Formulation design, challenges, and development considerations for fixed dose combination (FDC) of oral solid dosage forms.

Abstract:

:Fixed dose combination (FDC) products are common in the treatment of hypertension, diabetes, human immunodeficiency virus, and tuberculosis. They make it possible to combine two or more drug molecules with different modes of pharmacological actions in a single dosing unit and optimize the treatment. From a patient perspective, they offer convenience, reduced dosing unit burden, and cost savings. From a clinical perspective, aging population in developed countries will need multiple medications to treat age related diseases and co-morbidities. FDC products simplify dosing regimen and enhance patient compliance. As outlined in the article, the number of FDC products has grown over the years and the trend is likely to continue. This review article gives an overview to pharmaceutical scientists about recent trends in the formulation development of the FDC products and provides decision trees to select most optimum formulation development strategy. While some formulation technologies such as multi-layer tablets, multiparticulate systems, active film coating, and hot-melt granulation are discussed in more detail, a few specialized technologies are also introduced briefly to the readers.

journal_name

Pharm Dev Technol

authors

Desai D,Wang J,Wen H,Li X,Timmins P

doi

10.3109/10837450.2012.660699

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

1265-76

issue

6

eissn

1083-7450

issn

1097-9867

journal_volume

18

pub_type

杂志文章,评审
  • Improvement of the material motion in a rotary processor.

    abstract::The purpose of this paper is to reject or to confirm the hypothesis that the influence of the water addition rate on the size and size distribution of pellets is caused by insufficient spreading of the added water at higher water addition rates. To overcome insufficient spreading of the added water, the agitation in t...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837459609031431

    authors: Vertommen J,Jaucot B,Rombaut P,Kinget R

    更新日期:1996-12-01 00:00:00

  • Effect of degree of methoxylation and particle size on compression properties and compactibility of pectin powders.

    abstract::This study examines the effect of the degree of methoxylation (DM) and particle size on compression properties and compactibility of pectin powders. A powder classification system based on sequential handling of compression parameters was applied. A single size fraction (90-125 μm) of pectin powders with DM values ran...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2010.535831

    authors: Salbu L,Bauer-Brandl A,Alderborn G,Tho I

    更新日期:2012-05-01 00:00:00

  • Physicochemical characterization of native glycyl-l-histidyl-l-lysine tripeptide for wound healing and anti-aging: a preformulation study for dermal delivery.

    abstract::This study investigates the physicochemical properties of glycyl-histidyl-lysine-copper (GHK-Cu) to support the development of a formulation for effective topical delivery. The solubility and distribution coefficients (log D) were investigated using conventional methods and GHK concentrations were quantified with a va...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2014.979944

    authors: Badenhorst T,Svirskis D,Wu Z

    更新日期:2016-03-01 00:00:00

  • Synthesis, characterization, and kinetic release study of methotrexate loaded mPEG-PCL polymersomes for inhibition of MCF-7 breast cancer cell line.

    abstract::In this study, we designed a polymersome system for the controlled release of methotrexate (MTX) as an anticancer drug with the objective of improving the loading efficiency of the drug in polymersomes as well as achievement of an efficient control on the release rate of drug from nanocarriers. We synthesized mono met...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2018.1425433

    authors: Nosrati H,Adinehvand R,Manjili HK,Rostamizadeh K,Danafar H

    更新日期:2019-01-01 00:00:00

  • The impact of crystallinity on Brequinar sodium hygroscopicity.

    abstract::The hygroscopicity of Brequinar sodium, an organ transplant immunosuppressant, at 75% relative humidity highly depends on the crystal form or crystallinity of the drug substance. Hygroscopicity and ease of water uptake of three lots of Brequinar sodium were investigated. Those lots contained different impurities at le...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837459609031417

    authors: Wu LS,Pang J,Hussain MA

    更新日期:1996-04-01 00:00:00

  • Correlation between the viscoelastic properties of the gel layer of swollen HPMC matrix tablets and their in vitro drug release.

    abstract::Drug release from hydroxypropyl methylcellulose (HPMC) hydrophilic matrix tablets is controlled by drug diffusion through the gel layer of the matrix-forming polymer upon hydration, matrix erosion or combination of diffusion and erosion mechanisms. In this study, the relationship between viscoelastic properties of the...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2016.1257022

    authors: Hamed R,Al Baraghthi T,Sunoqrot S

    更新日期:2018-11-01 00:00:00

  • Novel potential drug against T. cruzi and its interaction with surfactant micelles.

    abstract::The interaction of 5-nitro-2-furfurilylidene benzhydrazide (5NFB), potential anti-trypanosomal compound, with micellar solutions was studied. The results indicated that 50 mug of 5NFB completely kills 20 million T. cruzi epimastigote cells within 3 days, whereas the same amount of benznidazole kills 30% of the cells a...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450701212727

    authors: Rangel-Yagui CO,Hsu HW,Barbosa LR,Caetano W,Pessoa A Jr,Tavares LC,Itri R

    更新日期:2007-01-01 00:00:00

  • Amorphization of itraconazole by inorganic pharmaceutical excipients: comparison of excipients and processing methods.

    abstract::The aim of this study was to investigate the effects of solid carriers and processing routes on the properties of amorphous solid dispersions of itraconazole. Three solid carriers with a range of surface properties were studied, (1) a mesoporous silicate, magnesium aluminum silicate (Neusilin US2), (2) a nonporous sil...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2014.959181

    authors: Grobelny P,Kazakevich I,Zhang D,Bogner R

    更新日期:2015-01-01 00:00:00

  • Comments on prediction of the aqueous solubility using the general solubility equation (GSE) versus a genetic algorithm and a support vector machine model.

    abstract::The general solubility equation (GSE) is the state-of-the-art method for estimating the aqueous solubilities of organic compounds. It is an extremely simple equation that expresses aqueous solubility as a function of only two inputs: the octanol-water partition coefficient calculated by readily available softwares lik...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2017.1321663

    authors: Alantary D,Yalkowsky S

    更新日期:2018-09-01 00:00:00

  • Effect of sample preparation method on quantification of polymorphs using PXRD.

    abstract::The purpose of this study was to improve the sensitivity and accuracy of quantitative analysis of polymorphic mixtures. Various techniques such as hand grinding and mixing (in mortar and pestle), air jet milling and ball milling for micronization of particle and mixing were used to prepare binary mixtures. Using these...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450903286511

    authors: Alam S,Patel S,Bansal AK

    更新日期:2010-09-01 00:00:00

  • Solid-state characterization and dissolution properties of Fluvastatin sodium salt hydrates.

    abstract::The present study reports the solid-state properties of Fluvastatin sodium salt crystallized from different solvents for comparison with crystalline forms of the commercially available raw material and United States Pharmacopeia (USP) reference standard. Fluvastatin (FLV) samples were characterized by several techniqu...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2012.727000

    authors: Borgmann SH,Bernardi LS,Rauber GS,Oliveira PR,Campos CE,Monti G,Cuffini SL,Cardoso SG

    更新日期:2013-03-01 00:00:00

  • Decreasing acute toxicity and suppressing colorectal carcinoma using Sorafenib-loaded nanoparticles.

    abstract::Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug.Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were e...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2020.1718704

    authors: Li N,Chen Y,Sun H,Huang T,Chen T,Jiang Y,Yang Q,Yan X,Wu M

    更新日期:2020-06-01 00:00:00

  • Evaluation of co-processed excipients used for direct compression of orally disintegrating tablets (ODT) using novel disintegration apparatus.

    abstract::The compendial method of evaluation of orodispersible tablets (ODT) is the same disintegration test as for conventional tablets. Since it does not reflect the disintegration process in the oral cavity, alternative methods are proposed that are more related to in vivo conditions, e.g. modified dissolution paddle appara...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2012.710238

    authors: Brniak W,Jachowicz R,Krupa A,Skorka T,Niwinski K

    更新日期:2013-03-01 00:00:00

  • Drug-polymer mixed coating: a new approach for controlling drug release rates in pellets.

    abstract::A new approach to developing a drug-polymer mixed coat for highly water-soluble diltiazem pellets was investigated at different coating levels. Drug layering and the coating procedures were performed using a bottom spray fluidized bed coater. Drug pellets were coated with Eudragit NE40 (NE40) alone and in combination ...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450500464008

    authors: Nisar ur Rahman,Yuen KH,Khan NA,Wong JW

    更新日期:2006-02-01 00:00:00

  • Rapid formulation screening with a Multipart Microscale Fluid bed Powder processor.

    abstract::The aim of this study was to investigate early formulation screening in small scale with a miniaturized fluid bed device. Altogether eight different batches were granulated in a Multipart Microscale Fluid bed Powder processor (MMFP) with constant process conditions using electrostatic atomization. Atomization voltage ...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837451003739271

    authors: Kivikero N,Murtomaa M,Antikainen O,Hatara J,Juppo AM,Sandler N

    更新日期:2011-08-01 00:00:00

  • Preparation and characterization of nimesulide containing nanocrystal formulations.

    abstract::The aim of this study was to develop and characterize nanocrystal formulation containing nimesulide. Physical mixture of drug and excipient (nimesulide:pluronic F127, 1:0.5) was also prepared to compare the efficiency of formulations. The physicochemical characteristics of the formulations were determined by means of ...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2012.663390

    authors: Gülsün T,Budak C,Vural I,Sahin S,Öner L

    更新日期:2013-05-01 00:00:00

  • Preparation of celecoxib tablet by hot melt extrusion technology and application of process analysis technology to discriminate solubilization effect.

    abstract::The aim of this study was to prepare various types of solid dispersions (SDs) by the hot-melt extrusion technique. Next, process analytical technology (PAT) such as Fourier transform-infrared (FT-IR) and Raman and near infrared (NIR) spectroscopy were applied to determine the solubilization effect. The SDs and its tab...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2020.1723023

    authors: Hwang I,Renuka V,Lee JH,Weon KY,Kang CY,Lee BJ,Park JB

    更新日期:2020-06-01 00:00:00

  • Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid.

    abstract::The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheo...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1081/pdt-120018490

    authors: Rossi S,Sandri G,Ferrari F,Bonferoni MC,Caramella C

    更新日期:2003-01-01 00:00:00

  • Tablets prepared by single-step granulation/tabletting: interparticulate binding mechanism and stability.

    abstract::The binding mechanism of tablets prepared by single-step granulation/tabletting (SSGT), a novel technique for the production of tablets, was evaluated. SSGT yielded hard tablets having a short disintegration time due to their porous, spongelike internal structure. Calculation of the interaction factor and electrical c...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1081/pdt-65690

    authors: Vermeire A,Keleb EI,Kiekens F,Van Driessche I,Hoste S,Remon JP,Vervaet C

    更新日期:2005-01-01 00:00:00

  • Prediction of tablet hardness and porosity using near-infrared diffuse reflectance spectroscopy as a nondestructive method.

    abstract::The main objective of this research is to use the near-infrared diffuse reflectance method to evaluate and quantify the effects of hardness and porosity on the near-infrared spectras of tablets. To develop a model equation, validate the model and test the model predictive ability. Seven theophylline tablet formulation...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1081/pdt-120024689

    authors: Donoso M,Kildsig DO,Ghaly ES

    更新日期:2003-01-01 00:00:00

  • Robustness testing in pharmaceutical freeze-drying: inter-relation of process conditions and product quality attributes studied for a vaccine formulation.

    abstract:CONTEXT:The recent US Food and Drug Administration (FDA) legislation has introduced the evaluation of the Design Space of critical process parameters in manufacturing processes. In freeze-drying, a "formulation" is expected to be robust when minor deviations of the product temperature do not negatively affect the final...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2011.581287

    authors: Schneid SC,Stärtzel PM,Lettner P,Gieseler H

    更新日期:2011-11-01 00:00:00

  • Novel platens to measure the hardness of a pentagonal shaped tablet.

    abstract::Tablet hardness, a measure of the breaking force of a tablet, is based on numerous factors. These include the shape of the tablet and the mode of the application of force. For instance, when a pentagonal-shaped tablet was tested with a traditional hardness tester with flat platens, there was a large variation in hardn...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2016.1219370

    authors: Malladi J,Sidik K,Wu S,McCann R,Dougherty J,Parab P,Carragher T

    更新日期:2017-03-01 00:00:00

  • Novel organogels for topical delivery of naproxen: design, physicochemical characteristics and in vitro drug permeation.

    abstract::Taking into account possible irritation of the skin upon contact with naproxen (NPX) crystals and lower bioavailability after administration of the suspended or ionized drug, the aim of the work was to design and characterize novel and easy-to-formulate gels with the entirely dissolved drug in the acidic form. The for...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2015.1135342

    authors: Osmałek T,Milanowski B,Froelich A,Górska S,Białas W,Szybowicz M,Kapela M

    更新日期:2017-06-01 00:00:00

  • A new method for evaluating the dissolution of orodispersible films.

    abstract::The aim of this research was to develop and assess a new dissolution apparatus for orodispersible films (ODFs). The new apparatus was based on a flow-through cell design which requires only a limited amount of dissolution medium and can automatically collect samples in short-time intervals. Compared with the dissoluti...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2014.882936

    authors: Xia Y,Chen F,Zhang H,Luo C

    更新日期:2015-05-01 00:00:00

  • Taste masking of naproxen sodium granules by fluid-bed coating.

    abstract::The taste of oral dosage forms is an important argument regarding patient's compliance and acceptability. For this reason, it is often necessary to mask an undesirable and unpleasant taste of an active pharmaceutical ingredient. The purpose of this study was to mask the taste of naproxen sodium by a new fluid-bed coat...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837450.2012.757784

    authors: Stange U,Führling C,Gieseler H

    更新日期:2014-03-01 00:00:00

  • Percolation theory and the role of maize starch as a disintegrant for a low water-soluble drug.

    abstract::The objective of the present work is to investigate the presence or absence of a critical concentration of maize starch according to the percolation theory for a truly ternary system with respect to a minimum disintegration time. The results of this study show that the application of percolation theory is not limited ...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450601166494

    authors: Kimura G,Puchkov M,Betz G,Leuenberger H

    更新日期:2007-01-01 00:00:00

  • Application of a quality-by-design approach for utilizing sodium stearyl fumarate as a taste-masking agent in dextromethorphan hydrobromide orally disintegrating tablets.

    abstract::Orally dissolving tablets (ODTs) represent one of the recent advances in drug delivery. The foremost objective of this study was to optimize the utilization of lubricant sodium stearyl fumarate in the preparation of dextromethorphan hydrobromide ODTs with enhanced taste-masking properties. The simple blending of sodiu...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2019.1579228

    authors: Mahrous GM,Ibrahim MA,Mostafa HF,Elzayat EM

    更新日期:2019-07-01 00:00:00

  • Influence of loading volume of mefenamic acid on granules and tablet characteristics using a compaction simulator.

    abstract::Mefenamic acid (MA), a poorly water-soluble drug, was used as a model substance to investigate granules and tablet characteristics to be optimized for the loading volume of MA (0-74.1% v/v) in the formulation including lactose monohydrate/maize starch (7/3) as excipients. The compactibility of granules increased with ...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450701702941

    authors: Kimura G,Betz G,Leuenberger H

    更新日期:2008-01-01 00:00:00

  • In vitro permeation study of a mucoadhesive drug delivery system for controlled delivery of nonoxynol-9.

    abstract::A carbopol 934P-based drug delivery system (AmDDS) was developed to achieve the dual-controlled delivery of Nonoxynol-9 (N-9), a spermicidal agent, and EDTA, a potentiator of spermicidal activity. This gel-type system made intimate contact with vaginal mucosa and maintained an effective drug concentration within the v...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.3109/10837459609029888

    authors: Lee CH,Chien YW

    更新日期:1996-07-01 00:00:00

  • Dual drug nanocrystals loaded microparticles for fixed dose combination of simvastatin and ezetimibe.

    abstract::Dual drug nanocrystals loaded nano embedded microparticles (DNEMs) were prepared for fixed dose combination of simvastatin (SIM) and ezetimibe (EZE) using NanoCrySP technology. The purpose was to generate nanonized SIM and EZE dispersed in matrix of single crystallization inducing excipient and investigate their in vi...

    journal_title:Pharmaceutical development and technology

    pub_type: 杂志文章

    doi:10.1080/10837450.2019.1669181

    authors: Nandi S,Kaur A,Bansal AK

    更新日期:2020-01-01 00:00:00