Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers

Open access

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers

The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • A. R. Paradkar B. Chauhan S. Yamamura and A. P. Pawar Preparation and characterization of glassy celecoxib Drug Dev. Ind. Pharm.29 (2003) 739--744; DOI: 10.1081/DDC-120021773.

  • P. Gupta G. Chawala and A. K. Bansal Physical stability and solubility advantage from amorphous celecoxib: The role of thermodynamic quantities and molecular mobility Mol. Pharm.1 (2004) 406--413; DOI: 10.1021/mp049938f.

  • M. K. Gupta. A. Vanwert and R. H. Bogner Formation of physically stable amorphous drugs by milling with Neusilin J. Pharm. Sci.92 (2003) 536--551; DOI: 10.1002/jps.10308.

  • D. Q. Craig P. G. Royall V. L. Kett and M. L. Hopton The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems Int. J. Pharm.179 (1999) 179--207; DOI: 10.1016/S0378-5173(98)00338-X.

  • A. A. Ambike K. R. Mahadik A. R. Paradkar Stability study of amorphous valdecoxib Int. J. Pharm.282 (2004) 151--162; DOI: 10.1080/03639040500272025.

  • A. Paradkar M. Maheshwari R Kamble I. Grimsey and P. York Design and evaluation of celecoxib porous particles using melt sonocrystallization Pharm. Res.23 (2005) 1395--1400; DOI: 10.1007/s11095-006-0020-4.

  • D. Law S. L. Krill E. A. Schmitt J. J. Fort Y. H. Qiu W. L. Wang and W. R. Porter Physicochemical considerations in the preparation of amorphous ritonavir-poly(ethylene glycol) 8000 solid dispersions J. Pharm. Sci.90 (2001) 1015--1025; DOI: 10.1002/jps.1054.

  • H. Suzuki and H. Sunada Influence of water-soluble polymers on the dissolution of nifedipine solid dispersions with combined carriers Chem. Pharm. Bull.46 (1998) 482--487.

  • S. L. Shimpi B. Chauhan K. R. Mahadik and A. R. Paradkar Stabilization and improved in-vivo performance of amorphous etoricoxib using gelucier 50/13 Pharm. Res.22 (2005) 1727--1734; DOI: 10.1007/s11095-005-6694-1.

  • P. Gupta V. K. Kakamanu and A. K. Bansal Stability and solubility of celecoxib-PVP amorphous dispersions: molecular perspective Pharm. Res.21 (2004) 1762-1769; DOI:10.1023/B:PHAM. 0000045226.42859.b8.

  • P. Gupta R. Thilagavathi A. K. Chakraborti and A. K. Bansal Role of molecular interaction in stability of celecoxib-PVP amorphous systems Mol. Pharm.2 (2005) 384--391.

  • J. Akbuga A. Gursoy and F. Yetimoglu Preparation and properties of tablets prepared from furosemide-PVP solid dispersion systems Drug Dev. Ind. Pharm.14 (1988) 2091--2108.

  • K. R. Morris U. J. Griesserb C. J. Eckhardt and J. G. Stowell Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes Adv. Drug Deliv. Rev.48 (2001) 91--114; DOI: 10.1016/S0169-409X(01)00100-4.

  • T. Matsumoto N. Kaneniwa S. Higuchi and M. Otsuka Effects of temperature and pressure during compression on the polymorphic transformation and crushing strength of chlorpropamide tablets J. Pharm. Pharmacol.43 (1991) 74--78.

  • V. Andronis and G. Zografi The molecular mobility of supercooled amorphous indomethacin as a function of temperature and relative humidity Pharm. Res.15 (1998) 835--842.

  • M. Otsuka M. Nakanishi and Y. Matsuda. Effects of crystalline form on compression mechanism of phenobarbital polymorphs Drug Dev. Ind. Pharm.25 (1999) 205--215.

  • C. Lefebvre A. M. Guyot-Hermann M. Draguet-Bruchmans and R. Bouche Polymorphic transitions of carbamazepine during grinding and compression Drug Dev. Ind. Pharm.12 (1986) 1913--1927.

  • H. Chan and E. Doelker Polymorphic transformation of some drugs under compression Drug Dev. Ind. Pharm.11 (1985) 315--332.

  • A. G. Schmidt S. Wartewig and K. M. Picker Potential of carrageenan to protect drugs from polymorphic transformation Eur. J. Pharm. Biopharm.56 (2003) 101--110; DOI: 10.1016/S0939--6411(03)00037-7.

  • K. M. Picker "Soft tableting": A new concept to tablet pressure sensitive materials Pharm. Dev. Technol.9 (2004) 107--121; DOI: 10.1081/PDT-120027426.

  • United States Pharmacopoeia 24 National Formulary 19 USP Convention Rockville 2000.

Journal information
Impact Factor

IMPACT FACTOR 2018: 1.405
5-year IMPACT FACTOR: 1.701

CiteScore 2018: 1.47

SCImago Journal Rank (SJR) 2018: 0.314
Source Normalized Impact per Paper (SNIP) 2018: 0.637

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 311 187 11
PDF Downloads 139 92 7