«Dissertation Zur Erlangung des Doktorgrades der Naturwissenschaften Der Fakultät für Mathematik, Informatik und Naturwissenschaften der ...»
In Fig. 24 drug release from the liquisolid compacts LS-N and the conventional tablets are shown. It is obvious that the release from the liquisolid compacts LS-N was much faster than that from the conventional tablets. This may be attributed to the above mentioned dissolved state of the drug in these liquisolid compacts. However, in comparison to the liquisolid compacts LS-1 (Fig. 20) containing Avicel® and Aerosil® as carrier and coating materials, respectively, it is interesting, that the release from LS-N compacts was slower than that from LS-1 compacts within the first 10 min, although both formulations contained a 0.9 % drug solution in PEG 300 as liquid portion. The percentage of griseofulvin released from LS-1 compacts reached 95 % already after 5 min, while with LS-N compacts only a release of 82 % was observed within this time period. This initially slower release rate from LS-N compacts may be explained by the slower disintegration of LS-N compacts (Table 11) compared to LS-1 compacts, which disintegrated instantaneously. With LS-N compacts disintegration was the rate-limiting step and thus, drug release may be accelerated by increasing the amount of disintegrant in the formula resulting in faster disintegration.
Fig. 24: Drug release profiles of the liquisolid compacts LS-N and the conventional tablets (means ± SD; n = 3) Drug release enhancement from hydrophilic aerogels and liquisolid compacts 89
5.4 Conclusion Griseofulvin release from silica aerogel tablets and from liquisolid compacts is faster than that from conventional tablets containing the crystalline drug. Moreover, with liquisolid compacts containing the drug suspended in PEG 300 the release rate increases with rising percentage of dissolved drug in the liquid portion. Highest drug release rates are observed with liquisolid compacts containing a drug solution as liquid portion. Therefore, if the desired drug dose is high and/or the drug solubility in the liquid vehicle is low, a high amount of liquid vehicle is needed which in turn requires high amounts of carrier and coating materials. This results in an increase in tablet weight usually leading to an unacceptably large tablet size. Replacement of the commonly used carrier and coating materials Avicel® and Aerosil®, respectively, by the highly adsorptive silicate Neusilin® allows a considerably higher liquid loading capacity ultimately resulting in lower tablet weights.
 Spireas, S.
Liquisolid systems and methods of preparing same.
U.S. Patent 6423339B1 (2002)  Spireas, S., Jarowski, C.I., Rohera, B.D.
Powdered solution technology: principles and mechanism.
Pharm. Res. 9: 1351-1358 (1992)  Javadzadeh, Y., Siahi-Shadbad, M.R., Barzegar-Jalali, M., Nokhodchi, A.
Enhancement of dissolution rate of piroxicam using liquisolid compacts.
Farmaco 60: 361-365 (2005)  Javadzadeh, Y., Siahi, M.R., Asnaashari, S., Nokhodchi, A.
An investigation of physicochemical properties of piroxicam liquisolid compacts.
Pharm. Dev. Technol. 12: 337-343 (2007)  Nokhodchi, A., Javadzadeh, 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. 8: 18-25 (2005)  Yadav, V.B., Yadav, A.V.
Improvement of solubility and dissolution of indomethacin by liquisolid and compaction granulation technique.
J. Pharm. Sci. & Res. 1: 44-51 (2009)
 Nokhodchi, A., Hentzschel, C.M., Leopold, C.S.
Drug release from liquisolid systems: speed it up, slow it down.
Expert Opin. Drug Del. 8: 191-205 (2011)  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 4: 17-24 (2010)  Khaled, K.A., Asiri, Y.A., El-Sayed, Y.M.
In vivo evaluation of hydrochlorothiazide liquisolid tablets in beagle dogs.
Int. J. Pharm. 222: 1-6 (2001)  Spireas, S., Sadu, S., Grover, R.
In vitro release evaluation of hydrocortisone liquisolid tablets.
J. Pharm. Sci. 87: 867-872 (1998)  Karmarkar, A.B., Gonjari, I.D., Hosmani, A.H.
Liquisolid technology for dissolution rate enhancement or sustained release.
Expert Opin. Drug Del. 7: 1227-1234 (2010)  Spireas, S., Bolton, S.
Sustained-release "liquisolid compacts".
Proc. Int. Symp. Control. Rel. Bioact. Mater. 25: 138-139 (1998)  Spireas, S., Sadu, S.
Enhancement of prednisolone dissolution properties using liquisolid compacts.
Int. J. Pharm. 166: 177-188 (1998)
 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. 1: 115-122 (2009)  Gubbi, S., Jarag, R.
Liquisolid technique for enhancement of dissolution properties of bromhexine hydrochloride.
Research J. Pharm. and Tech. 2: 382-386 (2009)  Javadzadeh, Y., Jafari-Navimipour, B., Nokhodchi, A.
Liquisolid technique for dissolution rate enhancement of a high dose waterinsoluble drug (carbamazepine).
Int. J. Pharm. 341: 26-34 (2007)  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. 69: 993-1003 (2008)  Yadav, V.B., Yadav, A.V.
Enhancement of solubility and dissolution rate of BCS class II pharmaceuticals by nonaqueous granulation technique.
Int. J. Pharm. Res. Dev. 1: 1-12 (2010)  Karmarkar, A.B., Gonjari, I.D., Hosmani, A.H., Dhabale, P.N., Bhise, S.B.
Dissolution rate enhancement of fenofibrate using liquisolid tablet technique.
Lat. Am. J. Pharm. 28: 219-225 (2009)
 Akinlade, B., Elkordy, A.A., Essa, E.A., Elhagar, S.
Liquisolid systems to improve the dissolution of furosemide.
Sci. Pharm. 78: 325-344 (2010)  Darwish, I.A.E., El-Kamel, A.H.
Dissolution enhancement of glibenclamide using liquisolid tablet technology.
Acta Pharm. 51: 173-181 (2001)  Khaled, K.A.
Formulation and evaluation of hydrochlorothiazide liquisolid tablets.
Saudi Pharm. J. 6: 39-46 (1998)  Liao, C.C., Jarowski, C.I.
Dissolution rates of corticoid solutions dispersed on silicas.
J. Pharm. Sci. 73: 401-403 (1984)  Hentzschel, C.M., Alnaief, M., Smirnova, I., Sakmann, A., Leopold, C.S.
Hydrophilic silica aerogels and liquisolid systems - two drug delivery systems to enhance dissolution rates of poorly soluble drugs.
Proc. Int. Symp. Controlled Release Biact. Mater., Portland (2010) # 538  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. 57: 99-109 (2007)  Spireas, S., Wang, T., Grover, R.
Effect of powder substrate on the dissolution properties of methyclothiazide liquisolid compacts.
Drug Dev. Ind. Pharm. 25: 163-168 (1999)
 Javadzadeh, Y., Shariati, H., Movahhed-Danesh, E., Nokhodchi, A.
Effect of some commercial grades of microcrystalline cellulose on flowability, compressibility, and dissolution profile of piroxicam liquisolid compacts.
Drug Dev. Ind. Pharm. 35: 243-251 (2009)  Sheth, A., Jarowski, C.I.
Use of powdered solutions to improve the dissolution rate of polythiazide tablets.
Drug Dev. Ind. Pharm. 16: 769-777 (1990)  Yadav, V.B., Yadav, A.V.
Liquisolid granulation technique for tablet manufacturing: an overview.
J. Pharmacy Res. 2: 670-674 (2009)  Hentzschel, C.M., Sakmann, A., Leopold, C.S.
Flowability of liquisolid powder blends.
Proc. AAPS Annual Meeting & Exposition, Atlanta (2008) # 6239  Hentzschel, C.M., Sakmann, A., Leopold, C.S.
Suitability of various tableting excipients as carriers for liquisolid systems.
Proc. 7th World Meeting Pharm. Biopharm. Pharm. Technol., Malta (2010) # 61  Nokhodchi, A., Javadzadeh, Y., Mosaalrezaei, L.
Liquisolid technique for sustaining the drug release from compacts.
J. Pharm. Pharmacol. 59: A19-A20 (2007)  Javadzadeh, Y., Musaalrezaei, L., Nokhodchi, A.
Liquisolid technique as a new approach to sustain propranolol hydrochloride release from tablet matrices.
Int. J. Pharm. 362: 102-108 (2008)
 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. Biostruct. 4: 651-661 (2009)  Gruetzmann, R., Wagner, K.G.
Quantification of the leaching of triethyl citrate/polysorbate 80 mixtures from Eudragit RS films by differential scanning calorimetry.
Eur. J. Pharm. Biopharm. 60: 159-162 (2005)  Azarmi, S., Farid, J., Nokhodchi, A., Bahari-Saravi, S.M., Valizadeh, H.
Thermal treating as a tool for sustained release of indomethacin from Eudragit RS and RL matrices.
Int. J. Pharm. 246: 171-177 (2002)  Azarmi, S., Farid, D., Azodi-Deylami, S., Ghaffari, F., Nokhodchi, A.
The influence of thermal treatment on the release behavior of diclofenac sodium from acrylic matrices.
Pharm. Dev. Technol. 10: 233-239 (2005)  Shoaib, M.H., Siddiqi, S.A.S., Yousuf, R.I., Zaheer, K., Hanif, M., Rehana, S., Jabeen, S.
Development and evaluation of hydrophilic colloid matrix of famotidine tablets.
AAPS PharmSciTech 11: 708-718 (2010)  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. 69: 342-347 (2008)
 Saharan, V.A., Kukkar, V., Kataria, M., Gera, M., Choudhury, P.K.
Dissolution enhancement of drugs. Part I: technologies and effect of carriers.
Int. J. Health Res. 2: 107-124 (2009)  Saharan, V.A., Kukkar, V., Kataria, M., Gera, M., Choudhury, P.K.
Dissolution enhancement of drugs. Part II: effect of carriers.
Int. J. Health Res. 2: 207-223 (2009)  Kubo, H., Osawa, T., Takashima, K., Mizobe, M.
Enhancement of oral bioavailability and pharmacological effect of 1-(3,4dimethoxyphenyl)-2,3-bis(methoxycarbonyl)-4-hydroxy-6,7,8trimethoxynaphthalene (TA-7552), a new hypocholesterolemic agent, by micronization in co-ground mixture with D-mannitol.
Biol. Pharmacol. Bull. 19: 741-747 (1996)  Lin, S.L., Menig, J., Lachman, L.
Interdependence of physiological surfactant and drug particle size on the dissolution behavior of water-insoluble drugs.
J. Pharm. Sci. 57: 2143-2148 (1968)  Aguiar, A.J., Zelmer, J.E., Kinkel, A.W.
Deaggregation behavior of a relatively insoluble substituted benzoic acid and its sodium salt.
J. Pharm. Sci. 56: 1243-1252 (1967)  Smirnova, I., Suttiruengwong, S., Seiler, M., Arlt, W.
Dissolution rate enhancement by adsorption of poorly soluble drugs on hydrophilic silica aerogels.
Pharm. Dev. Technol. 9: 443-452 (2004)
 Smirnova, I., Suttiruengwong, S., Arlt, W.
Feasibility study of hydrophilic and hydrophobic silica aerogels as drug delivery systems.
J. Non-Cryst. Solids 350: 54-60 (2004)  Sugimoto, M., Okagaki, T., Narisawa, S., Koida, Y., Nakajima, K.
Improvement of dissolution characteristics and bioavailability of poorly watersoluble drugs by novel cogrinding method using water-soluble polymer.
Int. J. Pharm. 160: 11-19 (1998)  Fujii, M., Okada, H., Shibata, Y., Teramachi, H., Kondoh, M., Watanabe, Y.
Preparation, characterization, and tableting of a solid dispersion of indomethacin with crospovidone.
Int. J. Pharm. 293: 145-153 (2005)  Barzegar-Jalali, M., Valizadeh, H., Shadbad, M.R.S., Adibkia, K., Mohammadi, G., Farahani, A., Arash, Z., Nokhodchi, A.
Cogrinding as an approach to enhance dissolution rate of a poorly watersoluble drug (gliclazide).
Powder Technol. 197: 150-158 (2010)  Bahl, D., Bogner, R.H.
Amorphization of indomethacin by co-grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism.
Pharm. Res. 23: 2317-2325 (2006)
 Loftsson, T., Brewster, M.E.
Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization.
J. Pharm. Sci. 85: 1017-1025 (1996)  Casella, R., Williams, D.A., Jambhekar, S.S.
Solid-state β-cyclodextrin complexes containing indomethacin, ammonia and water. II. Solubility studies.
Int. J. Pharm. 165: 15-22 (1998)  Ruan, L.P., Yu, B.Y., Fu, G.M., Zhu, D.N.
Improving the solubility of ampelopsin by solid dispersions and inclusion complexes.
J. Pharm. Biomed. Anal. 38: 457-464 (2005)  Albers, E., Mueller, B.W.
Cyclodextrin derivatives in pharmaceutics.
Crit. Rev. Ther. Drug Carr. Syst. 12: 311-337 (1995)  Jansook, P., Loftsson, T.
CDs as solubilizers: Effects of excipients and competing drugs.
Int. J. Pharm. 379: 32-40 (2009)  Pan, R.N., Chen, J.H., Chen, R.R.L.
Enhancement of dissolution and bioavailability of piroxicam in solid dispersion systems.
Drug Dev. Ind. Pharm. 26: 989-994 (2000)
 Valizadeh, H., Zakeri-Milani, P., Barzegar-Jalali, M., Mohammadi, G., DaneshBahreini, M.A., Adibkia, K., Nokhodchi, A.
Preparation and characterization of solid dispersions of piroxicam with hydrophilic carriers.
Drug Dev. Ind. Pharm. 33: 45-56 (2007)  Valizadeh, H., Nokhodchi, A., Qarakhani, N., Zakeri-Milani, P., Azarmi, S., Hassanzadeh, D., Loebenberg, R.
Physicochemical characterization of solid dispersions of indomethacin with PEG 6000, Myrj 52, lactose, sorbitol, dextrin and Eudragit® E100.
Drug Dev. Ind. Pharm. 30: 303-317 (2004)  Verheyen, S., Blaton, N., Kinget, R., Van den Mooter, G.
Mechanism of increased dissolution of diazepam and temazepam from polyethylene glycol 6000 solid dispersions.
Int. J. Pharm. 249: 45-58 (2002)  Craig, D.Q.M.