An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen

Vergote, Geert; Vervaet, Chris; Driessche, Isabel Van; Hoste, Serge; Smedt, Stefaan De; Demeester, Joseph; Jain, Rahul; Ruddy, Shaun; Remon, Jean Paul

doi:10.1016/s0378-5173(01)00628-7

Cited by 106 publications

(37 citation statements)

References 8 publications

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“…In the field of pharmaceutical nanotechnology, SD has been used to isolation of nanoparticles (Vergote et al, 2001) or to produce amorphous nanoparticles (Chow and Sun, 2004). Dolenc et al (2009) reported on tableting of SD celecoxib nanoparticles, however assessed tablets comprised blends with microcrystalline cellulose.…”

Section: Graphical Abstractmentioning

confidence: 99%

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

Paluch¹,

Tajber²,

Adamczyk³

et al. 2012

International Journal of Pharmaceutics

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This work is made available online in accordance with publisher policies. Please refer to the repository record for this item and our Policy Document available from the repository home page for further information.To see the final version of this work please visit the publisher's website. Access to the published online version may require a subscription. AbstractHigh-dose API powders which are to be tableted by direct compression should have high compactibility and compressibility. This note reports on a novel approach to the manufacture of crystalline powders intended for direct compaction with improved compactibility and compressibility properties. The poorly compactable API, chlorothiazide, was spray dried from a water/acetone solvent mix producing additive-free nanocrystalline microparticles (NCMPs) of median particle size 3.5 µm. Tablets compacted from NCMPs had tensile strengths ranging from 0.5 to 4.6 MPa (compared to 0.6-0.9 MPa for tablets of micronised CTZ) at compression forces ranging from 6 kN to 13 kN. NCMP tablets also had high porosities (34-20%) and large specific surface areas (4.4 to 4.8 m 2 /g). The time taken for tablets made of NCMPs to erode was not statistically longer (p>0.05) than for tablets made of micronised CTZ. Fragmentation of NCMPs on compression was observed. The volume fraction of particles below 1 µm present in the suspension recovered after erosion of NCMP tablets was 34.8±3.43%, while no nanosized particles were detected in the slurry after erosion of compacted micronised CTZ.Keywords: spray drying, tabletability, specific surface area, nanocrystalline microparticles, erosion, This work presents SD/crystallisation of NCMPs composed of chlorothiazide (CTZ), a highdose API, previously shown to be crystalline when SD (Corrigan et al., 1984). The tabletability and erosion characteristics of NCMPs is assessed and compared to conventionally processed powders. 4 SD of CTZ (Sigma, Germany) samples using conditions as outlined in table 1 was performed using a Büchi B-290 Mini Spray Dryer (Büchi 93001 en). Tablets (n=10) were compressed using a MTCM 1 tablet press (GlobePharma, USA), supplied with concave 10 mm diameter tooling. Tablets (n=10) were subjected to hardness test using Dr. Schleuniger-6D tablet tester (Pharmatron, UK). Erosion studies were performed in a vertically held glass vial (7.5x2 cm), equipped on the bottom with a 2 mm wire mesh and a tubing pumping in and out erosion medium (15 ml of 0.1M HCl at 37 ˚C) at the flow rate of 30 ml/min. Erosion time was defined as the time when all tablet fragments have passed through the wire mesh. Obtained suspensions were introduced to wet laser diffraction particle size analysis performed in 0.1 M HCl using a Hydro µP attachment with no ultrasound, using the pump speed of 1000 rpm and initial obscuration of 20±2%. Solubility studies of CTZ in solvents were carried out in a shaking water bath at 50 rpm, for 24 hours in 25 ˚C. Excess of CTZ was loaded into 10 ml glass vials, suspended in 5 ml of the solvent and vials hermetically s...

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Section: Graphical Abstractmentioning

confidence: 99%

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

Paluch¹,

Tajber²,

Adamczyk³

et al. 2012

International Journal of Pharmaceutics

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“…Ketoprofen's short half-life in blood plasma (2-3 h), 6 coupled to its poor solubility in water, renders this NSAID a very good candidate for the formulation of controlled-release dosages. 7,8 The successful formulation of a stable and effective solid dosage form depends on the careful choice of the excipient. Lately, the use of hydrophilic polymers [e.g., cellulose derivatives, polyvinylpyrrolidone (PVP), either isolated or in blends] has attracted considerable attention, 10 due to their ability to form gels in an aqueous medium.…”

Section: Introductionmentioning

confidence: 99%

Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

2006

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Ketoprofen (3-benzoyl-a-methylbenzeneacetic acid) is a widely used nonsteroidal antiinflammatory drug (NSAID), always administered in the form of drug-excipient physical mixtures (PMs). The occurrence of possible interactions between ketoprofen and two commonly used excipients-lactose (LAC) and polyvinylpyrrolidone (PVP)-was evaluated, through vibrational spectroscopy techniques [both Raman and Inelastic Neutron Scattering (INS)]. Spectral evidence of drug:excipient close contacts, which were enhanced by aging, was verified for the (1:1) (w:w) (ketoprofen:PVP) and (ketoprofen:LAC) PMs, both by Raman and INS. These interactions were found to involve mainly the central carbonyl and the terminal methyl-carboxylic moieties of the ketoprofen molecule, this being reflected in particular vibrational modes, such as the methyl torsion, the outof-plane CÀ ÀOH bending, and the inter-ring C¼ ¼O stretching. #

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“…Ketoprofen shows incomplete release from sustain release formulation due to its low solubility. Vergote et al (2001) shows complete release of ketoprofen from sustains release formulation by loaded it in nano crystalline form 2,69 Various formulation approaches have been used to achieve sustain release, improvement in bioavailability, and decrease in side effect of gastric irritation of ketoprofen include preparation of matrix pellets of nano-crystalline ketoprofen, sustained release ketoprofen microparticles and formulations, floating oral ketoprofen systems, and transdermal systems of ketoprofen 70,71,72 Different problems like processing, stability and economic problem arises during preparation and stabilization of nanocrystalline or improved solubility forms of drug so by loading drug in SMEDDS such problems can be overcome. SMEDDS formulation enhances the bioavailability by increasing solubility of drug and also decreases the gastric irritation.…”

Section: Applicationsmentioning

confidence: 99%

Untitled

2012

IJPSR

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Oral route is the easiest and most convenient route of drug administration, being non invasive and cost effective, thereby leading worldwide drug delivery market. But major problem encountered in oral formulations (as estimated more than 50 % of oral formulations are found to be poorly aqueous soluble), is low bioavailability, giving rise to further problems like, high inter and intra subject variability, lack of dose uniformity and finally leading to therapeutic failure. The challenging task is to increase the bioavailability of drugs. Number of technological strategies are investigated and reported in literature for improving bioavailability like solid dispersions, cyclodextrins, micronization etc. But Self-microemulsifying Drug Delivery System (SMEDDS) have gained exposure for their ability to increase solubility and bioavailability of poorly aqueous soluble drugs with reduction in dose and also drugs are protected from hostile environment in gut. SMEDDS are isotropic mixture of oil, surfactant, drug and sometimes containing cosurfactant and administered orally which on mild agitation with GI fluids forms o/w microemulsion. This review gives complete overview of SMEDDS but special attention has been paid to formulation design, evaluation and little emphasis on application of SMEDDS.

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An oral controlled release matrix pellet formulation containing nanocrystalline ketoprofen

Cited by 106 publications

References 8 publications

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

A novel approach to crystallisation of nanodispersible microparticles by spray drying for improved tabletability

Drug–excipient interactions in ketoprofen: A vibrational spectroscopy study

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