Pulsatile Release Tablets Research Articles

Formulation Approach for Nicorandil Pulsatile Release Tablet

The purpose of this study was to obtain a nicorandil pulsatile release tablet that has a well-regulated release lag time. When nicorandil is used as an antiangina drug, administration time control is important. A pulsatile release tablet is one of the effective approaches to modified release to reduce daily administration frequency. In this study, a pulsatile release tablet of nicorandil was formulated by fumaric acid dry coating around the core tablet including nicorandil. The model tablets, which had different content ratios of excipients in the dry-coating layer, were characterized by a dissolution test. The results showed that the release lag time was generated with fast release profiles. Various lag time controls of tablets were achieved, from 60 to 310 min on average, by variation of outer layer composition. From an analysis of the relation between lag times and outer layer composition, the key ingredient for prolongation of lag time was found to be fumaric acid. To analyze the lag time generation mechanism, water penetration for tablet was measured. The results indicated that the penetration depth was proportionate to the square root of time and the lag time formation mechanism was simple water penetration through the matrix of fumaric acid to the tablet core. The results also showed that the Washburn equation could be used to design the lag time of the pulsatile release tablet in this study. In conclusion, novel release control technology using fumaric acid was appropriate to obtain a nicorandil pulsatile release tablet that has well regulated lag time.

Development and Mathematical Simulation of Theophylline Pulsatile Release Tablets

ABSTRACTTheophylline pulsatile release tablets consisting of a fast-swelling core with a water-insoluble ethylcellulose were developed. Effects of coating material, the amount of the plasticizer, subcoating, the type of the disintegrant, and coating level on the release profiles were investigated. Results showed that ethylcellulose was the best candidate polymer for pulsatile release tablets. Rupture time increased with increasing the amount of the plasticizer, but 15% plasticizer provided the best release profiles. Tablets with Methocel® E50 as subcoating was most optimal in order to achieve a long lag time and followed by a rapid release. The lag time of tablets containing different disintegrants increased in the following order: croscarmellose (Ac-Di-Sol®) < sodium starch glycolate (Explotab®) < low-substituted hydroxypropyl cellulose (L-HPC) < crospovidone (Kollidon® CL). And the rupture time increased with higher coating level. A mathematical model was presented to predict the lag time prior to rupture. Results of the water uptake experiment were used to estimate the apparent diffusion coefficient of the coating tablets. The prediction of the lag time based on the presented model is in good agreement with the experimental results.

Development of pulsatile release tablets with swelling and rupturable layers

A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as pulsatile drug delivery system. Cores containing buflomedil HCl as model drug were prepared by direct compression of different ratios of spray-dried lactose and microcrystalline cellulose and were then coated sequentially with an inner swelling layer containing a superdisintegrant (croscarmellose sodium) and an outer rupturable layer of ethylcellulose. The effect of core composition, level of swelling layer and rupturable coating, and magnesium stearate in rupturable layer was investigated. Mechanical properties of ethylcellulose films in the dry and wet state were characterized with a puncture test. Rupture and dissolution tests were performed using the USP XXIV paddle method at 50 rpm in 0.1 N HCl. The lag time of the pulsatile release tablets decreased with increasing amount of microcrystalline cellulose in the cores and increased with increasing levels of both swelling layer and rupturable ethylcellulose coating. Increasing levels of the ethylcellulose coating retarded the water uptake and thus prolonged the lag time. Addition of magnesium stearate to the ethylcellulose coating lowered the mechanical strength of the film and improved the robustness of the system.

An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets

To develop new pulsatile release tablets, which can suppress drug release in stomach and release the drug rapidly after a predetermined lag time of about 3 h in intestine, the use of tablets with ethylcellulose/Eudragit L as a coating film and cross-linked polyvinylpyrrolidone in the core tablets was investigated. The release of diltiazem hydrochloride (DIL) as a model drug in the core tablets was investigated in vitro. The lag time ( t 10) was prolonged with an increase of the coating level, whereas the drug release rate was almost constant, irrespective of the coating level. The water-uptake study and electron microscope photographs suggested the mechanism of pulsatile release of drug. Pulsatile release tablets containing 60 mg DIL with 4.4 h of lag time ( t 10) in vitro were administrated to eight volunteers. The mean plasma concentration curves showed 4.9 h of lag time ( t lag), 8.0 h of time to maximum concentration ( t max) and 3.1 h of time between t max and t lag ( t psi) in vivo. Relative bioavailability was 1.05 for pulsatile release tablets compared to conventional tablets.

Absorption of Diltiazem in Beagle Dog from Pulsatile Release Tablet.

An orally applicable pulsatile drug delivery system in dry-coated tablet form was prepared using diltiazem hydrochloride as the model drug, and a polyvinyl chloride-hydrogenated castor oil-polyethyleneglycol mixture as the outer shell of the tablet. In vitro drug release from the prepared tablet exhibited a typical pulsatile pattern with a 7 h lag phase (non-drug release period). This dosage form was orally administered to three beagle dogs under non-fasting and fasting conditions, and the plasma concentration level of diltiazem was determined according to time after administration. The result of the in vivo study in non-fasting dogs suggested that the drug could be released in the gastrointestinal tract as in the in vitro test. However, under the fasting condition, a large difference in the plasma concentration profile was found, suggesting that the disintegration time of the tablet tended to be influenced by the feeding condition of subject.

Design and preparation of pulsatile release tablet as a new oral drug delivery system.

To achieve time-controlled or site specific delivery of a drug in the gastrointestinal tract, an orally applicable pulsatile drug release system with the dry-coated tablet form was developed. The system consisted of a less water permeable outer shell and a swellable core tablet; from such a system, the drug was expected to be rapidly released after a certain period of time on the basis of time-controlled disintegration mechanism. Various model disks of outer shell, consisting of hydrogenated castor oil and polyethyleneglycol 6000, were tested for their water penetration rate. The experimental results showed that water penetration proceeded obeying the boundary retreating mechanism, so that the lag time of the system could be controlled by changing either the thickness or the composition of the outer shell. The swelling force of various commercially available disintegrants was quantitatively compared, and it was found that carboxymethylcellulose calcium was the preferable disintegrant to be used for the core tablet. On the basis of the results of a series of fundamental studies, various pulsatile release tablets of isoniazide with different lag times were designed. In the in vitro dissolution test, typical pulsatile release was achieved for all the tablets prepared, and a good correlation was found between the observed lag time and the estimated lag time calculated from an empirical equation deduced from the thickness and polyethyleneglycol 6000 content of the outer shell.