Skip to main content
SpringerLink
Log in

Evaluation of carvedilol compatibility with lipid excipients for the development of lipid-based drug delivery systems

  • Published:
Journal of Thermal Analysis and Calorimetry Aims and scope Submit manuscript

Abstract

Carvedilol (CARV) is a widely used non-selective β-blocker, which has shown low bioavailability after oral administration (20 %) due to its low water solubility and intense first-pass metabolism. Lipid-based drug delivery systems have been proposed to improve CARV oral bioavailability. An evaluation of drug–excipient compatibility is needed to clarify potential physical and chemical interactions between them and therefore guarantee a correct selection of excipients. However, to date there are no reports on the systematic evaluation of CARV–lipid excipient compatibility. Thus, the aim of this study was to evaluate the compatibility of CARV with the lipid excipients commonly used for the development of lipid-based formulations. Thermal analysis techniques (DTA and TG/DTG), Fourier transform infrared spectroscopy and isothermal stress testing (IST) were used for this purpose. The results of this study showed that 4 of the 10 lipid excipients studied were incompatible with CARV. The strongest thermal and spectroscopic modifications were observed in CARV mixtures with oleic acid, lauric acid, lauroyl polyoxylglycerides (Gelucire® 44/14) and glyceryl caprylate/caprate (Capmul® MCM). In addition, these mixtures resulted in significant decreases in drug content after aging. On the other hand, palmitic acid, stearic acid, glyceryl behenate (Compritol ATO® 188), tribeheninPEG (Emulium® 22), polyglyceryl-6-isostearate (Plurol Isostearique®) and diethylene glycol monoethyl ether (Transcutol HP®) were considered good candidates for developing self-emulsifying drug delivery systems and for preparing lipid microparticle or nanoparticle containing CARV. These findings denote the relevance of combining thermal and spectroscopic techniques with thermal stress testing for the accurate determination of drug–lipid excipient compatibility.

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

  1. Chakraborty S, Shukla D, Jain A, Mishra B, Singh S. Assessment of solubilization characteristics of different surfactants for carvedilol phosphate as a function of pH. J Colloid Interface Sci. 2009;335(2):242–9.

    Article  CAS  Google Scholar 

  2. Dantas EM, Pimentel EB, Andreao RV, Cichoni BS, Goncalves CP, Zaniqueli Ddos A, et al. Carvedilol recovers normal blood pressure variability in rats with myocardial infarction. Auton Neurosci. 2013;177(2):231–6.

    Article  CAS  Google Scholar 

  3. Venishetty VK, Chede R, Komuravelli R, Adepu L, Sistla R, Diwan PV. Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: a novel strategy to avoid intraduodenal administration. Colloid Surf B. 2012;95:1–9.

    Article  CAS  Google Scholar 

  4. Planinšek O, Kovačič B, Vrečer F. Carvedilol dissolution improvement by preparation of solid dispersions with porous silica. Int J Pharm. 2011;406(1–2):41–8.

    Article  Google Scholar 

  5. Benet LZ. The role of BCS (biopharmaceutics classification system) and BDDCS (biopharmaceutics drug disposition classification system) in drug development. J Pharm Sci. 2013;102(1):34–42.

    Article  CAS  Google Scholar 

  6. Singh B, Singh R, Bandyopadhyay S, Kapil R, Garg B. Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol. Colloid Surf B. 2013;101:465–74.

    Article  CAS  Google Scholar 

  7. Chakraborty S, Shukla D, Vuddanda PR, Mishra B, Singh S. Effective in vivo utilization of lipid-based nanoparticles as drug carrier for carvedilol phosphate. J Pharm Pharmacol. 2011;63(6):774–9.

    Article  CAS  Google Scholar 

  8. Shamma RN, Basha M. Soluplus®: a novel polymeric solubilizer for optimization of Carvedilol solid dispersions: formulation design and effect of method of preparation. Powder Technol. 2013;237:406–14.

    Article  CAS  Google Scholar 

  9. Yuvaraja K, Khanam J. Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid. J Pharm Biomed Anal. 2014;96:10–20.

    Article  CAS  Google Scholar 

  10. Zhang Y, Zhi Z, Li X, Gao J, Song Y. Carboxylated mesoporous carbon microparticles as new approach to improve the oral bioavailability of poorly water-soluble carvedilol. Int J Pharm. 2013;454(1):403–11.

    Article  CAS  Google Scholar 

  11. Kalepu S, Manthina M, Padavala V. Oral lipid-based drug delivery systems—an overview. Acta Pharm Sin. 2013;3(6):361–72.

    Article  Google Scholar 

  12. Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Deliv Rev. 2008;60(6):625–37.

    Article  CAS  Google Scholar 

  13. Shah MK, Madan P, Lin S. Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration. Pharm Dev Technol. 2014;19(4):475–85.

    Article  CAS  Google Scholar 

  14. Chakraborty S, Shukla D, Mishra B, Singh S. Lipid—an emerging platform for oral delivery of drugs with poor bioavailability. Eur J Pharm Biopharm. 2009;73(1):1–15.

    Article  CAS  Google Scholar 

  15. Rao S, Tan A, Thomas N, Prestidge CA. Perspective and potential of oral lipid-based delivery to optimize pharmacological therapies against cardiovascular diseases. J Control Release. 2014;193:174–87.

    Article  CAS  Google Scholar 

  16. Kuentz M. Lipid-based formulations for oral delivery of lipophilic drugs. Drug Discov Today Technol. 2012;9(2):e97–104.

    Article  CAS  Google Scholar 

  17. Wei L, Sun P, Nie S, Pan W. Preparation and evaluation of SEDDS and SMEDDS containing carvedilol. Drug Dev Ind Pharm. 2005;31(8):785–94.

    Article  CAS  Google Scholar 

  18. Salimi A, Sharif Makhmal Zadeh B, Hemati AA, Akbari Birgani S. Design and evaluation of self-emulsifying drug delivery system (SEDDS) of carvedilol to improve the oral absorption. Jundishapur J Nat Pharm Prod. 2014;9(3):e16125.

    Article  Google Scholar 

  19. Wei L, Li J, Guo L, Nie S, Pan W, Sun P, et al. Investigations of a novel self-emulsifying osmotic pump tablet containing carvedilol. Drug Dev Ind Pharm. 2007;33(9):990–8.

    Article  CAS  Google Scholar 

  20. Rao MRP, Munjapara GS, Khole IA. Preparation and evaluation of self-microemulsifying drug delivery system of carvedilol. Lat Am J Pharm. 2011;30(5):837–43.

    CAS  Google Scholar 

  21. Mahmoud EA, Bendas ER, Mohamed MI. Preparation and evaluation of self-nanoemulsifying tablets of carvedilol. AAPS PharmSciTech. 2009;10(1):183–92.

    Article  CAS  Google Scholar 

  22. Mahmoud E, Bendas E, Mohamed M. Effect of formulation parameters on the preparation of superporous hydrogel self-nanoemulsifying drug delivery system (SNEDDS) of carvedilol. AAPS PharmSciTech. 2010;11(1):221–5.

    Article  CAS  Google Scholar 

  23. Chakraborty S, Shukla D, Vuddanda PR, Mishra B, Singh S. Utilization of adsorption technique in the development of oral delivery system of lipid based nanoparticles. Colloid Surf B. 2010;81(2):563–9.

    Article  CAS  Google Scholar 

  24. Sanjula B, Shah FM, Javed A, Alka A. Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement. J Drug Target. 2009;17(3):249–56.

    Article  CAS  Google Scholar 

  25. Saindane N, Pagar K, Vavia P. Nanosuspension based in situ gelling nasal spray of carvedilol: development, in vitro and in vivo characterization. AAPS PharmSciTech. 2013;14(1):189–99.

    Article  CAS  Google Scholar 

  26. Kuo Y-C, Chung C-Y. Solid lipid nanoparticles comprising internal Compritol 888 ATO, tripalmitin and cacao butter for encapsulating and releasing stavudine, delavirdine and saquinavir. Colloid Surf B. 2011;88(2):682–90.

    Article  CAS  Google Scholar 

  27. Patil H, Feng X, Ye X, Majumdar S, Repka M. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach. AAPS J. 2015;17(1):194–205.

    Article  CAS  Google Scholar 

  28. Vithani K, Cuppok Y, Mostafa S, Slipper IJ, Snowden MJ, Douroumis D. Diclofenac sodium sustained release hot melt extruded lipid matrices. Pharm Dev Technol. 2014;19(5):531–8.

    Article  CAS  Google Scholar 

  29. Singh B, Khurana L, Bandyopadhyay S, Kapil R, Katare OO. Development of optimized self-nano-emulsifying drug delivery systems (SNEDDS) of carvedilol with enhanced bioavailability potential. Drug Deliv. 2011;18(8):599–612.

    Article  CAS  Google Scholar 

  30. de Barros Lima Í, Lima NB, Barros DC, Oliveira T, Mendonça CS, Barbosa E, et al. Compatibility study between hydroquinone and the excipients used in semi-solid pharmaceutical forms by thermal and non-thermal techniques. J Therm Anal Calorim. 2015;120(1):719–32.

    Article  Google Scholar 

  31. Kumar N, Bansal R, Bansal G. Evaluation of compatibility of itraconazole with excipients used to develop vesicular colloidal carriers. J Therm Anal Calorim. 2014;115(3):2415–22.

    Article  CAS  Google Scholar 

  32. Borba P, Vecchia D, Riekes M, Pereira R, Tagliari M, Silva M, et al. Pharmaceutical approaches involving carvedilol characterization, compatibility with different excipients and kinetic studies. J Therm Anal Calorim. 2014;115(3):2507–15.

    Article  CAS  Google Scholar 

  33. Kumar N, Goindi S, Saini B, Bansal G. Thermal characterization and compatibility studies of itraconazole and excipients for development of solid lipid nanoparticles. J Therm Anal Calorim. 2014;115(3):2375–83.

    Article  CAS  Google Scholar 

  34. Shete H, Patravale V. Long chain lipid based tamoxifen NLC. Part I: preformulation studies, formulation development and physicochemical characterization. Int J Pharm. 2013;454(1):573–83.

    Article  CAS  Google Scholar 

  35. Beg S, Jena SS, Patra CN, Rizwan M, Swain S, Sruti J, et al. Development of solid self-nanoemulsifying granules (SSNEGs) of ondansetron hydrochloride with enhanced bioavailability potential. Colloid Surf B. 2013;101:414–23.

    Article  CAS  Google Scholar 

  36. Chadha R, Bhandari S. Drug–excipient compatibility screening—role of thermoanalytical and spectroscopic techniques. J Pharm Bio Anal. 2014;87:82–97.

    Article  CAS  Google Scholar 

  37. Kasongo KW, Pardeike J, Muller RH, Walker RB. Selection and characterization of suitable lipid excipients for use in the manufacture of didanosine-loaded solid lipid nanoparticles and nanostructured lipid carriers. J Pharm Sci. 2011;100(12):5185–96.

    Article  CAS  Google Scholar 

  38. Patil-Gadhe A, Pokharkar V. Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement. Eur J Pharm Biopharm. 2014;88(1):160–8.

    Article  CAS  Google Scholar 

  39. Talvani A, Bahia M, Sá-Barreto L, Lima E, Cunha-Filho M. Carvedilol: decomposition kinetics and compatibility with pharmaceutical excipients. J Therm Anal Calorim. 2014;115(3):2501–6.

    Article  CAS  Google Scholar 

  40. Borhade V, Pathak S, Sharma S, Patravale V. Clotrimazole nanoemulsion for malaria chemotherapy. Part I: preformulation studies, formulation design and physicochemical evaluation. Int J Pharm. 2012;431(1–2):138–48.

    Article  CAS  Google Scholar 

  41. Hokama N, Hobara N, Kameya H, Ohshiro S, Sakanashi M. Rapid and simple micro-determination of carvedilol in rat plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1999;732(1):233–8.

    Article  CAS  Google Scholar 

  42. Solís-Fuentes JA, Durán-de-Bazúa C. Characterization of eutectic mixtures in different natural fat blends by thermal analysis. Eur J Lipid Sci Technol. 2003;105(12):742–8.

    Article  Google Scholar 

  43. Zhang N, Yuan Y, Yuan Y, Li T, Cao X. Lauric–palmitic–stearic acid/expanded perlite composite as form-stable phase change material: preparation and thermal properties. Energy Build. 2014;82:505–11.

    Article  Google Scholar 

  44. Sharma A, Jain CP. Preparation and characterization of solid dispersions of carvedilol with PVP K30. Res Pharm Sci. 2010;5(1):49–56.

    CAS  Google Scholar 

  45. Stott PW, Williams AC, Barry BW. Mechanistic study into the enhanced transdermal permeation of a model β-blocker, propranolol, by fatty acids: a melting point depression effect. Int J Pharm. 2001;219(1–2):161–76.

    Article  CAS  Google Scholar 

  46. Misic Z, Jung DS, Sydow G, Kuentz M. Understanding the interactions of oleic acid with basic drugs in solid lipids on different biopharmaceutical levels. J Excip Food Chem. 2014;5(2):113–34.

    Google Scholar 

  47. Cides LCS, Araújo AAS, Santos-Filho M, Matos JR. Thermal behaviour, compatibility study and decomposition kinetics of glimepiride under isothermal and non-isothermal conditions. J Therm Anal Calorim. 2006;84(2):441–5.

    Article  CAS  Google Scholar 

  48. Maximiano F, Novack K, Bahia M, de Sá-Barreto L, da Cunha-Filho M. Polymorphic screen and drug–excipient compatibility studies of the antichagasic benznidazole. J Therm Anal Calorim. 2011;106(3):819–24.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa no Estado de Goiás (FAPEG) for their financial support and Chengtai Shenyang Fine Chemical Factory and IQUEGO (Indústria Química do Estado de Goiás) for providing carvedilol.

Author information

Authors and Affiliations

  1. Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, GO, Brazil

    Luís Antônio Dantas Silva, Fernanda Vieira Teixeira, Raphael Caixeta Serpa, Najla Locatelli Esteves, Rayane Ramos dos Santos, Eliana Martins Lima, Stephânia Fleury Taveira & Ricardo Neves Marreto

  2. Laboratory of Food, Drug and Cosmetics (LTMAC), School of Health Sciences, University of Brasília, Brasília, DF, 70910-900, Brazil

    Marcílio Sérgio Soares da Cunha-Filho

  3. Department of Pharmacy, Federal University of Sergipe, São Cristóvão, SE, Brazil

    Adriano Antunes de Souza Araújo

  4. Faculdade de Farmácia, Universidade Federal de Goiás (UFG), Avenida Universitária, Setor Universitário, s/n, Goiânia, GO, 74605-220, Brazil

    Ricardo Neves Marreto

Authors
  1. Luís Antônio Dantas Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernanda Vieira Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raphael Caixeta Serpa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Najla Locatelli Esteves
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rayane Ramos dos Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eliana Martins Lima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marcílio Sérgio Soares da Cunha-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adriano Antunes de Souza Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stephânia Fleury Taveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ricardo Neves Marreto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ricardo Neves Marreto.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Silva, L.A.D., Teixeira, F.V., Serpa, R.C. et al. Evaluation of carvedilol compatibility with lipid excipients for the development of lipid-based drug delivery systems. J Therm Anal Calorim 123, 2337–2344 (2016). https://doi.org/10.1007/s10973-015-5022-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10973-015-5022-1

Keywords

Search

Navigation