Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms

In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristic could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet: aminophylline 50 mg, L-HPC and PEG 6000; outer shell: PH-102 : PEG=8 : 2 200 mg) with the timed-release characteristic was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristic in the gastrointestinal tract. The time (t(max)) required to reach the maximum plasma theophylline concentration (C-max) observed after administration of the press-coated tablet was significantly (p<0.05) delayed compared with that observed after administration of aminophylline solution in the control experiment. However, there was no difference in C-max and area under the plasma theophylline concentration-time curve (AUC(0-->24)) between the press-coated tablet and aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.