Enhancement of ketoconazole dissolution rate by the liquisolid technique

Molaei, Mir-Ali; Osouli-Bostanabad, Karim; Adibkia, Khosro; Shokri, Javad; Asnaashari, Solmaz; Javadzadeh, Yousef

doi:10.2478/acph-2018-0025

Abstract

The study was conducted to enhance the dissolution rate of ketoconazole (KCZ) (a poorly water-soluble drug) using the liquisolid technique. Microcrystalline cellulose, colloidal silica, PEG400 and polyvinyl pyrrolidone (PVP) were employed as a carrier, coating substance, nonvolatile solvent and additive in the KCZ liquisolid compact formulation, respectively. The drug-to-PEG400 and carrier-to-coating ratio variations, PVP concentration and aging effects on the in vitro release behavior were assessed. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) data revealed no alterations in the crystalline form of the drug and the KCZ-excipient interactions within the process. The load factor and the drug release rate were significantly enhanced compared to directly compressed tablets in the presence of the additive. Increasing the PEG400-to-drug ratio in liquid medications enhanced the dissolution rate remarkably. The dissolution profile and hardness of liquisolid compacts were not significantly altered by keeping the tablets at 40 °C and relative humidity of 75 % for 6 months. With the proposed modification of the liquisolid process, it is possible to obtain flowable, compactible liquisolid powders of high-dose poorly-water soluble drugs with an enhanced dissolution rate.

References

1. M. Wesoły, K. Cal, P. Ciosek and W. Wróblewski, Influence of dissolution-modifying excipients in various pharmaceutical formulations on electronic tongue results, Talanta162 (2017) 203–209; https://doi.org/10.1016/j.talanta.2016.10.01810.1016/j.talanta.2016.10.018
Search in Google Scholar Back to article
2. A. Nokhodchi, C. M. Hentzschel and C. S. Leopold, Drug release from liquisolid systems: speed it up, slow it down, Expert Opin. Drug Deliv.8 (2011) 191–205; https://doi.org/10.1517/17425247.2011.54880110.1517/17425247.2011.548801
Search in Google Scholar Back to article
3. L. Azharshekoufeh, J. Shokri, M. B. Jalali and Y. Javadzadeh, Liquigroud technique: a new concept for enhancing dissolution rate of glibenclamide by combination of liquisolid and co-grinding technologies, BioImpacts7 (2017) 5–12; https://doi.org/10.15171/bi.2017.0210.15171/bi.2017.02
Search in Google Scholar Back to article
4. A. B. Karmarkar, I. D. Gonjar and A. H. Hosmani, Liquisolid technology for dissolution rate enhancement or sustained release, Expert Opin. Drug Deliv.7 (2010) 1227–1234; https://doi.org/10.1517/17425247.2010.51117310.1517/17425247.2010.511173
Search in Google Scholar Back to article
5. I. Theochari, M. Goulielmaki, D. Danino, V. Papadimitriou, A. Pintzas and A. Xenakis, Drug nanocarriers for cancer chemotherapy based on microemulsions: the case of Vemurafenib analog PLX4720, Colloids Surf. B Biointerfaces154 (2017) 350–356; https://doi.org/10.1016/j.colsurfb.2017.03.03210.1016/j.colsurfb.2017.03.032
Search in Google Scholar Back to article
6. M. Colombo, S. Staufenbiel, E. Rühl and R. Bodmeier, In situ determination of the saturation solubility of nanocrystals of poorly soluble drugs for dermal application, Int. J. Pharm.521 (2017) 156–166; https://doi.org/10.1016/j.ijpharm.2017.02.03010.1016/j.ijpharm.2017.02.030
Search in Google Scholar Back to article
7. K. Sigfridsson, P. Skantze, U. Skantze, L. Svensson, L. Löfgren, P. Nordell, E. Michaëlsson, B. Smedsrød, B. Fuglesteg and K. Elvevold, Nanocrystal formulations of a poorly soluble drug. 2. Evaluation of nanocrystal liver uptake and distribution after intravenous administration to mice, Int. J. Pharm.524 (2017) 248–256; https://doi.org/10.1016/j.ijpharm.2017.03.06210.1016/j.ijpharm.2017.03.062
Search in Google Scholar Back to article
8. R. Ghanavati, A. Taheri and A. Homayouni, Anomalous dissolution behavior of celecoxib in PVP/Isomalt solid dispersions prepared using spray drier, Mater. Sci. Eng. C72 (2017) 501–511; https://doi.org/10.1016/j.msec.2016.11.04210.1016/j.msec.2016.11.042
Search in Google Scholar Back to article
9. K. I. Shingel, M. Selyanin, M. C. Filion and F. Polyak, Solid dispersions of drugs in hyaluronan matrix: The role of the biopolymer in modulating drug activity in vivo, J. Drug Deliv. Sci. Technol.39 (2017) 140–146; https://doi.org/10.1016/j.jddst.2017.03.01810.1016/j.jddst.2017.03.018
Search in Google Scholar Back to article
10. P. Veres, M. Kéri, I. Bányai, I. Lázár, I. Fábián, C. Domingo and J. Kalmár, Mechanism of drug release from silica-gelatin aerogel. Relationship between matrix structure and release kinetics, Colloids Surf. B Biointerfaces152 (2017) 229–237; https://doi.org/10.1016/j.colsurfb.2017.01.01910.1016/j.colsurfb.2017.01.019
Search in Google Scholar Back to article
11. M. Lu, H. Xing, T. Yang, J. Yu, Z. Yang, Y. Sun and P. Ding, Dissolution enhancement of tadalafil by liquisolid technique, Pharm. Dev. Technol.22 (2017) 77–89; https://doi.org/10.1080/10837450.2016.118956310.1080/10837450.2016.1189563
Search in Google Scholar Back to article
12. K. T. Savjani, A. K. Gajjar, J and K. Savjani, Drug solubility: Importance and enhancement techniques, ISRN Pharm.2012 (2012) 1–10; https://doi.org/10.5402/2012/19572710.5402/2012/195727
Search in Google Scholar Back to article
13. T. L. Rogers, K. A. Overhoff, P. Shah, P. Santiago, M. J. Yacaman, K. P. Johnston and R. O. Williams, Micronized powders of a poorly water soluble drug produced by a spray-freezing into liquid-emulsion process, Eur. J. Pharm. Biopharm.55 (2003) 161–172; https://doi.org/10.1016/S0939-6411(02)00193-510.1016/S0939-6411(02)00193-5
Search in Google Scholar Back to article
14. Y. Javadzadeh, B. Jafari-Navimipour and A. Nokhodchi, Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine), Int. J. Pharm.341 (2007) 26–34; https://doi.org/10.1016/j.ijpharm.2007.03.03410.1016/j.ijpharm.2007.03.034
Search in Google Scholar Back to article
15. Y. Javadzadeh, M. R. Siahi, S. Asnaashari and A. Nokhodchi, Liquisolid technique as a tool for the enhancement of poorly water-soluble drugs and evaluation of their physicochemical properties, Acta Pharm.57 (2007) 99–109; https://doi.org/10.2478/v10007-007-0008-610.2478/v10007-007-0008-6
Search in Google Scholar Back to article
16. Y. Javadzadeh, M. Siahi-Shadbad, M. Barzegar-Jalali and A. Nokhodchi, Enhancement of dissolution rate of piroxicam using liquisolid compacts, Il Farmaco60 (2005) 361–365; https://doi.org/10.1016/j.farmac.2004.09.00510.1016/j.farmac.2004.09.005
Search in Google Scholar Back to article
17. V. De Campos, C. Cerqueira-Coutinho, F. Capella, B. Soares, C. Holandino and C. Mansur, Development and in vitro assessment of nanoemulsion for delivery of ketoconazole against Candida albicans, J. Nanosci. Nanotechnol.17 (2017) 4623–4630; https://doi.org/10.1166/jnn.2017.1344510.1166/jnn.2017.13445
Search in Google Scholar Back to article
18. P. Deng, F. Teng, F. Zhou, Z. Song, N. Meng and R. Feng, Methoxy poly (ethylene glycol)-b-poly (δ-valerolactone) copolymeric micelles for improved skin delivery of ketoconazole, J. Biomater. Sci. Polym. Ed.28 (2017) 63–78; https://doi.org/10.1080/09205063.2016.124437110.1080/09205063.2016.1244371
Search in Google Scholar Back to article
19. G. A. Abdelbary, M. M. Amin and M. Y. Zakaria, Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies, Drug Deliv.24 (2017) 309–319; https://doi.org/10.1080/10717544.2016.124792810.1080/10717544.2016.1247928
Search in Google Scholar Back to article
20. A. M. Stewart, M. E. Grass, D. M. Mudie, M. M. Morgen, D. T. Friesen and D. T. Vodak, Development of a biorelevant, material-sparing membrane flux test for rapid screening of bioavailability-enhancing drug product formulations, Mol. Pharm.14 (2017) 2032–2046; https://doi.org/10.1021/acs.molpharmaceut.7b0012110.1021/acs.molpharmaceut.7b00121
Search in Google Scholar Back to article
21. J. Bassi da Silva, S. B. d. S. Ferreira, O. de Freitas and M. L. Bruschi, A critical review about methodologies for the analysis of mucoadhesive properties of drug delivery systems, Drug Dev. Ind. Pharm.43 (2017) 1053–1070; https://doi.org/10.1080/03639045.2017.129460010.1080/03639045.2017.1294600
Search in Google Scholar Back to article
22. A. Ruff, T. Fiolka and E. S. Kostewicz, Prediction of Ketoconazole absorption using an updated in vitro transfer model coupled to physiologically based pharmacokinetic modelling, Eur. J. Pharm. Sci.100 (2017) 42–55; https://doi.org/10.1016/j.ejps.2016.12.01710.1016/j.ejps.2016.12.017
Search in Google Scholar Back to article
23. Y. Tsume, K. Matsui, A. L. Searls, S. Takeuchi, G. E. Amidon, D. Sun and G. L. Amidon, The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS), Eur. J. Pharm. Sci.102 (2017) 126–139; https://doi.org/10.1016/j.ejps.2017.02.04210.1016/j.ejps.2017.02.042
Search in Google Scholar Back to article
24. T. Loftsson and E. Stefánsson, Cyclodextrins and topical drug delivery to the anterior and posterior segments of the eye, Int. J. Pharm.531 (2017) 413–423; https://doi.org/10.1016/j.ijpharm.2017.04.01010.1016/j.ijpharm.2017.04.010
Search in Google Scholar Back to article
25. G. Balata, M. Mahdi and R. A. Bakera, Improvement of solubility and dissolution properties of ketoconazole by solid dispersions and inclusion complexes, Indian J. Pharm. Sci.5 (2011) 517–526; https://doi.org/10.4103/0250-474X.9899510.4103/0250-474X.98995
Search in Google Scholar Back to article
26. K. Inaba, T. Wakuda and K. Uekama, Prostaglandins and their cyclodextrin complexes, J. Incl. Phenom. Macrocycl. Chem.2 (1984) 467–474; https://doi.org/10.1007/BF0066221310.1007/BF00662213
Search in Google Scholar Back to article
27. P. Kanaujia, G. Lau, W. K. Ng, E. Widjaja, M. Schreyer, A. Hanefeld, M. Fischbach, C. Saal, M. Maio and R. B. Tan, Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy, Drug Dev. Ind. Pharm.37 (2011) 1026–1035; https://doi.org/10.3109/03639045.2011.55809110.3109/03639045.2011.558091
Search in Google Scholar Back to article
28. A. Gryczke, S. Schminke, M. Maniruzzaman, J. Beck and D. Douroumis, Development and evaluation of orally disintegrating tablets (ODTs) containing Ibuprofen granules prepared by hot melt extrusion, Colloids Surf. B Biointerfaces.86 (2011) 275–284; https://doi.org/10.1016/j.colsurfb.2011.04.00710.1016/j.colsurfb.2011.04.007
Search in Google Scholar Back to article
29. M. Dhanaraju, K. S. Kumaran, T. Baskaran and M. S. R. Moorthy, Enhancement of bioavailability of griseofulvin by its complexation with β-cyclodextrin, Drug Dev. Ind. Pharm.24 (1998) 583–587; https://doi.org/10.3109/0363904980908566310.3109/03639049809085663
Search in Google Scholar Back to article
30. Y. Javadzadeh, M. R. Siahi, S. Asnaashari and A. Nokhodchi, An investigation of physicochemical properties of piroxicam liquisolid compacts, Pharm. Dev. Technol.12 (2007) 337–343; https://doi.org/10.1080/1083745070124757410.1080/10837450701247574
Search in Google Scholar Back to article

Enhancement of ketoconazole dissolution rate by the liquisolid technique

Abstract

Paradigm

My account