Zero-order release of aspirin and theophylline from novel synthesized methylcellulose succinate and hypromellose glutarate matrix tablets

A goal in the design of an oral controlled drug delivery system include but not limited to maintaining relatively constant drug blood levels for a desired period. Zero-order drug release system is expected to achieve this. Earlier, we reported zero-order drug release in water from novel methylcellulose glutarate matrix tablets (Patel et al., Int. J. Pharm. 2006, 316, 15-21). This research deals with substitution of some of the hydroxyl groups of methylcellulose (MC) and hydroxypropyl methylcellulose (HPMC) with hydrophobic acid derivative such as succinic or glutaric acid. Aspirin and theophylline will be used as model acidic and basic drug to study the drug release profiles from the esterified polymer matrix tablets.;For ester synthesis a definite mass of MC or HPMC and succinic or glutaric anhydride, based on their equimolar ratio dissolved in tetrahydrofuran (THF), were reacted at room temperature for 12 hr in a rotary evaporator. The reaction was also carried out under high frequency sonication for 2 hr. THF was removed under reduced pressure of 150 mm Hg using a vacuum pump, washed twice with THF and the solvent was removed using a vacuum pump. The product was air dried and passed through ;The matrix tablets were prepared at a drug:polymer ratio of 4:1 by wet granulation (isopropyl alcohol) method using the manual tablet compaction machine (Glob Pharma) at 3000 PSI with 0.95 cm standard concave tooling at a tablet weight and a height of 0.346 g and 0.42 cm, respectively. Each tablet contained in mg: 200 active, 50 polymer, 80 lactose, 8 povidon, 4 pruvRTM and 4 talc.;Dissolution studies were conducted using USP dissolution apparatus II (Distek) in 0.9 L medium (water, 0.1 N HCl and phosphate buffer pH 6.8 and 7.4) at 100 rpm. The sampling (5 ml) was done with medium replacement, assaying aspirin and theophylline spectrophotometrically at 265 and 272, respectively. Characterization data of MC-SA and HPMC-GA from the FTIR spectra showed the peaks between 1700 and 1738 cm-1 for both the esters which is indicative of the esterification of MC and HPMC. It represents the vibrational stretching of C=O bonds of the esters. These peaks were absent in MC and HPMC FTIR spectra. The NMR spectra of MCSA and HPMCGA delineated the peaks around 2-4 ppm which represent the protons from --CH2 groups of MCSA and HPMCGA. These peaks were absent in MC and HPMC NMR spectra. % Water uptake showed that at all times the % water uptake by MC-SA and HPMC-GA tablets was lower than that by MC and HPMC tablets respectively. Results demonstrate that esterification had significant diminutive effect on the hydrophilicity and the swelling rate of the polymer.;Dissolution profiles of theophylline and aspirin compacts illustrate that for MC and HPMC matrix tablets, there was a non linear fairly rapid aspirin and theophylline release profiles at all pH values. This can be explained on the basis of fairly rapid water uptake of the matrix tablet due to polymers high affinity with water. On the contrary, there was a zero order drug release profile in the case of MCSA and HPMCGA at all pH values with a correlation coefficient of 0.98. At pH 7.4 there was a small increase in the release rate possibly due to the hydrolysis of the ester. The zero order release profile at a reduced rate from the esters may be explained on the basis of reduction of their hydrophilicity and rigidity as evidenced from their reduced water uptake. This may have contributed to the formation of permeability barrier controlling the drug release rate.;Drug release from MC and HPMC can be prolonged by substitution of free hydroxyl group with ester linkage. Synthesis time for the ester time can be reduced by sonication. The in vitro drug release of aspirin and theophylline at a drug to polymer ratio of 4:1 yielded a zero order release from MCSA and HPMCGA at GI pH values.