New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs

Kim, Yong Il; Kim, Kyung Soo; Suh, Kwee Hyun; Shanmugam, Sumathi; Woo, Jong Soo; Yong, Chul Soon; Choi, Han Gon

doi:10.1016/j.ijpharm.2011.05.059

Cited by 31 publications

(16 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After that, tablets were withdrawn at these times to analyze properties such as color, water content, dissolution, assay etc. [12]. Table 2 shows blends of excipients and active drug were prepared and evaluated for the various parameters.…”

Section: Stability Studymentioning

confidence: 99%

See 1 more Smart Citation

Influence of poloxmer on the dissolution properties of mosapride and its pharmaceutical tablet formulation

2017

Egypt. J. Chem.

View full text Add to dashboard Cite

T HIS WORK was an attempt to improve therapeutic efficacy and increase patient compliance thereby formulating immediate release of Mosapride citrate's tablets with improved physical and chemical characteristics. The tablet form was prepared by wet granulation of Mosapride with a binder solution of Poloxmer 407 and compressed the dried granules of Mosapride into non-friable, stable tablets. The other objective, the performance of two classes of superdisintegrants as croscarmellose sodium (AcDi-Sol), and sodium starch glycolate (Primojel) in dissolution of Mosapride immediate release and promoting disintegration tablets was evaluated. The post-compression and the pre-compression parameters were characterized which within their respective standards must lie. Chemical composition and crystallinity were investigated via FTIR and XRD, respectively. The post compression parameters such as thickness test, hardness, friability testes and in vitro drug release studies were also performed.

show abstract

Section: Stability Studymentioning

confidence: 99%

“…Thermodynamic activity is higher in the amorphous form of the drug than its crystalline form, leading to improve the solubility [12]. Similarly, such improving was due to the change of crystallinity to the amorphous form in the Mosapride-loaded solid dispersion.…”

Section: X-ray Diffraction Analysismentioning

confidence: 99%

Influence of poloxmer on the dissolution properties of mosapride and its pharmaceutical tablet formulation

2017

Egypt. J. Chem.

View full text Add to dashboard Cite

show abstract

“…The authors present the results of a 4 week multi-center, prospective, open-label, randomized trial aiming to assess the antiplatelet efficacy and tolerability of a clopidogrel napadisilate (CN) generic formulation compared with clopidogrel bisulfate (CB). The CN salt contains 2-naphthalene-sulfonic acid monohydrate, instead of bisulfate and it is optically pure and more stable against moisture and heat than clopidogrel hydrogen sulfate 20 . The participants of the study were patients (men and women) aged between 20 and 85 years who had undergone PCI with a drug-eluting stent (DES) placement for 43 months before enrolment.…”

mentioning

confidence: 99%

Evaluating the bioequivalence of clopidogrel generic formulations

Tsoumani

Ntalas

Goudevenos

et al. 2015

Current Medical Research and Opinion

View full text Add to dashboard Cite

“…Among the various approaches to improve the solubility and dissolution of poorly water-soluble drugs, the solid dispersion method appears to be the most successful as it is simple and economical. 4) This technique is a favored technique to increase the aqueous solubility of poorly watersoluble drugs by dispersing the drug in a hydrophilic carrier via solvent evaporation, solvent wetting or melting methods. 4,5) However, in these methods, there are some limitations with the choice of drug and formulation dose, and the high temperature of the melting method may affect the stability of the active ingredient of the formulation.…”

mentioning

confidence: 99%

“…4) This technique is a favored technique to increase the aqueous solubility of poorly watersoluble drugs by dispersing the drug in a hydrophilic carrier via solvent evaporation, solvent wetting or melting methods. 4,5) However, in these methods, there are some limitations with the choice of drug and formulation dose, and the high temperature of the melting method may affect the stability of the active ingredient of the formulation. 5) Moreover, the solvent evaporation and wetting methods may lead to unstable formulations as they will change the crystalline drug into an amorphous form.…”

mentioning

confidence: 99%

Clopidogrel Napadisilate Monohydrate Loaded Surface-Modified Solid Dispersion: Physicochemical Characterization and <i>in Vivo</i> Evaluation

Kim

Kwon

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

To develop a novel solid dispersion of clopidogrel napadisilate monohydrate (CNM) with improved stability and oral bioavailability, surface-modified solid dispersions were prepared by spray-drying using water as a solvent, Tween 80 as a surfactant, and hydroxypropylmethyl cellulose (HPMC) as a hydrophilic polymer, and optimized according to drug solubility. Its solid-state characterization was evaluated by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The stability study was performed at 50°C/75% RH over a period of 6 weeks. Its dissolution profiles and oral bioavailability in rats were also compared with that of CNM and clopidogrel bisulfate (CB). The solid dispersion, composed of CNM/HPMC/Tween80 at a weight ratio of 10/2.5/2.5, in which CNM was in the crystalline state, increased the drug solubility approximately 4.6-fold. It showed a significantly better dissolution profile than that of CNM in all the dissolution media, and gave either similar or higher dissolution compared to that of CB. This solubility and dissolution enhancement was attributed to improved wetting and solubilization of CNM crystals due to hydrophilic carriers attached on the drug surface. It had excellent stability, thereby addressing the stability problem of CB powder. Furthermore, it increased the area under curve (AUC) values by about 4-fold and 1.6-fold compared to CNM and CB, respectively, suggesting that it improved the oral bioavailability of the drug in rats. Thus, this solid dispersion system prepared with water, HPMC and Tween 80 can be used to enhance the bioavailability of CNM as well as to solve the stability problem of CB.Key words clopidogrel napadisilate monohydrate; surface-modified solid dispersion; water; stability; bioavailability Clopidogrel, a non-competitive inhibitor of adenosine diphosphate in platelets is an orally administered antiplatelet agent prescribed for cerebral and peripheral vascular diseases and for the early and long term secondary prevention of atherothrombotic events in patients with acute coronary syndromes.1) This drug is practically insoluble in water; hence, its commercial salt form, clopidogrel bisulfate (CB) has been widely used in the pharmaceutical industry. CB is highly soluble in water and rapidly absorbed in vivo; however, this salt form is slightly hygroscopic and has been reported not stable under accelerated heat and moisture conditions, producing severe amounts of degradants.2) Thus, to increase the stability of the drug, a new salt form, clopidogrel napadisilate monohydrate (CNM), has been prepared with improved stability.3) Even though CNM demonstrated increased stability, this salt showed poor aqueous solubility compared to the CB salt.3) Therefore, a novel formulation strategy is needed to resolve the solubility issue of stable CNM.Drug solubility remains one of the most challenging aspects of formulation development because it results in poor bioavailability of the drug. Among the various approaches to improve the ...

show abstract

New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs

Cited by 31 publications

References 34 publications

Influence of poloxmer on the dissolution properties of mosapride and its pharmaceutical tablet formulation

Influence of poloxmer on the dissolution properties of mosapride and its pharmaceutical tablet formulation

Evaluating the bioequivalence of clopidogrel generic formulations

Clopidogrel Napadisilate Monohydrate Loaded Surface-Modified Solid Dispersion: Physicochemical Characterization and <i>in Vivo</i> Evaluation

Contact Info

Product

Resources

About