Influence of excipients on mixtures containing high amount of dry extract from Aesculus hippocastanum L.

Soares, L A L;
Costa, L;
Ferreira, M;
Souza, , T.

Luiz Alberto Lira Soares

Laboratório de Farmacognosia - Departamento de Ciências Farmacêuticas – UFPE Rua Prof. Artur de Sá, s/n; Cidade Universitária; Recife-PE; CEP: 50740-521 Tel.: +55 81 30764774; Fax: +55 812126-8510

raduado em Farmácia pela Universidade Federal de Pernambuco (1994), possui mestrado (1997) e doutorado em Ciências Farmacêuticas pela Universidade Federal do Rio Grande do Sul (2002). Bolsista CAPES-DAAD no Departamento de Tecnologia Farmacêutica - Eberhard Karls Universität, Tübingen (2000-2001), . Atuou como Professor Adjunto do Departamento de Farmácia da UFRN (JUL/2002-DEZ/2008), vice-coordenador do PPGCF-UFRN (2005-2008) e vice-chefe de departamento (2008). Membro da Comissão da Farmacopeia Brasileira (2008-2013): Comitê Técnico Temático de Plantas Medicinais (desde 2008), e Comitê Técnico Temático de Marcadores e Padrões de Fitoterápicos (2012-2013). Membro da Sociedade Brasileira de Farmacognosia (secretário: 2009-2011; e vice-presidente 2013-2015) e da Associação Brasileira de Ciências Farmacêuticas - ABCF (1o tesoureiro: 2012-2013; e, conselho fiscal 2013-2015). Atualmente é Professor Associado do Departamento de Ciências Farmacêuticas da UFPE (DEZ/2008) e vice-coordenador do Programa de Pós-Graduação em Inovação Terapêutica PPGIT/CCB/UFPE (2013-2015). Bolsista PQ2/CNPq (desde 2009) e PDE CAPES/DAAD (Uni-Tübingen, 2015), tem experiência nas áreas de Tecnologia Farmacêutica e Controle de Qualidade, com ênfase em desenvolvimento analítico e tecnológico de Fitoterápicos.

Luana Costa

Universidade Federal de Pernambuco (UFPE), Programa de Pós-Graduação em Ciências Farmacêuticas, Recife, PE, Brasil.

Magda Ferreira

Universidade Federal de Pernambuco (UFPE), Programa de Pós-Graduação em Ciências Farmacêuticas, Recife, PE, Brasil. Universidade Federal de Pernambuco (UFPE), Programa de Pós-Graduação em Inovação Terapêutica, Recife, PE, Brasil.

Tatiane Souza

Universidade Federal do Amazonas (UFAM), Faculdade de Ciências Farmacêuticas, Manaus, AM, Brasil.


The aim of this study was to evaluate the influence of the qualitative composition of excipients on formulation technology of hard gelatin capsules containing high amount of dry extract from Aesculus hippocastanum L. (ESAH). The rheological and technological characteristics of ESAH were determined and the influence of pharmaceutical excipients on the properties of mixtures was studied by a 22 factorial design. The dissolution profiles of the capsules containing the best mixtures were obtained using sodium lauryl sulfate aqueous solution 1% (w/v) as medium. The ESAH showed high cohesivity and therefore low flow. Moreover, the ESAH showed lower level of residual moisture and was stable under controlled atmosphere. When considering pre-formulation, the filler/binder materials (microcrystalline cellulose or lactose) and glidant (colloidal silicon dioxide) increased the technological properties of the mixtures in comparison to pure ESAH. In conclusion, the dissolution profiles showed that there was no significant difference between the formulations and the ESAH, which demonstrated totally release after 30 minutes.


  1. BALAKRISHNAN, A.; REGE, B.D.; AMIDON, G.L.; POLLI, J.E. Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity. Elsevier. Journal of Pharmaceutical Sciences. v. 93, p. 2064-2075, USA. 2004. ISSN 1520-6017. [PubMed]
  2. BAUER, K.H.; FRÖMMING, K.H.; FÜHRER, C. Pharmazeutische Technologie. 9. Aufl., Stuttgart, WVG. 2012. ISBN 978-3804725522.
  3. BOMBARDELLI, E.; MORAZZONI, P.; GRIFFINI, A. Aesculus hippocastanum L. Fitoterapia. v. 6, p. 483-511, 1996.
  4. CARR, R.L. Evaluating Flow Properties of Solids. Chemical Engineering. v.72, p. 163-168, 1965.
  5. COUTO, R.O.; CONCEICAO, E.C.; CHAUL, L.T.; OLIVEIRA, E.M.S; MARTINS, F.S.; BARA, M.T.F; REZENDE, K.R.; ALVES, S.F.; PAULA, J.R. Spray-dried rosemary extracts: Physicochemical and antioxidant properties. Food Chemistry. v. 131, p. 99–105, 2012. ISSN 0308-8146. [CrossRef]
  6. CRISON, J.R.; SHAH, V.P.; SKELLY, J.P.; AMIDON, G.L. Drug dissolution into micellar solutions: development of a convective diffusion model and comparison to the film equilibrium model with application to surfactant-facilitated dissolution of carbamazepine. Elsevier. Journal of Pharmaceutical Sciences. v. 85, p. 1005-1011, USA. 1996. ISSN 1520-6017.[PubMed]
  7. DAB. Deutsches Arzneibuch. Eingesteller Rokastaniensamentrockenextrakt. Deutscher Apotheker - Verlag Stuttgart, Govi - Verlag, Pharmazeutischer Verlag Escborn. 2004a.
  8. DAB. Deutsches Arzneibuch. Rokastaniensamen. Deutscher Apotheker - Verlag Stuttgart, Govi - Verlag, Pharmazeutischer Verlag Escborn. 2004b.
  9. DALLAVALLE, J.M. Micromeritics. The technology of fine particles. 2nd edition. New York: Pitman Publishing Corporation, 555 p. 1948.
  10. DE SOUZA, K.C.B.; PETROVICK, P.R.; BASSANI, V.L.; GONZÁLEZ ORTEGA, G. The adjuvants Aerosil 200 and Gelita - Sol - P Influence on the technological characteristics of spray-dried powders from Passiflora edulis var. flavicarpa. Taylor&Francis. Drug Development and Industrial Pharmacy. v. 26, p. 331-336, USA. 2000. ISSN 1520-5762. [CrossRef] [PubMed]
  11. DE SOUZA, T.P.; BASSANI, V.L.; GONZÁLEZ ORTEGA, G.; DALLA COSTA, T.C.T.; PETROVICK, P.R. Influence of adjuvants on the dissolution profile of tablets containing high dose of spray-dried extract of Maytenus ilicifolia. Wiley. Pharmazie. v. 56, p.730-733, USA. 2001. ISSN 0031-7144. [PubMed]
  12. DE SOUZA, T.P.; GÓMEZ-AMOZA, J.L.; MATINEZ-PACHECO, R.; PETROVICK, P.R. Development of granules from Phyllanthus niruri spray-dried extract. SciElo. Brazilian Journal of Pharmaceutical Science. v. 45, p. 669-675, São Paulo. 2009. ISSN 21759790. [CrossRef]
  13. DE SOUZA, T.P.; MATINEZ-PACHECO, R.; GÓMEZ-AMOZA, J.L.; PETROVICK, P.R. Eudragit E as excipient for production of granules and tablets from Phyllanthus niruri L. spray dried extract. Springer. AAPS PharmSciTech. v. 8: Article. 34, USA. 2007. [CrossRef] [PubMed]
  14. DIN 66145. DIN Deutsches Institut für Normung. Darstellung von Korn-(teilchen-) grössenverteilungen-RRSB-Netz. DIN Taschenbuch 133- Partikelmesstechnik: Normen. Berlin, Germany: Beuth Verlag; 1997:191Y193.
  15. FAHR, A. VOIGT, R. Voigt. Pharmazeutische Technologie – Für Studium und Beruf. 12. Aufl., Stuttgart: Deutscher Apotheker Verlag. 2015. ISBN 3769235118.
  16. FB 5. Farmacopeia Brasileira. 5ª ed., Brasília: ANVISA. 2010. ISBN 978- 3769261943. [Link]
  17. FDA. Center for Drug Evaluation and Research. Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. Food and Drug Administration: Rockville. 2007. [Link]
  18. HAUSNER, H.H. Friction conditions in a mass of metal powder. APMI. International Journal of Powder Metallurgy. v. 3, p.7-13, USA. 1967. ISSN 08887462. [CrossRef]
  19. HÜBNER. G.; WRAY, V.; NAHRSTEDT, A. Flavonol oligosaccharides from the seeds of Aesculus hippocastanum. Thieme. Planta Medica. v.65, n.7, p. 636-642, USA. 1999. ISSN 0032-0943. [CrossRef] [PubMed]
  20. HURTADO, F.K.; RAVANELLO, A.; TORRES, B.G.S.; SOUTO, G.D.; BECK, R.C.R; ROLIM, C.M.B. Development of a discriminating in vitro dissolution method for the poorly soluble drug rimonabant: Effect of formulation variables on dosage form release profiles. Dissolution Technologies. August, p. 13-18, USA. 2012. ISSN 2376-869X. [CrossRef]
  21. JAMZAD, S.; FASSIHI, R. Role of Surfactant and pH on Dissolution Properties of Fenofibrate and Glipizide - A Technical Note. Springer. AAPS PharmSciTech. v.7, n.2, Article 33, USA. 2006. [CrossRef] [PubMed]
  22. JONAT, S.; HASENZAHL, S.; GRAY, A.; SCHMIDT, P.C. Mechanism of glidants: Investigation of the effect of different colloidal silicon dioxide types on powder flow by atomic force and scanning electron microscopy. Elsevier. Journal of Pharmaceutical Sciences. v. 93, p. 2636-2644, USA. 2004. ISSN 0022-3549. [CrossRef] [PubMed]
  23. KIM, M.Y. Composition containing horse chestnut extract for anti-angiogenic and matrix metalloproteinase inhibitory activity. Angiolab Inc. WO 03/035092 A1, 2003. [Link]
  24. KWAN, K.H.; HIGUCHI, W.I.; MOLOKHIA, A.M.; HOFMANN, A.F. Dissolution kinetics of cholesterol in simulated bile. 1: Influence of bile acid type and concentration, bile acid-lecithin ratio and added electrolyte. Elsevier. Journal of Pharmaceutical Sciences. v. 66, n.8, p. 1094-1101, 1977. ISSN 0022-3549. [CrossRef] [PubMed]
  25. LINDEN, R.; ORTEGA, G. G.; PETROVICK, P. R.; BASSANI, V. L. Response surface analysis applied to the preparation of tablets containing a high concentration of vegetable spray-dried extract. Taylor & Francis. Drug Development and Industrial Pharmacy. v. 26, p. 441-446, USA. 2000. ISSN 1520-5762. [CrossRef]
  26. MORIMOTO, S.; NONAKA, G.I.; NISHIOKA, I. Tannins and related compounds. LIX. Aesculitannins, novel proanthocyanidins with doubly-bonded structures from Aesculus hippocastanum L. The Pharmaceutical Society of Japan. Chemical and Pharmaceutical Bulletin. v. 35, p. 4717-4729, USA. 1987. ISSN 1347-5223. [CrossRef]
  27. MYERS, R.H.; MONTGOMERY, D.C; ANDERSON-COOK, C.M. Response Surface Methodology: Process and Product Otimization Using Designed Experiments. 3rd ed. Wiley, New York. 2009. ISBN 978-0470174463.
  28. NERURKAR, M.M.; HO, N.F.H.; BURTON, P.S.; VIDMAR, T.J.; BORCHARDT, R.T. Mechanistic roles of neutral surfactants on concurrent polarized and passive membrane transport of a model peptide in Caco-2 cells. Elsevier. Journal of Pharmaceutical Sciences. v.86, p. 813-821, USA. 1997. ISSN 0022-3549. [CrossRef] [PubMed]
  29. PITTLER, M. H.; ERNST, E. Horse-chestnut seed extract for chronic venous insufficiency. A criteria-based systematic review. The Jama Network. Archives of Dermatology. v. 134, n. 11, p. 1356-1360, USA. 1998. ISSN 0003-987X. [CrossRef] [PubMed]
  30. PODCZECK, F. Particle-particle Adhesion in Pharmaceutical Powder Handling. Imperial College Press, London. 1999. ISBN 978-1860941122.
  31. QUSAJ, Y.; LENG, A.; ALSHIHABI, F.; KRASNIQI, B.; VANDAMME, T. Development strategies for herbal products reducing the influence of natural variance in dry mass on tableting properties and tablet characteristics. Pharmaceutics. v. 4, n. 4, p.501-516, 2012. ISSN [CrossRef] [PubMed]
  32. RITCHEL, W.A.; BAUER-BRANDL, A. Die Tablette: Handbuch der Entwicklung, Herstellung und Qualitätssicherung. 3. Aufl. ECV, Aulendorf. 2011. ISBN 978-3871934070
  33. SHAH, V.P.; KONECNY, J.J.; EVERETT, R.L.; MCCULLOUGH, B.; NOORIZADEH, A.C.; SKELLY, J.P. In vitro dissolution profile of water-insoluble drug dosage forms in the presence of surfactants. Springer. Pharmaceutical Research. v .6, p. 612-618, USA. 1989. ISSN 1573-904X. [CrossRef] [PubMed]
  34. SHAH, V.P.; NOORY, A.; NOORY, C.; MCCULLOUGH, B.; CLARKE, S.; EVERETT, R.; NAVIASKY, H.; SRINIVASAN, B.N.; FORTMAN, D.; SKELLY, J.P. In vitro dissolution of sparingly water-soluble drug dosage forms. Elsevier. International Jounal of Pharmaceutics. v. 125, p. 99-106, USA. 1995. ISSN 0378-5173 [CrossRef]
  35. SIRTORI, C.R. Aescin: pharmacology, pharmacokinetics and therapeutic profile. Elsevier. Pharmacology Research. v.44, p. 183-193, USA. 2001. ISSN 1043-6618. [CrossRef] [PubMed]
  36. SOARES, L.A.L.; ORTEGA, G.G.; BASSANI, V.L.; PETROVICK, P.R.; SCHIMIDT, P.C. Dry granulation and compression of spray-dried plant extracts. Springer. AAPS PharmSciTech. v. 6, Article 45, USA. 2005a. ISSN 1530-9932. [CrossRef] [PubMed]
  37. SOARES, L.A.L.; ORTEGA, G.G.; BASSANI, V.L.; PETROVICK, P.R.; SCHMIDT, P.C. Optimization of tables containing high dose of spray-dried plant extracts. Springer. AAPS PharmSciTech, v.6, Article 46, USA. 2005b. ISSN 1530-9932. [CrossRef] [PubMed]
  38. SOARES, L.A.L.; SCHMIDT, P.C.; ORTEGA. G.G.; PETROVICK. P.R. Efeito da força e da velocidade de compressão sobre as propriedades de comprimidos contendo alta concentração de extrato seco vegetal. Colegio de Farmacéuticos. Acta Farmaceutica Bonaerense. v. 22, p. 147-154, Buenos Aires. 2003. ISSN 0326-2383.
  39. SOUZA, C.R.F.; SCHIAVETTO, I.A.; THOMAZINI, F.C.F.; OLIVEIRA, W.P. Processing of Rosmarinus officinalis Linne extract on spray and spouted bed dryers. SciElo. Brazilian Journal of Chemical Engineering. v. 25, p. 59-69, São Paulo. 2008a. ISSN 1678-4383. [CrossRef]
  40. SOUZA, C.R.F.; DONIDA, M.W.; ROCHA, S.C.S.; OLIVEIRA, W.P. The role of colloidal silicon dioxide in the enhancement of the drying of herbal preparations in suspended state. Taylor & Francis. Chemical Engineering Communications. v. 196, p. 391-405, USA. 2008b. ISSN 1563-5201. [CrossRef]
  41. SPANIOL, B.; BICA, V.C.; RUPPENTHAL, L.R.; VOLPATO, M.R.; PETROVICK, P.R. Compressional behavior of a mixture of granules containing high load of Phyllanthus niruri spray-dried extract and granules of adjuvants: Comparison between eccentric and rotary tablet machines. Springer. AAPS PharmSciTech. v. 10, p. 1013-1023, 2009. ISSN 1530-9932. [CrossRef] [PubMed]
  42. SRIJAYANTA, S.; RAMAN, A.; GOODWIN, B.L. A comparative study of the constituents of Aesculus hippocastanum und Aesculus indica. Mary Ann Liebert. Journal of Medicinal Food. v. 2, p. 45-50, USA. 1999. ISSN 1557-7600. [CrossRef] [PubMed]
  43. STRICKER, H. Arzneiformen-Entwicklung: Feste Zubereitungen. 1. Aufl., Heidelberg: Springer. 2003. ISBN 978-3-642-62393-6.
  44. TONG, H.H.Y.; WONG, S.Y.S.; LAW, M.W.L.; CHU, K.K.W.; CHOW, A.H.L. Anti-hygroscopic effect of dextran in herbal formulations. Elsevier. International Journal of Pharmaceutics. v. 363, p. 99-105, USA. 2008. ISSN 0378-5173. [CrossRef] [PubMed]
  45. TURRO, N.J.; YEKTA, A. Luminescent probes for detergent solutions, a simple procedure for the determination of the mean aggregation number of micelles. ACS Publications. Journal of the American Chemical Society. v. 100, p. 5951-5952, USA. 1978. ISSN 1520-5126. [CrossRef]
  46. VIGNAU, E.; LOISEL, C.; DEVEAUX, M.F.; CANTONI, P. Number of particle for the determination of size distribution from microscopic images. Elsevier. Powder Technology. v. 107, p. 243-250, USA. 2000. [CrossRef]
  47. WELLS, J.I. Pharmaceutical pre-formulation: the physicochemical properties of drug substances. London: Ellis Horwood. 1988. ISBN 978-0470211144
  48. YATSU, F.K.; BORGHETTI, G.S.; MAGALHÃES, F.; FERRAZ, H.G.; SCHENKEL. E.P.; BASSANI, V.L. Ilex paraguariensis Pellets from a spray-sried extract: development, characterization, and stability. Springer. AAPS PharmSciTech. v. 17, n. 2, p. 358-67, 2016. ISSN 1530-9932. [CrossRef] [PubMed]
  49. YOSHIKAWA, M.; HARADA, E.; MURAKAMI, T.; MATSUDA, H.; WARIISHI, N.; YAMAHARA, J.; MURAKAMI, N.; KITAGAWA, I. Escins-Ia, Ib, IIa, IIb, IIIa, bioactive triterpene oligoglycosides from the seeds of Aesculus hippocastanum L.: their inhibitory effects on ethanol absorption and hypoglycemic activity on glucose tolerance test. The Pharmaceutical Society of Japan. Chemical and Pharmaceutical Bulletin. v. 42, p. 1357-1359, USA. 1994. ISSN: 1347-5223. [CrossRef]

Artigos mais lidos pelo mesmo(s) autor(es)