Preparation and in vitro evaluation of Allopurinol-Gelucire 50/13 solid dispersions
Keywords:
Allopurinol, gelucire 50/13, closed melting-method, co-grinding, dissolution study, powder X-ray diffraction analysisAbstract
The rate-limiting step to absorption of drugs from the gastrointestinal tract is often dissolution from the dosage form. Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with leukaemia, radiotherapy, anti-neoplastic agents. One of the major problems with allopurinol is that, it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation method, kneading method, co-precipitation method, co-grinding method and closed melting method to increase its water solubility. In the present study amphiphilic carrier like gelucire 50/13 was used in the ratio of 1:1, 1:2 and 1:4. Prepared solid dispersions were characterized in the liquid state by phase solubility studies and in the solid state by Differential Scanning calorimetric analysis, Powder X-ray diffractometry and Fourier Transform Infrared spectroscopy. The aqueous solubility of allopurinol was preferential by the presence polymer with increasing concentration. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the current study showed that gelucire 50/13 has a significant solubilizing effect on allopurinol.
References
Merisko-Liversidge E, Liversidge GG, Cooper ER.
Nanosizing: a formulation approach for poorlywater-soluble compounds. Eur J Pharm Sci 2003;
: 113.
Serajuddin ATM. Salt formation to improve drug
solubility. Adv Drug Del Reviews 2007; 59: 603.
Vasconcelos T, Sarmento B, Costa P. Solid
dispersions as strategy to improve oral
bioavailability of poor water soluble drugs. Drug
Discovery Today 2007; 12: 1068-1075.
Ambike AA, Mahadik KR, Paradkar A. Stability
study of amorphous valdecoxib. Int J Pharm 2004;
: 151-162.
Paradkar A, Ambike AA, Jadhav BK.
Characterization of curcumin-PVP solid dispersion
obtained by spray drying. Int J Pharm 2004; 271:
-286.
Doshi DH, Ravis WR, Betageri GV.
Carbamazepine and polyethylene glycol solid
dispersion preparation, in vitro dissolution, and
characterization. Drug Dev Ind Pharm 1967; 23:
-1176.
Abdul-Fattah AM, Bhargava HN. Preparation and
in vitro evaluation of solid dispersions of
halfantrine. Int J Pharm 2002; 235: 17-33.
Fini A, Rodriguez C, Cavallari C. Ultrasoundcompacted and spray-congealed
indomethacin/polyethelyeneglycol systems. Int J
Pharm 2002; 247: 11-22.
Sethia S, Squillante E. Solid dispersion of
carbamazepine in PVP K30 by conventional
solvent evaporation and supercritical methods. Int
J Pharm 2004; 272: 1-10.
Pozzi F, Longo A, Lazzarini C. Formulations of
Ubidecarenone with improved bioavailability. Eur
J Pharm Biopharm 1991; 37: 243-246.
Passerini N, Perissutti B, Moneghini M.
Characterization of cabamazepine-Gelucire 50/13
microparticles prepared by a spray congealing
process using ultrasounds. J Pharm Sci 2002; 91:
-707.
Ahuja N, Singh A, Singh B. Rofecoxib: an update
on physicochemical, pharmaceutical,
pharmacodynamic and pharmacokinetic aspects. J
Pharm Pharmacol 2003; 55: 859-894.
Modi A, Tayade P. Enhancement of Dissolution
Profile by Solid Dispersion (Kneading) Technique.
AAPS PharmSciTech 2006; 7(3): 68.
Hasegawa S, Hamaura T, Furuyama N. Effects of
water content in physical mixture and heating
temperature on crystallinity of tropiglitazone- PVP
K30 solid dispersions prepared by closed melting
method. Int J Pharm 2005; 302: 103-112.
Ali N, Roya T, Hadi V. An Investigation on the
Solid Dispersions of Chlordiazepoxide. Int J
Biomed Sci 2007; 3(3): 211-217.
Dixit RP, Nagarsenkar MS. In vitro and In vivo
advantage of Celecoxib surface solid dispersion
and dosage form development. Indian J Pharm Sci
; 69(3): 370-377.
George Z, Bikiaris D, Karavas E. Effect of
Physical State and Particle Size Distribution on
Dissolution Enhancement of Nimodipine/PEG
Solid Dispersions Prepared by Melt Mixing and
Solvent Evaporation. AAPS PharmSciTech 2006;
(4): E623-E631.
Craig DQM. The use of glycerides as controlled
release matrices. In: Karsa DR, Stephenson RA
(Eds.), Excipients and delivery systems for
pharmaceutical formulations. Royal Society of
Chemistry London; 1995. p. 148-173.
Higuchi T, Connors KA. Phase solubility
techniques. 4th edi, Adv Anal Chem Instr 1965. p.
-212.
Ahuja N, Katare O, Singh B. Studies on
dissolution enhancement and mathematical
modeling of drug release of a poorly water-soluble
drug using water-soluble carriers. Eur J of Pharm
and Biopharm 2007; 65: 26–38.
Londhe VY, Nagarsenkar MS. Solid dispersion of
hydroxypropyl β- cyclodextrin and carbamazepine:
Study of complexation and in vitro dissolution
profile. Indian drugs 1999; 36(1): 15-20.
Mahaparale PR, Gudsoorkar VR, Gajeli GB.
Studies on Solid Dispersions of Meloxicam. Indian
J Pharm Edu Res (Oct – Dec) 2006; 40(4): 241-
Vippagunta SR, Maul KA, Tallavajhala S. Solidstate characterization of nifedipine solid
dispersions. Int J Pharm 2002; 236: 111–123.
