Acta Pharm. 62 (2012) 71-82
Original research paper
Eudraginated polymer blends: A potential oral
controlled drug delivery system for theophylline
MARTINS
EMEJE, LUCY JOHN-AFRICA, YETUNDE ISIMI,
OLOBAYO KUNLE and SABINUS OFOEFULE
1 Department
of Pharmaceutical Technology and Raw Materials Development, National Institute
for Pharmaceutical Research and Development (NIPRD), Abuja, Nigeria
2 Department
of Pharmacology and Toxicology, National Institute for Pharmaceutical Research
and Development (NIPRD), Abuja, Nigeria
3 Department of Pharmaceutical Technology and
Industrial Pharmacy, University of Nigeria, Nsukka, Enugu state, Nigeria
Accepted November 28, 2011
Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl®) formulation. Asmanyl® tablets showed faster absorption (tmax 4.0 h) compared to the TPH formulation, showing a tmax value of 8.0 h. The cmax and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl®, revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.
Keywords: theophylline, polymer blends, modified release, in vitro release, in vivo release