Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50 cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.

Original languageEnglish
Pages (from-to)674-683
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume70
Issue number2
DOIs
Publication statusPublished - 10-2008

Fingerprint

Tablets
Pharmacokinetics
Pharmaceutical Preparations
Porosity
Methylene Chloride
Differential Scanning Calorimetry
Acetone
Crystallization
In Vitro Techniques
Clinical Studies
aceclofenac
Particle Size
X-Ray Diffraction
Electron Scanning Microscopy
Solubility
Spectrum Analysis
Polymers
Water

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Cite this

@article{b7d82f7dd86440378b7e8228158c06a8,
title = "Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates",
abstract = "Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50 cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.",
author = "Usha, {Achutha Nayak} and Srinivas Mutalik and Reddy, {Meka Sreenivasa} and Ranjith, {Averineni Kumar} and Pralhad Kushtagi and Nayanabhirama Udupa",
year = "2008",
month = "10",
doi = "10.1016/j.ejpb.2008.06.010",
language = "English",
volume = "70",
pages = "674--683",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Preparation and, in vitro, preclinical and clinical studies of aceclofenac spherical agglomerates

AU - Usha, Achutha Nayak

AU - Mutalik, Srinivas

AU - Reddy, Meka Sreenivasa

AU - Ranjith, Averineni Kumar

AU - Kushtagi, Pralhad

AU - Udupa, Nayanabhirama

PY - 2008/10

Y1 - 2008/10

N2 - Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50 cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.

AB - Aceclofenac agglomerates were prepared by spherical crystallization technique using a three solvent system comprising acetone: dichloromethane (DCM): water (bridging liquid, good solvent and bad solvent, respectively). Hydroxypropyl methylcellulose-50 cps (HPMC) in different concentrations was used as hydrophilic polymer. The effect of speed of rotation and amount of bridging liquid on spherical agglomeration were studied. The agglomerates were subjected to various physicochemical evaluations such as practical yield, drug content, particle size, loss on drying, porosity, IR spectroscopy, differential scanning calorimetry, X-ray diffraction studies, relative crystallinity, scanning electron microscopy, micromeritic properties, solubility and dissolution studies. The agglomerates showed improved micromeritic properties as well as dissolution behaviour in comparison to conventional drug crystals. The optimized agglomerates (F-9) showed good sphericity as well as high drug release, and hence they were compressed into tablets by direct compression. The tablets were found within the limits with respect to various physicochemical parameters. The dissolution rate of prepared tablets was better than that of marketed tablet and pure drug. The optimized agglomerates and tablet formulations were found to be stable for 6 months under accelerated conditions. The in vivo studies (preclinical pharmacokinetics, pharmacodynamics and toxicity studies, and clinical pharmacokinetics) of optimized agglomerates were carried out. The results of preclinical studies revealed that the agglomerates provided improved pharmacodynamic and pharmacokinetic profiles of drug besides being nontoxic. The results of pharmacokinetic studies of optimized tablet in human subjects indicated improved pharmacokinetic parameters of drug in comparison with that of marketed tablet.

UR - http://www.scopus.com/inward/record.url?scp=52949121078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=52949121078&partnerID=8YFLogxK

U2 - 10.1016/j.ejpb.2008.06.010

DO - 10.1016/j.ejpb.2008.06.010

M3 - Article

VL - 70

SP - 674

EP - 683

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 2

ER -