Impact of product design parameters on in vitro release from intrauterine systems.


:Polydimethylsiloxane (PDMS)-based levonorgestrel intrauterine systems (LNG-IUSs) contain a large amount of potent LNG, and therefore it is important to understand the impact of product design parameters on the in vitro and in vivo performance to ensure safety and efficacy, as well as to avoid serious side effects resulting from dose dumping. LNG-IUS is a complex drug-device combination product, and its formulation design, requires consideration of additional factors such as device configuration and dimensions, in addition to formulation and processing parameters. In this study, ten qualitatively (Q1) and quantitatively (Q2) equivalent LNG-IUSs were manufactured with differences in source (supplier) and dimensions (i.e., thickness) of the outer membrane, drug particle size, dimensions of the drug reservoir (i.e., inner diameter), as well as configuration of the entire IUS. A real-time in vitro release testing method was developed for the LNG-IUSs. In addition, an accelerated release testing method was developed using hydro-alcoholic media in order to reduce the time associated with formulation design. Source variations and thickness of their outer membranes had a great impact on the in vitro drug release from the LNG-IUSs. It was demonstrated that the thicker the outer membrane, the slower the drug release rate. The physicochemical properties of the outer membranes obtained from different sources were characterized to understand their impact on the in vitro drug release of the LNG-IUSs. The composition and mechanical strength may play a role in differences in drug release. The LNG-IUS formulation prepared with the larger drug particle size showed a slightly slower daily release rate. The drug release rates from the compositionally equivalent LNG-IUSs linearly correlated to the surface area of the corresponding drug reservoirs. Another factor that affected the drug release rate was the configuration of the entire IUS. It was shown that the placement of the outer membrane was significant, i.e. whether the ends of the drug reservoir were covered or not. It is important to note that real-time release showed zero-order release kinetics over the test period of approximately 900 days. The current study provides a comprehensive understanding of the impact of product design parameters on the in vitro drug release of LNG-IUSs. In addition, the developed real-time and accelerated release testing methods showed good discriminatory ability for compositionally equivalent LNG-IUSs prepared using different product design parameters.


Int J Pharm


Bao Q,Zou Y,Wang Y,Choi S,Burgess DJ




Has Abstract


2020-03-30 00:00:00












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    abstract::Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel met...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章,随机对照试验


    authors: Mohammed D,Crowther JM,Matts PJ,Hadgraft J,Lane ME

    更新日期:2013-01-30 00:00:00

  • Therapeutic efficacy of sustained drug release from chitosan gel on local inflammation.

    abstract::The model anti-inflammatory drug prednisolone (PS) was retained in chitosan (CS) gel beads, which were prepared in a 10% aqueous amino acid solution (pH 9.0). Sustained release of PS from the CS gel beads was observed. Carrageenan solution was injected into air pouches (AP), which were prepared subcutaneously on the d...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Kofuji K,Akamine H,Qian CJ,Watanabe K,Togan Y,Nishimura M,Sugiyama I,Murata Y,Kawashima S

    更新日期:2004-03-19 00:00:00

  • Novel drug delivery strategies for improving econazole antifungal action.

    abstract::Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on th...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章,评审


    authors: Firooz A,Nafisi S,Maibach HI

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  • Properties of solid dispersions of piroxicam in polyvinylpyrrolidone.

    abstract::Solid dispersions of piroxicam were prepared with polyvinylpyrrolidone (PVP) K-17 PF and PVP K-90 by solvent method. The physical state and drug:PVP interaction of solid dispersions and physical mixtures were characterized by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and differential scanning c...

    journal_title:International journal of pharmaceutics

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    authors: Tantishaiyakul V,Kaewnopparat N,Ingkatawornwong S

    更新日期:1999-04-30 00:00:00

  • Influence of acylation on the adsorption of GLP-2 to hydrophobic surfaces.

    abstract::Acylation of proteins with a fatty acid chain has proven useful for prolonging the plasma half-lives of proteins. In formulation of acylated protein drugs, knowledge about the effect of acylation with fatty acids on the adsorption behaviour of proteins at interfaces will be valuable. The aim of this work was to study ...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Pinholt C,Kapp SJ,Bukrinsky JT,Hostrup S,Frokjaer S,Norde W,Jorgensen L

    更新日期:2013-01-02 00:00:00

  • Nanoparticles based on natural, engineered or synthetic proteins and polypeptides for drug delivery applications.

    abstract::Medicine formulations at the nanoscale, referred to as nanomedicines, have managed to overcome key challenges encountered during the development of new medical treatments and entered clinical practice, but considerable improvement in terms of local efficacy and reduced toxicity still need to be achieved. Currently, th...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Georgilis E,Abdelghani M,Pille J,Aydinlioglu E,van Hest JCM,Lecommandoux S,Garanger E

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  • Production of salbutamol sulfate for inhalation by high-gravity controlled antisolvent precipitation.

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Chiou H,Li L,Hu T,Chan HK,Chen JF,Yun J

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  • Micro and nano polycaprolactone particles preparation by pulsed back-and-forward cross-flow batch membrane emulsification for parenteral administration.

    abstract::In the pharmaceutical field, manufacturing processes which are able to make products with tailored size at suitable shear stress conditions and high productivity are important requirements for their industrial application. Cross-flow and premix membrane emulsification are the membrane-based processes generally used fo...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Imbrogno A,Piacentini E,Drioli E,Giorno L

    更新日期:2014-12-30 00:00:00

  • Characterization and compaction behaviour of nimesulide crystal forms.

    abstract::Nimesulide is a typical nonsteroidal anti-inflammatory drug (NSAID), widely used in solid oral formulations. By crystallizing nimesulide from an ethanol solution a crystalline form was obtained, different from the reference sample, as confirmed by X-ray powder diffraction (XRPD), Differential Scanning Calorimetry (DSC...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Di Martino P,Censi R,Barthélémy C,Gobetto R,Joiris E,Masic A,Odou P,Martelli S

    更新日期:2007-09-05 00:00:00

  • Diclofenac-β-cyclodextrin for colonic drug targeting: In vivo performance in rats.

    abstract::The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a susp...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Vieira AC,Serra AC,Veiga FJ,Gonsalves AM,Basit AW,Murdan S

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  • In vitro experiment optimization for measuring tetrahydrocannabinol skin permeation.

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Challapalli PV,Stinchcomb AL

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    authors: Rubinstein I,Onyüksel H

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  • Solid lipid nanoparticles (SLN) of Efavirenz as lymph targeting drug delivery system: Elucidation of mechanism of uptake using chylomicron flow blocking approach.

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    journal_title:International journal of pharmaceutics

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    authors: Makwana V,Jain R,Patel K,Nivsarkar M,Joshi A

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    journal_title:International journal of pharmaceutics

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    authors: Cui Y,Chiang PC,Choo EF,Boggs J,Rudolph J,Grina J,Wenglowsky S,Ran Y

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    journal_title:International journal of pharmaceutics

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    authors: Liu W,Hu M,Liu W,Xue C,Xu H,Yang X

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  • Evaluation of air-interfaced Calu-3 cell layers for investigation of inhaled drug interactions with organic cation transporters in vitro.

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    journal_title:International journal of pharmaceutics

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    authors: Mukherjee M,Pritchard DI,Bosquillon C

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    abstract::In this work, an amphiphilic polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan (PTA-g-CMCS) was designed and synthesized. In aqueous solution, this grafted polymer can self-assemble into spherical micelles with a size ranging from 104 to 285 nm and zeta potential ranging from -12.3 ...

    journal_title:International journal of pharmaceutics

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    authors: Gong XY,Yin YH,Huang ZJ,Lu B,Xu PH,Zheng H,Xiong FL,Xu HX,Xiong X,Gu XB

    更新日期:2012-10-15 00:00:00

  • Preparation and characterisation of hexamidine salts.

    abstract::Hexamidine diisethionate (HEX D) has been used in the personal care industry and in a number of over-the-counter (OTC) drug products as an antimicrobial agent since the 1950's. Recently, the compound has also been investigated for its beneficial effects on skin health. Surprisingly, there is only limited information d...

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    authors: Parisi N,Matts PJ,Lever R,Hadgraft J,Lane ME

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    abstract::The purpose of the present study was to investigate the effect of secondary structure of three model polypeptides on their apparent permeability (P(app)) across a synthetic, microporous membrane. Poly-L-lysine (PL), poly-L-glutamate (PGlu), and poly-L-lysine-L-phenylalanine (1:1) (PLP) were selected because a solution...

    journal_title:International journal of pharmaceutics

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    authors: Salamat-Miller N,Chittchang M,Mitra AK,Johnston TP

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  • Short-duration ocular iontophoresis of ionizable aciclovir prodrugs: A new approach to treat herpes simplex infections in the anterior and posterior segments of the eye.

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  • Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles.

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    authors: Hu Y,Li M,Zhang M,Jin Y

    更新日期:2018-11-15 00:00:00

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    journal_title:International journal of pharmaceutics

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    authors: Pisal DS,Yellepeddi VK,Kumar A,Kaushik RS,Hildreth MB,Guan X,Palakurthi S

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Reginald-Opara JN,Svirskis D,O'Carroll SJ,Sreebhavan S,Dean JM,Wu Z

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Roberts M,Cespi M,Ford JL,Dyas AM,Downing J,Martini LG,Crowley PJ

    更新日期:2007-03-06 00:00:00

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Zhang H,Lou S,Williams GR,Branford-White C,Nie H,Quan J,Zhu LM

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Yang M,Wang P,Huang CY,Ku MS,Liu H,Gogos C

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Engelmann FM,Rocha SV,Toma HE,Araki K,Baptista MS

    更新日期:2007-02-01 00:00:00

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    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Wang YJ,Assaad E,Ispas-Szabo P,Mateescu MA,Zhu XX

    更新日期:2011-10-31 00:00:00

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    abstract::The short half-life and bitter taste of carbinoxamine maleate2 (CAM) lead to poor compliance by pediatric patients who are being treated for allergic rhinitis. To address these issues, carbinoxamine-resin complexes3 (CRCs) were prepared by ion exchange and then coated with Kollicoat SR 30D. The resultant microencapsul...

    journal_title:International journal of pharmaceutics

    pub_type: 杂志文章


    authors: Deng Y,Wang T,Li J,Sun W,He H,Gou J,Wang Y,Yin T,Zhang Y,Tang X

    更新日期:2020-10-15 00:00:00