Enhancing of drug bioavailability using liquisolid system formulation
Authors:
Jan Gajdziok; Barbora Vraníková
Authors‘ workplace:
Ústav technologie lékÛ
; Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta
Published in:
Čes. slov. Farm., 2015; 64, 55-66
Category:
Review Articles
Overview
One of the modern technologies of how to ensure sufficient bioavailability of drugs with limited water solubility is represented by the preparation of liquisolid systems. The functional principle of these formulations is the sorption of a drug in a liquid phase to a porous carrier (aluminometasilicates, microcrystalline cellulose, etc.). After addition of further excipients, in particular a coating material (colloidal silica), a powder is formed with the properties suitable for conversion to conventional solid unit dosage forms for oral administration (tablets, capsules). The drug is subsequently administered to the GIT already in a dissolved state, and moreover, the high surface area of the excipients and their surface hydrophilization by the solvent used, facilitates its contact with and release to the dissolution medium and GI fluids. This technology, due to its ease of preparation, represents an interesting alternative to the currently used methods of bioavailability improvement. The article follows up, by describing the specific aspects influencing the preparation of liquid systems, on the already published papers about the bioavailability of drugs and the possibilities of its technological improvement.
Key words:
liquisolid systems • bioavailability • porous carrier • coating material • preformulation studies
Sources
1. Kawabata Y., Wada K., Nakatani M., Yamada S., Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm. 2011; 420, 1–10.
2. Okáčová L., Vetchý D., Franc A., Rabišková M., Kratochvíl B. Zvýšení biodostupnosti těžce rozpustných léčivých látek jejich modifikací. Chem. Listy 2010; 104, 21–26.
3. Balakrishnan A., Rege B. D., Amidon G. L., Polli E. Surfactant-mediated dissolution: Contributions of solubility enhancement and relatively low micelle diffusivity. J. Pharm. Sci. 2004; 93, 2064–2075.
4. Bajaj H., Bisht S., Yadav M., Singh V. Bioavaolability enhancement: a review. International Journal of Pharma and Bio Sciences 2011; 2, 202–216.
5. Sikarra D., Shukla V., Kharia A. A., Chatterjee D. P. Techniques for solubility enhancement of poorly soluble drugs: an overview. Journal of Medical Pharmaceutical and Allied Sciences 2012; 1, 1–22.
6. Li P., Yhao L. Solubilization of flurbiprofen in pH-surfactant solutions. J. Pharm. Sci. 2003; 92, 951–956.
7. Rangel-Yagui C. O., Pessoa Jr. A., Taveres L. C. Micellar solubilization of drugs. J. Pharm. Pharm. Sci. 2005; 8, 147–163.
8. Zhu J., Bierwagen G. P. The surface chemistry of water-reducible polymer solutions/dispersions – 1. Surface tension behavior. Prog. Org. Coat. 1995; 26, 87–100.
9. Kawakami K., Oda N., Miyoshi K., Funaki T., Ida Y. Solubilization behavior of a poorly soluble drug under combined use of surfactants and cosolvents. Eur. J. Pharm. Sci. 2006; 28, 7–14.
10. Vemula V. R., Lagishetty V., Lingala S. Solubility enhancement techniques. International Journal of Pharmaceutical Sciences Review and Research 2010; 5, 41–51.
11. Jangher A., Griffiths P. C., Paul A., King S. M., Heenan R. K., Schweins R. Polymeric micelle disruption by cosolvents and anionic surfactants. Colloid and Surface A 2011; 391, 88–94.
12. Patil A. E., Devtalu S. V., Bari M. M., Barthel S. D. A review on: novel solubility enhancement technique hydrotropy. Indo American Journal of Pharmaceutical Research 2013; 3, 4670–4679.
13. Kumar V. S., Raja C., Jayakumar C. A review on solubility enhancement using hydrotropic phenomena. International Journal of Pharmacy and Pharmaceutical Sciences 2014; 6, 1–7.
14. Terao K., Nakata D., Fukumi H., Schmid G., Arima H., Hirayama F., Uekama K. Enhancement of oral bioavailability of coenzyme Q10 by complexation with γγ-cyclodextrin in healthy adults. Nutr. Res. 2006; 26, 503–508.
15. Gowardhane A. P., Kadam N. V., Dutta S. Review on enhancement of solubilisation precess. Journal of Pharmacy and Phytotherapeutics 2013; 2, 28–38.
16. Kataria M. K., Bhandari A. Solubility and dissolution enhancement: technologies and research emerged. Journal of Biological and Scientific Opinion 2013; 1, 105–116.
17. Dvořáčková K. Principy uvolňování léčiv z perorálních matricových tablet obsahujících hypromelosu. Chem. Listy 2009; 103, 66–72.
18. Okáčová L., Vetchý D., Franc A, Rabišková M. Zvýšení biodostupnosti těžce rozpustných léčivých látek technologickými postupy usnadňujícími jejich rozpouštění. Chem. Listy 2011; 105, 34–40.
19. Sinha S., Ali M., Baboota S., Ahuja A., Kumar A., Ali J. Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech. 2010; 11, 518–527.
20. Baek H. H., Kim D. H., Kwon S. Y., Rho S. J., Kim D. W., Choi H. G., Kim Y. R., Yong C. S. Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose. Arch. Pharm. Res. 2012; 35, 683–689.
21. Zatloukal Z. Interaktivní práškové směsi. Čes. slov. Farm. 2004; 53, 165–171.
22. Allahham A., Stewart P. J. Enhancement of the dissolution of indomethacin in interactive mixtures using added fine lactose. Eur. J. Pharm. Biopharm. 2007; 67, 732–742.
23. Watano S., Imada Y., Hamada K., Wakamatsu Y., Tanabe Y., Dave R. N., Pfeffer R. Microgranulation of fine powders by a novel rotating fluidized bed granulation. Powder Technol. 2003; 131, 250–255.
24. Planinšek O., Kovačič B., Vrečer F. Carvediol dissolution improvement by preparation of solid dispersions with porous silica. Int. J. Pharm. 2011; 406, 41–48.
25. Krupa A., Jachowicz R., Kurek M., Figiel W., Kwiecień M. Preparation of solid self-emulsifying drug delivery systems using magnesium aluminometasilicates and fluid-bed coating proces. Powder Technol. 2014; 266, 329–339.
26. Yang H., Teng F., Wang P., Tian B., Lin X., Hu X., Zhang L., Zhang K., Zhang Y., Tang Y. Investigation of a nanosuspension stabilized by Soluplus® to improve bioavailability. Int. J. Pharm. 2014; 477, 88–95.
27. Shaikh J., Ankola D. D., Beniwal V., Singh D., Kumer M. N. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur. J Pharm. Sci. 2009; 37, 223–230.
28. Chen Y., Lu Y., Chen J., Lai J., Sun J., Hu F., Wu W. Enhanced bioavailability of the poorly water-soluble drug fenofibrate by using liposomes containing a bile salt. Int. J. Pharm. 2009; 376, 153–160.
29. Kulkarni S. A., Aloorkar N. H., Mane M. S. Liquisolid systems: A review. International Journal of Pharmaceutical Sciences and Nanotechnology 2010; 3, 795–802.
30. Kavitha K., Lova Raju K. N. S., Ganesh N. S., Ramesh B. Effect of dissolution rate by liquisolid compacts approach: An Overview. Der Pharmacia Lettre 2011; 3, 71–83.
31. Nokhodchi A., Hentzschel C. M., Leopold C. S. Drug release from liquisolid systems: speed it up, slow it down. Expert Opin. Drug Del. 2011; 8, 191–205.
32. Spireas S., Bolton S. M. Liquisolid systems and methods of preparing same. US 2002; 6, 339, 423.
33. Javadzadeh Y., Musaalrezaei L., Nokhodchi A. Liquisolid technique as a new approach to sustain propranolol hydrochloride release from tablet matrices. Int. J. Pharm. 2008; 362, 102–108.
34. Tang B., Cheng G., Gu J. C., Xu C. H. Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov. Today 2008; 13, 616–612.
35. Karmarkar A. B., Gonjari I. D., Hosmani A. H., Dhabale P. N., Bhise S. B. Liquisolid tablets: a novel approach for drug delivery. Int. J. Health. Res. 2009; 2, 45–50.
36. Nagabandi V. K., Ramarao T., Jayaveera K. N. Liquisolid compacts: A novel approach 30. to enhance bioavailability of poorly soluble drugs. International Journal of Pharmacy and Biological Sciences 2011; 1, 89–102.
37. El-Hammadi M., Awad N. Investigating the use of liquisolid compacts technique to minimize the influence of pH variations on loratadine release. AAPS PharmSciTech. 2012; 13, 53–58.
38. Spireas S., Bolton S. M. Liquisolid systems and methods of preparing same. US 1998; 5, 800, 834.
39. Javadzadeh Y., Siahi M. R., Asnaashari S., Nokhodchi A. Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and evaluation of their physicochemical properties. Acta Pharm. 2007; 57, 99–109.
40. Gavali S. M., Pacharane S. S., Sankpal S. V., Jadhav K. R., Kadam V. J. Liquisolid compact: A new technique for enhancement of drug dissolution. International Journal of Research in Pharmacy and Chemistry 2011; 1, 705–713.
41. Gubbi S., Jarag R. Formulation and characterization of atorvastatin calcium liquisolid compacts. Asian Journal of Pharmaceutical Sciences 2010; 5, 50–60.
42. Hentzschel C. M., Alnaief M., Smirnova I., Sakmann A., Leopold C. S. Enhancement of griseofulvin release from liquisolid compacts. Eur. J. Pharm. Biopharm. 2012; 80, 130–135.
43. Tayel S. A., Soliman I. I., Louis, D. Improvement of dissolution properties of carbamazepine through application of the liquisolid tablet technique. Eur. J. Pharm. Biopharm. 2008; 69, 342–347.
44. Zhao X., Zhou Y. Q., Potharaju S., Lou H., Sun H. M., Bruson E., Almoazen H., Johnson J. Development of a self micro-emulsifying tablet of cyclosporine A by the liquisolid compact technique. International Journal of Pharmaceutical Sciences and Research 2011; 2, 2299–2308.
45. Yada, A. V., Shete S. A., Dabke A. P. Formulation and evaluation of orodispersible liquisolid compacts of aceclofenac. Indian J. Pharm. Educ. 2010; 44, 227–235.
46. Gonjari I. D., Karmarkar A. B., Hosmani A. H. Evaluation of in vitro dissolution profile comparison methods of sustained release tramadol hydrochloride liquisolid compact formulations with marketed sustained release tablets. Dig. J. Nanomater. Bios. 2009; 4, 651–661.
47. Nokhodchi A., Aliakbar R., Desai S., Javadzadeh Y. Liquisolid compacts: The effect of cosolvent and HPMC in theophylline release. Colloid Surface B 2010; 79, 262–269.
48. Vraníková B., Gajdziok J. Liquisolid systems and aspects influencing their research and development. Acta Pharm. 2013; 63, 447–465.
49. El-Say K. M., Samy A. M., Fetouh M. I. Formulation and evaluation of rofecoxib liquisolid tablets. International Journal of Pharmaceutical Sciences Review and Research 2010; 3, 135–142.
50. Hentzschel C. M., Sakmann A., Leopold C. S. Suitability of various excipients as carrier and coating materials for liquisolid compacts. Drug. Dev. Ind. Pharm. 2011; 37, 1200–1207.
51. Tiong N., Elkordy A. A. Effects of liquisolid formulations on dissolution of naproxen. Eur. J. Pharm. Biopharm. 2009; 73, 373–384.
52. Spireas S. S., Jarowski C. I., Rohera B. D. Powdered solution technology: Principles and mechanism. Pharm. Res. 1992; 9, 1351–1358.
53. Karmarkar A. B., Gonjari I. D., Hosmani A. H. Liquisolid technology for dissolution rate enhancement or sustained release. Expert Opi. Drug. Deliv. 2010; 7, 1227–1234.
54. Khanfar M., Sheikh S. M., Hawari R. Formulation factors affecting the release of ezetimibe from different liquisolid compacts. Pharm. Dev. Technol. 2013; 18, 417–427.
55. Spireas S., Bolton S. M. Liquisolid systems and methods of preparing same, US 5,968,550, 1999.
56. Rajesh K., Rajalakshmi R., Umamaheswari J., Ashok Kumar C. K. Liquisolid technique a novel approach to enhance solubility and bioavailability. International Journal of Biopharmaceutics 2011; 2, 8–13.
57. Elkordy A. A., Essa E. A., Dhuppad S., Jammiqumpula P. Liquisolid technique to enhance and to sustain griseofulvin dissolution: effect pf choice of non-volatile liquid vehicles. Int. J. Phar. 2012; 434, 122–132.
58. Grover R., Spireas S., Lau-Cam C. Development of a simple spectrophotometric method for propylene glycol detection in tablets. J. Pharm. Biomed. Anal. 1998; 16, 931–938.
59. Suliman A. S., Anderson R. J., Elkordy A. A. Norfloxacin as a model hydrophobic drug with unique release from liquisolid formulations prepared with PEG200 and Synperonic PE/L-61 non-volatile liquid vehicles. Powder Technol. 2014; 257, 156–167.
60. Sirisha V. N. L., Sruthi B., Namrata M., Bhavani Harika I., Kirankumar P., Kiran Kumar Rao Y., Pravani K., Sindhura S., Camsi Krishna N., Uma Maheshwar Rao O. A Review on liquid solid compacts. International Journal of Pharmaceutical and Phytopharmacological Research 2012; 2, 116–121.
61. Adibkia K., Shokri J., Barzegar-Jalali M., Solduzian M., Javadzadeh Y. Effect of solvent type on retardation properties of diltiazem HCl form liquisolid tablets. Colloids Surf. B: Biointerfaces 2014; 113, 10–14.
62. Elkordy A. A., Tan X. N., Essa E. A. Spironolactone release from liquisolid formulations prepared with CapryolTM 90, Solutol® HS-15 and Kollicoat® SR 30 D as a non-volatile liquid vehicles. Eur. J. Pharm. Biopharm. 2013; 83, 203–223.
63. Thakur N., Khokra S. L., Sharma D., Thakur N. S., Purohit R., Arya V. A review on pharmaceutical applications of liquisolid technique. American Journal of PharmTech Research 2011; 1, 1–18.
64. NTP-CERHR Expert Panel report on the reproductive and developmental toxicity of propylene glycol. Reprod Toxicol 2004; 18, 533–579.
65. Propylene Glycol – Pharmaceutical. http://www.propylene-glycol.com/index.php/propylene-glycol-ups-ep-pharmaceutical-grade/pharmaceuticals. (17. 7. 2014).
66. Chella N., Shastri N., Tadikonda R. R. Use of the liquisolid compact technique for improvement of the dissolution rate of valsartan. Acta Pharm. Sinica B 2012; 2, 502–508.
67. Jabbar A. S. A., Hussein A. A. Formulation and evaluation of piroxicam liquisolid compacts. International Journal of Pharmacy and Pharmaceutical Sciences 2013; 5, 132–141.
68. Pavani E., Noman S., Syed I. A. Liquisolid technique based sustained release tablet of trimetazidine dihydrochloride. Drug Invention Today 2013; 5, 302–310.
69. Mahajan H. S., Dhamne M. R., Gattani S. G., Rasal A. D., Shaikh H. T. Enhanced disolution rate of glipizide by a liquisolid technoque. Int. J. Pharm. Sci. Nanotech. 2011; 3, 1205–1213.
70. Saeedi M., Akbari J., Morteza-Semnani K., Enayati-Fard R., Sar-Reshteh-dar S., Soleymani A. Enhancement of dissolution rate of indomethacin using liquisolid compacts. Iran. J. Pharm. Res. 2011; 10, 25–34.
71. Kutza C., Metz H., Kutza J. Toward a detailed characterization of oil adsorbates as “solid liquids”. Eur. J. Pharm. Biopharm. 2013; 84, 72–182.
72. Yadav V. B., Nighute A. B., Yadav A. V., Bhise S. B. Aceclofenac size enlargement by non aqueous granulation with improved solubility and dissolution. Arch. Pharm. Sci. Res. 2009; 1, 115–122.
73. Manogar P. G., Hari B. N. V., Devi D. R. Emerging liquisolid compact technology for solubility enhancement of BCSclass-II drug. J. Pharm. Sci. Res. 2011; 3, 1604–1611.
74. Akinlade B., Elkordy A. A., Essa E. A., Elhagar S. Liquisolid systems to improve the dissolution of furosemide. Sci. Pharm. 2010; 78, 325–344.
75. Kapure V. J., Pande V. V., Deshmukh K. P. Dissolution enhancement of rosuvastatin calcium by liquisolid compact technique. Journal of Pharmaceutics 2013; 2013, 1–9.
76. Lakshmi P. K., Srinivas C., Kalpana B. Preparation and comparative evaluation of liquisolid compacts and solid dispersions of valsartan. Stamford Journal of Pharmaceutical Sciences 2012; 4, 48– 57.
77. Ceolus. http://www.ceolus.com/en/ceolus_func.html. (9. 8. 2014).
78. van Eerdenbrugh B., Froyen, L., van Humbeeck J., Martens J., Augustijns P., van Den Mooter G. Alternative matrix formers for nanosuspension solidification: Dissolution performance and X-ray microanalysis as an evaluation tool for powder dispersion. Eur. J. Pharm. Sci. 2008; 35, 344–353.
79. Schlack H., Bauer-Brandl A., Schubert R., Becker D. Properties of Fujicalin®, a new modified anhydrous dibasic calcium phosphate for direct compression: comparison with dicalcium phosphate dihydrate. Drug. Dev. Ind. Pharm. 2001; 27, 789–801.
80. Fuji Chemical Industry Co., LTD. Fujicalin – product info. http://www.fujicalin.com/product/index.php. (5. 1. 2015).
81. Kang M. J., Jung S. Y., Song W. H., Park J. S., Choi S. U., Oh K. T., Choi H. K., Choi Y. W., Lee J., Lee B. J., Chi S. C. Immediate release of ibuprofen from Fujicalin®-based fast-dissolving self-emulsifying tablets. Dug. Dev. Ind. Pharm. 2011; 37, 1298–1305.
82. Prajapati S. T., Bulchandani H. H., Patel D. M., Dumaniya S. K., Patel C. N. Formulation and evaluation of liquisolid compacts for olmesartan medoxomil. J. Drug. Deliv. 2013; 2013, 1–9.
83. Luštická I., Vyskočilová-Leirmannová E., Červený L. Funkcionalizace mezoporézních silikátových materiálů. Chem. Listy 2013; 107, 114–120.
84. Chen B., Wang Z., Quan G., Peng X., Pan X., Wang R., Xu Y., Li G., Wu C. In vitro and in vivo evaluation of ordered mesoporous silica as a nocel adsorbent in liquisolid formulation. Int. J. Nanomed. 2012; 7, 199–209.
85. Zhu W., Wan L., Zhang C., Gao Y., Zheng X., Jiang T., Wang S. Exploitation of 3D face-centered cubic mesoporous silica as a carrier for a poorly water soluble drug: influence of pore size on release rate. Mater. Sci. Eng. C. Mater. Biol. Appl. 2014; 34, 78–85.
86. Vialpando M., Backhuijs F., Martens J. A., van den Mooter G. Risk assessment of premature drug release during wet granulation of ordered mesoporous silica loaded with poorly soluble compounds itraconazole, fenofibrate, naproxen, and ibuprofen. Eur. J. Pharm. Biopharm. 2012; 81, 190–198.
87. Wu Z., Jiang Y., Kim T., Lee K. Effects of surface coating on the controlled release of vitamin B1 from mesoporous silica tablets. J. Control. Release 2007; 119, 215–221.
88. Mellaerts R., Mols R., Jammaer J. A. G., Aerts C. A., Annaert P., van Humbeeck J., van den Mooter G., Augustijns P., Martens J. A. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica. Eur. J. Pharm. Biopharm. 2008; 69, 223–230.
89. van Speybroeck M., Mellaerts R., Mols R., Thi T. D., Martens J. A., van Humbeeck J., Annaert P., van den Mooter G., Augistijns P. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. Eur J Pharm Sci. 2010; 41, 623–630.
90. Mesoporous silica. http://news.easybranches.com/ wp–content/ uploads/2014/07/Mesoporous_silica_SEM-1-580x352.jpg (10. 4. 2015).
91. Chen B., Quan G., Wang Z., Chen J., Wu L., Xu Y., Li G., Wu C. Hollow mesoporous silicas as a drug solution delivery system for insoluble drugs. Powder Technol. 2013; 240, 48–53.
92. Fuji Chemical Industry Co., LTD. Neusilin – product info. http://www.neusilin.com/product/index.php. (6. 1. 2015).
93. Taniguchi H. Tabacco filter containing magnesium aluminometasilicate. EP 2,540,174 A1; 2013.
94. Krupa A., Majda D., Jachowicz R., Mozgawa W. Solid-state interaction of ibuprofen and Neusilin US2. Thermochim. Acta. 2010; 509, 12–17.
95. Sander C., Holm P. Porous magnesium aluminometasilicate tablets as carrier of a cyclosporine self-emulsifying formulation. AAPS PharmSciTech. 2009; 10, 1388–1395.
96. Hentzschel C. M., Alnaief M., Smirnova I., Sakmann A., Leopold C. S. Tableting properties of silica aerogels and other silicates. Drug. Dev. Ind. Pharm. 2012; 38,462–467.
97. Aerosil® fumed silica. https://www.aerosil.com/product/aerosil/en/ products/pages/default.aspx. (12. 8. 2014).
98. Fahmy R. H., Kassem M. A. Enhancement of famotidine dissolution rate through liquisolid tablets formulation: In vitro and in vivo evaluation. Eur. J. Pharm. Biopharm. 2008; 69, 993–1003.
99. Sharma S., Sher P., Badve S., Pawar A. P. Adsorption of Meloxicam on Porous Calcium Silicate: Characterization and Tablet Formulation. AAPS PharmSciTech. 2005; 6, 618–625.
100. El-Houssieny B. M., Wahman L. F., Arafa N. M. S. Bioavailability and biological activity of liquisolid compact formula of repaglinide and its effect on glucose tolerance in rabbits. Biosci. Trends. 2010; 4, 17–24.
101. Sheth A., Jarowski C. I. Use of powdered solutions to improve the dissolution rate of polythiazide tablets. Drug. Dev. Ind. Pharm. 1990; 16, 769–777.
102. Český lékopis 2009. 1. vydání. Praha: Grada Publishing 2009.
103. Syed I. A., Pavani E. The liquisolid technique: based drug delivery system. International Journal of Pharmaceutical Sciences and Drug Research 2012; 4, 88–96.
104. Kaur M., Bala R., Arora S. Formulation and evaluation of liquisolid compacts of amlodipine besylate. Intermational Research Journal of Pharma 2013; 4, 156–160.
105. Javadzadeh Y., Siahi-Shadbad M. R., Barzegar-Jalali M., Nokhodchi A. Enhancement of dissolution rate of piroxicam using liquisolid compacts. Farmaco 2005; 60, 361–365.
106. Nokhodchi A., Javadyadeh Y., Siahi-Shadbad M. R., Barzegar-Jalali M. The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts. J. Pharm. Pharm. Sci. 2005; 8, 18–25.
107. Khaled A., Asiri Y. A., El-Sayed Y. M. In vivo evaluation of hydrochlorothiazide liquisolid tablets in beagle dogs. Int. J Pharm. 2001; 222, 1–6.
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