Effect of binary and ternary solid dispersions prepared by fusion method on the dissolution of poorly water soluble diacerein

Randa Mohamed Zaki, Adel Ahmed Ali, Shahira Fawzi El Menshawi, Ahmed Abdel Bary

Abstract


The poor solubility of drug substances in water and their low dissolution rate in aqueous G.I.T fluid often leads to insufficient bioavailability. The present investigation is an attempt to improve the solubility and dissolution rate of diacerein (a poorly soluble drug) by solid dispersion technique. Binary solid dispersions were made using PEG-4000 or PEG-6000 as carriers with varying drug: carrier ratios 1:1, 1:3 and 1:5. Also ternary solid dispersions were made using PEG-4000 and Pluronic F-68 at ratios 1:5:1, 1:5:2 and 1:5:3. Nine formulae were prepared and evaluated for saturated solubility, In-vitro drug release. Solid state characterization including DSC, FTIR, XRD and SEM is also carried out. All formulae showed marked significant improvement in the solubility and dissolution rate of the drug. The interaction studies showed no interaction between the drug and any of the used carriers. Formula SD9 (1:5:3; drug: PEG-4000: Pluronic F-68) showed the best dissolution profile with about 44.73% of the drug being released in the first 5 minutes and more than 79 % of the drug being released in the first 15 minutes. Also this formula showed the highest dissolution rate of 6.66 %/min. It was concluded that combination of PEG-4000 and Pluronic F-68 can be well utilized to improve the solubility of poorly soluble drugs.


Keywords


Diacerein, Solid dispersion, Polyethylene glycol, Physicochemical characterization; In-vitro dissolution.

Full Text:

PDF

References


- Jachowicz R, Nürnberg E, Pieszczek B, Kluczykowska B. Solid dispersion of ketoprofen in pellets. Int J Pharm. 2000; 206: 13–21.

- Dressman J, Leuner C. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000; 50: 47-60.

- Khoo S, Christopher JH, Charman WN. The formulation of Halofantrine as either non-solubilizing PEG-6000 or solubilizing lipid based solid dispersions: physical stability and absolute bioavailability assessment. Int J Pharm. 2000; 205(1-2): 65–78.

- Rajarajan S, Baby B, Ramesh K, Singh D. Preparation and evaluation of ternary mixing itraconazole solid dispersions by spray drying method. J Pharm Sci Res. 2009; 11(1): 22-25.

- Oneil M, Heckelman PE, Koch CB. In: The Merck Index. An Encyclopedia of Chemicals: Drugs and Biologicals, 14th ed., Merck, Whitehouse Station, NJ, USA, 2006; p. 503.

- Toegel S, Huang W, Piana C, Unger FM, Wirth M, Goldring MB, Gabor F. Selection of reliable reference genes for q PCR studies on chondroprotective action. BMC Mol Biol. 2007; 8:13.

- Tamura T, Shirai T, Kosaka N, Ohmori K, Takafumi N. Pharmacological studies of diacerein in animal models of inflammation arthritis and bone resorption. Eur J Pharmacol. 2002; 448: 81-87.

- Tamura T, Ohmori K. Rhehin. An active metabolite of diacerein, suppresses the interleukin-1α-inducedproteoglycan degradation in cultured rabbit articular chondrocytes. Jpn J Pharmacol. 2001; 85: 101-104.

- Diacerein Product Description. Xian Guanyu Bio- Tech Co. Ltd. (accessed on August 10, 2009). Available at http://www.bikudo.com/product_search/details/44285/diacerein.html

- Diacerein Capsules. Ostomod. (accessed on August 10, 2009). Available at http://www.cipladoc.com/therapeutic/pdf_cipla/ostomod.pdf

- Higuchi T, Connors KA. Phase-solubility techniques. Adv Anal Chem Instrum. 1965. 4; 117-210.

- Mukne AP, Nagarsenker MS. Triamterene β-cyclodextrin systems: preparation, characterization and in-vivo evaluation. AAPS PharmSciTech. 2004; 5: 19-24.

- Costa P, Sousa L. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001; 13(2): 123–133.

- Loftsson T, Masson M, Sigurjonsdottir JF. Methods to enhance the complexation efficiency of cyclodextrin. STP Pharma Sci. 1999; 9: 237–242.

- Zajc N, Obreza A, Bele M, Srcic S. Physical properties and dissolution behaviour of nifedipine/mannitol solid dispersions prepared by hot melt method. Int J Pharm. 2005; 291: 51–58

- Punitha S, Vedha Hari BN, Karthikeyan D. Enhancement of celecoxib solubility by solid disperson using mannitol. Int J Pharm Pharm Sci. 2010; 2(4): 109-111.

- Moore JW, Flanner H. Mathematical comparison of dissolution profiles. Pharm Technol. 1996; 20: 64–74.

- Ahuja N, Katare OP, Singh B. Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water soluble carriers. Eur J Pharm Biopharm. 2007; 65 (1): 26–38.

- O’Hara T, Dunne A, Butler J, Devane J. A review of methods used to compare dissolution profile data. Pharm Sci Technol To. 1998; 1(5): 214–223.

- Moneghinia M, Bellicha B, Baxab P, Princivalle F. Microwave generated solid dispersions containing ibuprofen. Int. J. Pharm. 2008; 361: 125-130.

- Higuchi T, Connors K. Phase solubility techniques. Adv Anal Chem Instrum. 1965; 4: 117–122.

- Mura P, Manderioli A, Bramanti G, Ceccarelli L. Properties of solid dispersions of naproxen in various polyethylene glycols. Drug Dev Ind Pharm. 1996; 22(9-10): 909–916.

- Serajudin ATM, Sheen PC, Augustine M A. Improved dissolution of poorly water soluble drug from solid dispersions in poly ethylene :polysorbste 80 mixtures. J Pharm Sci 1990; 79: 463–464.

- Serajuddin ATM, Sheen PC, Mufson D, Bernstein DF, Augustine MA. Effect of vehicle amphiphilicity on the dissolution and bioavailability of a poorly water-soluble drug from solid dispersions. J Pharm Sci. 1988; 77: 414–417.

- Biswal S, Sahoo J, Murthy PN, Giradkar RP. Enhancement of dissolution rate of gliclazide using solid dispersions with polyethylene glycol 6000. AAPS PharmSciTech. 2008; 9(2): 563–570

- Cirri M, Mura P, Rabasco AM, Gines JM, Moyano JR. Characterization of ibuproxam binary and ternary dispersions with hydrophilic carriers. Drug Dev Ind Pharm. 2004; 30(1): 65–74.

- Zerrouk N, Chemtob C, Arnaud P, Toscani S. In-vitro and in-vivo evaluation of carbamazepine–PEG 6000 solid dispersions. Int J Pharm. 2001; 225(1–2): 49–62.

- Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000; 50: 47-60.

- Kang BK, Lee JS , Chon SK, Jeong SY, Yuk SH. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm. 2004; 274: 65-73.

- Karavas E, Ktistis G, Xenakis A, Georgarakis E. Effect of hydrogen bonding interactions on the release mechanism of felodipine from nanodispersions with polyvinylpyrrolidone. Eur J Pharm Biopharm. 2006; 63: 103-114.

- Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006; 29: 278-287.

- Vasconcelos T, Costa P. Development of a rapid dissolving ibuprofen solid dispersion. 2007; In: PSWC – Pharmaceutical Sciences World Conference, DD-W-103

- Ghaderi R, Artursson P, Carifors J. Preparation of biodegradable microparticles using solution enhanced dispersion by supercritical fluids (SEDS). Pharm Res. 1999;16: 676-681.

- Pokharkar VB, Mandpe LP, Padamwar MN, Ambike AA, Mahadik KR. Development, characterization and stabilization of amorphous form of a low Tg drug. Powder Technol. 2006; 167: 20-25.

- Lioyd GR, Craig DQ, Smith A. A calorimetric investigation into the interaction between paracetamol and polyethylene glycol 4000 in physical mixes and solid dispersions. Eur J Pharm Biopharm.1999; 48: 59-65.

- Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res. 1997; 14: 1691-1698

- Dhirendra K, Lewis S, Udupa N, Atin K. Solid dispersions: A review. Pak J Pharm Sci. 2009; 22: 234-246.

- Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000; 50: 47-60.

- Mooter GV, Augustijns P, Blaton N and Kinget R. Physicochemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K-30. 1998. Int J Pharm; 164: 67-80.

- El-Maghraby GM, Alomrani AH. Synergistic enhancement of itraconazole dissolution by ternary system formation with Pluronic F-68 and hydroxypropyl-methylcellulose. 2009. Sci Pharm; 77: 401- 417.

- Wulff M, Aldén M. Solid state studies of drug cyclodextrin inclusion complexes in PEG 6000 prepared by a new method. Eur J Pharm Sci. 1999; 8: 269-281.

- Valleri M, Mura P, Maestrelli F, Cirri M, Ballerini R. Development and evaluation of glyburide fast dissolving tablets using solid dispersion technique. Drug Dev Ind Pharm. 2004; 30: 525-534.

- Ruan LP, Yu BY, Fu GM, Zhu DN. Improving the solubility of ampelopsin by solid dispersions and inclusion complexes. J Pharm Biomed Anal. 2005; 38: 457-464.

- Pignatello R, Ferro M, Puglisi G. Preparation of solid dispersions of non steroidal anti-inflammatory drugs with acrylic polymers and studies on mechanisms of drug polymer interactions. AAPS PharmSciTech. 2002; 3: E10.

- Soliman MS, Khan MA. Preparation and in-vitro characterization of a semi solid dispersion of flurbiprofen with Gelucire 44/14 and Labrasol. Pharmazie. 2005; 60: 288-293.

- Silverstein RM, Bassler GC, Morrill TC. Spectroscopic Identification of organic compounds. 5th ed., John Wiley and Sons Inc., NY, USA, 1991.


Refbacks

  • There are currently no refbacks.




Copyright (c)

               AR Journals

18K, Street 1st, Gaytri Vihar, Pinto Park, Gwalior, M.P. India

Copyright@arjournals.org (Design) 2009-2021

 

Follow @arjournals on Twitter