P,Huwyler J,Singh S,Mathaes R

    更新日期:2020-01-03 00:00:00

  • A pharmacokinetic model of intravenously administered hyaluronan in sheep.

    abstract::Hyaluronan (HA: hyaluronic acid) is produced in the interstitium and reaches the blood circulation through the lymph. It is rapidly eliminated by means of specific receptors on liver endothelium. The elimination characteristics of intravenously administered HA were studied in 10 conscious sheep at the normal plasma HA...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1015982204926

    authors: Lebel L,Fraser JR,Kimpton WS,Gabrielsson J,Gerdin B,Laurent TC

    更新日期:1989-08-01 00:00:00

  • Evidence for LHRH-receptor expression in human airway epithelial (Calu-3) cells and its role in the transport of an LHRH agonist.

    abstract:PURPOSE:To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist. METHODS:Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LH...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/b:pham.0000029294.70707.74

    authors: Koushik K,Bandi N,Sundaram S,Kompella UB

    更新日期:2004-06-01 00:00:00

  • Inhibition of tumor angiogenesis by tumstatin: insights into signaling mechanisms and implications in cancer regression.

    abstract::Growing tumors develop additional new blood vessels to meet the demand for adequate nutrients and oxygen, a process called angiogenesis. Cancer is a highly complex disease promoted by excess angiogenesis; interfering with this process poses for an attractive approach for controlling tumor growth. This hypothesis led t...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-008-9634-z

    authors: Sudhakar A,Boosani CS

    更新日期:2008-12-01 00:00:00

  • Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration.

    abstract:PURPOSE:Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS:In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tob...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-014-1361-z

    authors: De Cock RF,Allegaert K,Brussee JM,Sherwin CM,Mulla H,de Hoog M,van den Anker JN,Danhof M,Knibbe CA

    更新日期:2014-10-01 00:00:00

  • Pharmacokinetic analysis and antiepileptic activity of tetra-methylcyclopropane analogues of valpromide.

    abstract:PURPOSE:The described structure pharmacokinetic pharmacodynamic relationships (SPPR) study explored the utilization of tetramethylcyclopropane analogues of valpromide (VPD), or tetramethylcyclopropane carboxamide derivatives of valproic acid (VPA) as new antiepileptics. METHODS:The study was carried out by investigati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016055517724

    authors: Bialer M,Hadad S,Kadry B,Abdul-Hai A,Haj-Yehia A,Sterling J,Herzig Y,Yagen B

    更新日期:1996-02-01 00:00:00

  • Investigation into the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate for carrier based dry powder inhaler formulations.

    abstract:PURPOSE:To investigate the influence of primary crystallization conditions on the mechanical properties and secondary processing behaviour of fluticasone propionate (FP) for carrier based dry powder inhaler (DPI) formulations. METHODS:Young's modulus of FP crystals produced using different anti-solvents was determined...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-011-0640-1

    authors: Kubavat HA,Shur J,Ruecroft G,Hipkiss D,Price R

    更新日期:2012-04-01 00:00:00

  • Niclosamide is a Negative Allosteric Modulator of Group I Metabotropic Glutamate Receptors: Implications for Neuropathic Pain.

    abstract:PURPOSE:Novel therapeutics are greatly needed that target specific pathological receptors and pathways involved in Neuropathic Pain (NP). Extending our previous work published in this Journal on Group I metabotropic glutamate receptor (mGluR) modulators, we now investigate the therapeutic potential of niclosamide in mo...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-2027-9

    authors: Ai N,Wood RD,Yang E,Welsh WJ

    更新日期:2016-12-01 00:00:00

  • Use of in vivo animal models to assess pharmacokinetic drug-drug interactions.

    abstract::Animal models are used commonly in various stages of drug discovery and development to aid in the prospective assessment of drug-drug interaction (DDI) potential and the understanding of the underlying mechanism for DDI of a drug candidate. In vivo assessments in an appropriate animal model can be very valuable, when ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审

    doi:10.1007/s11095-010-0157-z

    authors: Tang C,Prueksaritanont T

    更新日期:2010-09-01 00:00:00

  • Population Pharmacokinetic Modelling of Morphine, Gabapentin and their Combination in the Rat.

    abstract:PURPOSE:The combination of morphine and gabapentin seems promising for the treatment of postoperative and neuropathic pain. Despite the well characterised pharmacodynamic interaction, little is known about possible pharmacokinetic interactions. The aim of this study was to evaluate whether co-administration of the two ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-016-1988-z

    authors: Papathanasiou T,Juul RV,Gabel-Jensen C,Kreilgaard M,Lund TM

    更新日期:2016-11-01 00:00:00

  • Measuring The Bipolar Charge Distributions of Fine Particle Aerosol Clouds of Commercial PMDI Suspensions Using a Bipolar Next Generation Impactor (bp-NGI).

    abstract:PURPOSE:To measure the charge to mass (Q/M) ratios of the impactor stage masses (ISM) from commercial Flixotide™ 250 μg Evohaler, containing fluticasone propionate (FP), Serevent™ 25 μg Evohaler, containing salmeterol xinafoate (SX), and a combination Seretide™ 250/25 μg (FP/SX) Evohaler metered dose inhalers (MDIs). M...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-018-2544-9

    authors: Rowland M,Cavecchi A,Thielmann F,Kulon J,Shur J,Price R

    更新日期:2018-11-26 00:00:00

  • Chemical degradation kinetics of recombinant hirudin (HV1) in aqueous solution: effect of pH.

    abstract:PURPOSE:To gain information on the chemical stability pattern and the kinetics of the degradation of recombinant hirudin variant HV1 (rHir), a thrombin-specific inhibitor protein of 65 amino acids, in aqueous solution as a function of pH. METHODS:Stability of rHir was monitored at 50 degrees C in the framework of a cl...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1011918108849

    authors: Gietz U,Alder R,Langguth P,Arvinte T,Merkle HP

    更新日期:1998-09-01 00:00:00

  • Adhesion of powders for inhalation: an evaluation of drug detachment from surfaces following deposition from aerosol streams.

    abstract:PURPOSE:To evaluate micronized powder retention and detachment from inhaler surfaces following reproducible deposition by impaction, coupled with centrifugal particle detachment (CPD). METHODS:Micronized albuterol sulfate (AS) and beclomethasone dipropionate (BDP) were aerosolized as dry powders and deposited by casca...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1014451203619

    authors: Clarke MJ,Peart J,Cagnani S,Byron PR

    更新日期:2002-03-01 00:00:00

  • Differences in the intracellular distribution of acid-sensitive doxorubicin-protein conjugates in comparison to free and liposomal formulated doxorubicin as shown by confocal microscopy.

    abstract:PURPOSE:To investigate differences in the cellular uptake and intracellular distribution of protein-bound doxorubicin in comparison to free doxorubicin and a liposomal formulation (CAELYX) METHODS: LXFL 529 lung carcinoma cells were incubated with an acid-sensitive transferrin and albumin conjugate of doxorubicin, a st...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1011018525121

    authors: Beyer U,Rothern-Rutishauser B,Unger C,Wunderli-Allenspach H,Kratz F

    更新日期:2001-01-01 00:00:00

  • In vitro gastrointestinal lipolysis of four formulations of piroxicam and cinnarizine with the self emulsifying excipients Labrasol and Gelucire 44/14.

    abstract:PURPOSE:Labrasol and Gelucire 44/14 are defined admixtures of acylglycerols and PEG esters which are substrates for digestive lipases. METHODS:We investigated their in vitro gastrointestinal lipolysis to understand which compounds are, after digestion, responsible for keeping poorly water-soluble drugs in solution. Th...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-009-9906-2

    authors: Fernandez S,Chevrier S,Ritter N,Mahler B,Demarne F,Carrière F,Jannin V

    更新日期:2009-08-01 00:00:00

  • Correlation among agonist dose, rate of import, and transcriptional activity of liganded progesterone receptor B isoform in living cells.

    abstract:PURPOSE:To determine the correlation among progesterone dose, rate of import of progesterone-occupied progesterone receptor (PR) complexes into the nucleus of cells, and transcriptional activity of progesterone-PR complexes. METHODS:Live cell imaging and time-lapse microscopy of green fluorescent protein-tagged PR wer...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1026127015761

    authors: Li H,Yan G,Kern SE,Lim CS

    更新日期:2003-10-01 00:00:00

  • Effects of hypothermia on drug absorption.

    abstract::The in situ rat gut technique was used to study the effects of hypothermia on the intestinal absorption of a 1 mg/ml solution of sodium pentobarbital in 0.01 M phosphate buffer (pH 6.0). Male Sprague-Dawley rats weighing between 300 and 370 g were exposed to an atmosphere of helox (helium:oxygen, 80:20) at 0-4 degrees...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1023/a:1016416413780

    authors: Stavchansky S,Tung IL

    更新日期:1987-06-01 00:00:00

  • Computational Fluid Dynamics (CFD) Simulations of Spray Drying: Linking Drying Parameters with Experimental Aerosolization Performance.

    abstract:PURPOSE:The purpose of this study was to develop a new computational fluid dynamics (CFD)-based model of the complex transport and droplet drying kinetics within a laboratory-scale spray dryer, and relate CFD-predicted drying parameters to powder aerosolization metrics from a reference dry powder inhaler (DPI). METHOD...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章

    doi:10.1007/s11095-020-02806-y

    authors: Longest PW,Farkas D,Hassan A,Hindle M

    更新日期:2020-05-21 00:00:00