Skip to main content
SpringerLink
Log in

Preparation of amorphous carvedilol polymeric microparticles for improvement of physicochemical properties

  • Research Article
  • Published:
Journal of Pharmaceutical Investigation Aims and scope Submit manuscript

Abstract

The aim of the present study was to enhance the physicochemical properties of poorly aqueous soluble carvedilol (CRV) by preparing its microparticles in presence and/or in absence of a hydrophilic carrier. The polymeric microparticles of CRV were prepared with polyvinylpyrrolidone K30 with or without addition of adsorbents like Aerosil®200 and/or Sylysia®350 by using spray drying technique. The dissolution profiles revealed that the drug and polymer ratio and colloidal silica both played critical role in solubility enhancement. The spray dried microparticles and drug alone were characterized by differential scanning calorimetry (DSC), X-ray powder diffraction, Fourier transformation infrared spectroscopy (FTIR), particle size analysis and scanning electron microscopy (SEM). DSC analysis showed that CRV transformed from the crystalline state to amorphous state by spray drying, confirmed by disappearance of its melting peak. The results of the X-ray analysis were in agreement with the thermal analysis data. It did not show characteristic crystalline drug peaks which confirmed that the amorphous form of CRV was present in the CRV loaded microparticles. FTIR analysis demonstrated hydrogen bonding interaction with an absence of significant chemical interaction between CRV and polymer. Spherical microparticles were yielded with smooth surfaces as observed by SEM. All in all, this work reveals that spray drying is a suitable technique for preparation of microparticles with improved physicochemical properties of CRV.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Ambike AA, Mahadik KR, Paradkar A (2004) Stability study of amorphous valdecoxib. Int J Pharm 282:151–162

    Article  PubMed  CAS  Google Scholar 

  • Bhise S, Mathure D, Mithun VK, Patankar RD (2011) Solubility enhancement of antihypertensive agent by solid dispersion technique. Int J Pharm Life Sci 2:970–975

    CAS  Google Scholar 

  • Borut K, Franc VE, Odon PE (2011) Solid dispersions of carvedilol with porous silica. Chem Pharm Bull 59:427–433

    Article  Google Scholar 

  • Chauhan B, Shimpi S, Paradkar A (2005) Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci 26:219–230

    Article  PubMed  CAS  Google Scholar 

  • Higuchi T, Connors KA (1965) Phase-solubility techniques. Adv Anal Chem Instrum 4:117–212

    CAS  Google Scholar 

  • Jain H, Gediya S, Sutariya V, Shah H (2011) Biopharmaceutical classification system: a review. IJPI J Pharm Cosmetol 1:106–117

    Google Scholar 

  • Kini AG, Dixit M, Kulkarni PK (2011) Enhancement of solubility and dissolution rate of poorly water soluble drug by spray drying using different grade of chitosan. Int J Pharm Pharm Sci 3:231–235

    CAS  Google Scholar 

  • Kristmundsdottir T, Gudmundsson OS, Ingvarsdottir K (1996) Release of diltiazem from Eudragit microparticles prepared by spray-drying. Int J Pharm 137:159–165

    Article  CAS  Google Scholar 

  • Kumar RH, Bandari S, Jukanti R, Veerareddy PR (2011) Solubility enhancement and physicochemical characterization of carvedilol solid dispersion with gelucire 50/13. Arch Pharmacal Res 34:51–57

    Article  Google Scholar 

  • Lin S, Hsu C, Ke W (2010) Solid-state transformation of different gabapentin polymorphs upon milling and co-milling. Int J Pharm 396:83–90

    Article  PubMed  CAS  Google Scholar 

  • Lipinski CA, Franco L, Beryl WD, Paul JF (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Del 46:3–26

    Article  CAS  Google Scholar 

  • Nanda GS, Mitali K, Lin L, Zaher J (2010) Fabrication of composite microparticles of artemisinin for dissolution enhancement. Powder Technol 203:277–287

    Article  Google Scholar 

  • Nanda GS, Mitali K, Lin L, Zaher J, Rainer HM (2011) Dissolution enhancement of a poorly water-soluble antimalarial drug by means of a modified multi-fluid nozzle pilot spray drier. Mater Sci Eng C 31:391–399

    Article  Google Scholar 

  • Noyes AA, Whitney WR (1897) The rate of solution of solid substances in their own solutions. J Am Chem Soc 19:930–934

    Article  Google Scholar 

  • Odon PS, Borut KC, Franc V (2011) Carvedilol dissolution improvement by preparation of solid dispersions with porous silica. Int J Pharm 406:41–48

    Article  Google Scholar 

  • Pandya VM, Patel DJ, Patel JK, Patel RP (2009) Formulation, characterization, and optimization of fast-dissolve tablets containing celecoxib solid dispersion. DissoTechnol 16(4):22–27

    CAS  Google Scholar 

  • Pardhi DM, Shivhare UD, Mathur VB, Bhusari KP (2010) Liquisolid technique for enhancement of dissolution properties of carvedilol. Der Pharm Lett 2:412–427

    CAS  Google Scholar 

  • Patel RP, Patel MP, Suthar AM, Baria AH (2009) Formulation and process optimization of solid dispersion of meloxicam and PEG 8000 prepared by spray drying. Int J Pharm Sci Nanotech 2:647–653

    CAS  Google Scholar 

  • Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik KR, Paradkar A (2006) Development, characterization and stabilization of amorphous form of a low TG drug. Powder Technol 167:20–25

    Article  CAS  Google Scholar 

  • Prajapati RK, Mahajan HS, Surana SJ (2011) PLGA based mucoadhesive microspheres for nasal delivery: in vitro/ex vivo studies. Indian J Nov Drug Deliv 3:9–16

    Google Scholar 

  • Rattes AL, Oliveira WP (2007) Spray drying conditions and encapsulating composition effects on formation and properties of sodium diclofenac microparticles. Powder Technol 171:7–14

    Article  CAS  Google Scholar 

  • Riekes MK, Barboza FM, Vecchia DD, Bohatch M, Farago PV, Fernandes D, Segatto Silva MA, Stulzer HK (2011) Evaluation of oral carvedilol microparticles prepared by simple emulsion technique using poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and polycaprolactone as polymers. Mater Sci Eng C 31:962–968

    Article  CAS  Google Scholar 

  • Rogers TL, Overhoff KA, Shah P, Santiago P, Yacaman MJ, Johnson KP (2003) Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process. Eur J Pharm Biopharm 55:161–172

    Article  PubMed  CAS  Google Scholar 

  • Roni AM, Dipu HM, Kibria G, Rahman H, Rony RM (2011) Dissolution enhancement of poorly soluble carbamazepine by using polymeric solid dispersions. Int J Pharm Sci Res 2:49–57

    Google Scholar 

  • Rowe RC, Sheskey PJ, Owen SC (1994) Handbook of pharmaceutical excipients, 5th edn. The Pharmaceutical Press, and the American Pharmacists Association, Washington, DC, pp 611–616

    Google Scholar 

  • Sammour OA, Hammad MA, Megrab NA, Zidan AS (2006) Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion. AAPS Pharm Sci Tech 7(2):E1–E9

    Article  Google Scholar 

  • Sharma A, Jain CP (2010) Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci 5:49–56

    PubMed  CAS  Google Scholar 

  • Shinde SS, Patil SS, Mevekari FI, Satpute AS (2010) An approach for solubility enhancement: solid dispersion. Int J Adv Pharm Sci 1:299–308

    CAS  Google Scholar 

  • Silva-Junior AA, Matos JR, Formariza PT, Rossanezi G, Scarpa VM, Eryvaldo SE, Oliveira AG (2009) Thermal behavior and stability of biodegradable spray-dried microparticles containing triamcinolone. Int J Pharm 368:45–55

    Article  Google Scholar 

  • Silverstein RM, Webster FX (2010) Spectrometric identification of organic compounds, 6th edn. Wiley, New York, pp 136–140 (Authorized reprint by Wiley India of Edition)

  • Takeuchi H, Nagira S, Yamamoto H, Kawashima Y (2004) Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying method. Powder Technol 141:187–195

    Article  CAS  Google Scholar 

  • Takeuchi H, Nagira S, Yamamoto H, Kawashima Y (2005) Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method. Int J Pharm 293:155–164

    Article  PubMed  CAS  Google Scholar 

  • Tapas AR, Kawtikwar PS, Sakarkar DM (2012) Preparation of carvedilol spherical crystals having solid dispersion structure by the emulsion solvent diffusion method and evaluation of its in vitro characteristics. In: Mastai Y (ed) Advances in Crystallization Processes, pp 633–648. ISBN:978-953-51-0581-7

  • Thorsteinn L, Stine BV, Cyrielle D, Phatsawee J (2008) Carvedilol: solubilization and cyclodextrin complexation: a technical note. AAPS Pharm Sci Tech 9:425–430

    Article  Google Scholar 

  • Waghmare A, Pore Y, Kuchekar B (2008) Development and characterization of zaleplon solid dispersion systems: a technical note. AAPS Pharm Sci Tech 9(2):536–543

    Article  CAS  Google Scholar 

  • Yanchen H, Zhuangzhi Z, Wang T, Jiang T, Wanga S (2011) Incorporation of indomethacin nanoparticles into 3-D ordered macroporous silica for enhanced dissolution and reduced gastric irritancy. Eur J Pharm Biopharm 79:544–551

    Article  Google Scholar 

  • Yanchen H, Zhuangzhi Z, Qinfu Z, Chao W, Peng Z, Haitao J, Siling W (2012) 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Microporous Mesoporous Mater 147:94–101

    Article  Google Scholar 

  • Zhaoa Q, Wang T, Wang J, Zheng L, Jiang T, Cheng G, Wang S (2011) Template-directed hydrothermal synthesis of hydroxyapatite as a drug delivery system for the poorly water-soluble drug carvedilol. Appl Surf Sci 257:10126–10133

    Article  Google Scholar 

Download references

Acknowledgments

Authors are very much grateful to Symed Labs Hyderabad, India for providing gift samples of pure drug CRV. Authors are thankful to Signet Chem. Lab, Mumbai, India for providing PVP K30 for this research work. Authors are also thankful to Degussa Evonik, Mumbai, India and Fuji Silysia Chemical Ltd., Japan for providing gift samples of Aerosil® 200 and Sylysia® 350 respectively. The authors are thankful to Shivaji University, Kolhapur and Pune University, Pune, Maharashtra, India for providing analytical facilities. All authors express their sincere gratitude towards Principal, Govt. College of Pharmacy, Karad, Maharashtra, India for providing laboratory facilities and constant encouragement.

Author information

Authors and Affiliations

  1. Department of Biopharmaceutics, Government College of Pharmacy, Karad, Maharashtra, 415124, India

    Priyanka Bhosale & Fahim Sayyad

  2. Department of Pharmaceutical Chemistry, Government College of Pharmacy, Karad, Maharashtra, 415124, India

    Yogesh Pore

Authors
  1. Priyanka Bhosale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yogesh Pore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fahim Sayyad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yogesh Pore.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bhosale, P., Pore, Y. & Sayyad, F. Preparation of amorphous carvedilol polymeric microparticles for improvement of physicochemical properties. Journal of Pharmaceutical Investigation 42, 335–344 (2012). https://doi.org/10.1007/s40005-012-0046-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40005-012-0046-z

Keywords

Search

Navigation