Development of oral Sustained release dosage form for low melting chiral compound Dexibuprofen and it’s in virto-in vivo evaluation
Keywords:
Dexibuprofen, Sustained release formulation, Xanthan Gum, Release Kinetic studies, Pharmacokinetic parametersAbstract
Newly developed single-unit of oral sustained release dosage form for low melting chiral compound, S (+)-ibuprofen have been prepared by the wet granulation method. The hydrophilic matrix was prepared with xanthan gum with additives Avicel PH101. In vitro drug release was carried out; these studies indicated that the drug release can be modulated by varying the concentration of the polymer and fillers. The data was evaluated according to zero-order, first-order, Higuchi and Peppas equations. A open, randomized, two-treatment, two period, single dose crossover, bioavailability study in 12 fasting, healthy, male, volunteers was conducted. After dosing, serial blood samples were collected for the period of 24.0 h. Various pharmacokinetic parameters including AUC0–t, AUC0–∞, Cmax, Tmax, T1/2, and elimination rate constant (Kel) were determined from plasma concentration of both formulations of test (Dexibuprofen 300 mg tablets) and reference (Dexibuprofen 300 mg tablets). The extent of absorption of drug from the sustained release tablets was significantly higher than that for the marketed dexibuprofen tablet because of lower elimination and longer half-life.
References
Hutt AJ, Caldwell F. The metabolic chiral
inversion of 2-acrylpropionic acids- a
novel route with pharmacological
consequences. J. Pharm. Pharmacol.
;35:693–704.
Lee EJD, Williams K, Day R, Graham G,
Champion D. Stereoselective disposition
of ibuprofen enantiomers in man, B. J.
Clin. Pharmacol. 1985;19:669–674.
Cheng H, Rogers JD, Demetriades JL, Ho
lland SD, Depuy E. Pharmac kinetics and
bioinversion of ibuprofen enantiomers in
humans. Pharm. Res. 1994;11:824–830.
Hogan JE. Hydroxypropylmethylcellulose
sustained release technology. Dr. Deve.
Ind. Pharm. 1989;15:975–999.
Huber HE, Christenson GL. Utilization of
hydrophilic gums for the control of drug
substance release from tablet
formulations. II Influence of tablet
hardness and density on dissolution
behavior, J. Pharm. Sci. 1968;57:164–
Menon S, Kadam N, Patil G, Mhatre P. A
randomized, crossover study to determine
bioequivalence of two brands of
dexibuprofen 400 mg tablets in healthy
Asian adult male subjects of Indian
origin, Int. J. Clin. Pharmacol. Ther.
;46:48-54.
Eller N, Kollenz CJ, Schiel H, Kikuta C,
Mascher H. Pharmacokinetics of
dexibuprofen administered as 200 mg and
mg film-coated tablets in healthy
volunteers. Int. J. Clin. Pharmacol. Ther.
;36:414-417.
Seo-Ryung Kim, Jin-Ki Kim, Jeong-Sook
Park, Chong-Kook Kim. Dry elixir
formulations of dexibuprofen for
controlled release and enhanced oral
bioavailability. Int. J. Pharmaceut.
;404:2301-2307.
Sadaba B, Campanero MA, Munoz-Juarez
MJ, Gil-Aldea I, García-Quetglas E,
Esteras A, Azanza JR. A comparative
study of the pharmacokinetics of
ibuprofen arginateversus dexibuprofen in
healthy volunteers. European Journal of
Clinical Pharmacology. 2006;62:849-854.
El-Sayed YM, Niazy EM, Khidr SH. Invivo evaluation of sustained release
microspheres of metoclopramide
hydrochloride in beagle dogs. Int.
J. Pharm. Sci. 1995;123:113–118.
El-Said Y, Hashem F . In-vitro evaluation
of sustained-released theophylline tablets.
Dr.Deve. Ind. Pharm. 1991;17281–293.
Higuchi T. Mechanism of sustained action
medication: theoretical analysis of rate of
release of solid drugs dispersed in sold
matrices. J. Pharm. Sci. 1963;52:1145-
Hosny EA, Al-Helw ARM, AlDardiri MA . Comparative study of in vitro
release diclofenac sodium from certain
hydrophilic polymers and commercial
tablets in beagle dogs. Pharm. Acta. Helv.
;73:159–164.
Peppas NA. Analysis of Fickian and
nonfickian drug release from polymers.
Pharm. Acta. Hel, 1985;60:110-111.
