لخّصلي

The drug concentration of the second drug layer is higher than the first layer, and therefore ascending release can be achieved through the drug concentration gra- dient. Initially the drug contained within the first compartment is released, and once the majority of drug from the first com- partment has released, the drug within the second compartment begins to release at an ascending rate (7). The ascending release and delayed sustained-release PPOP show great advantages for achieving stable and slow drug release rates, for avoiding high initial plasma concentrations to remain effective and safe, and also for maintaining a controlled and prolonged treatment window, which reduces adverse effects. and improves compliance (8). However, the osmotic pump process is complex, high cost, time-consuming, dangerous of conspicuous burst release, requires cumbersome quality in-

spection, and has strict processes.

Compression coating is an old technique that was first pro- posed by Noyes in an 1896 patent [9]. Although it is an old concept, compression coating is a novel technology for for- mulation of new DDS systems. It has been used in the pharmaceutical field for many purposes, such as separating in- compatible drugs and combining drugs to achieve different therapeutic effects [10], protecting drugs with oxygen labile, acid-labile, light-sensitive or hygroscopic characteristics [11], for delayed release [12], pulsatile release [13], colon-specific release [14], programmable release, to modify pH sensitivity [15,16] and more. This can be achieved as CC tablets possess many characteristics that cannot be matched by general tablets. At the time of administration, the outer component of the CC tablets can distribute on the surface of the intestinal mucosa, and the core components are thus concentrated on the surface of the gastric mucosa, allowing for complete absorption of the drug and improved bioavailability. A better drug release rate can be obtained through the combination of the two differ- ent release rates, to achieve the desired plasma concentration, to maintain a stable, long effective concentration, reduce the toxic effects of drugs, avoid the stimulation of gastric mucosa and other side effects [17]. When sustained-release tablets are formed by pressing on the outer layer, they are more reliable than when directly coating on the surface of the tablet,

Later-drilled delivery

successfully avoiding problems such as drug leakage and other issues caused by uneven coatings. Further, the stability of the drug can be increased by compressing two different compo- nents without mixing. More combinations of controlled release requirements can be met through the technology of CC tablet, and thus can overcome limitations of using single sustained- release pellets, and achieve more requirements during administration. In the CC tablet system, the entire surface of an inner core is completely surrounded by the coating, which is able to delay drug release from the core until the poly- meric coat has begun to erode, dissolve or is removed. For functional coatings, it is typical to use organic solvents, however these processes have a longer production cycle and limited drug loading, and it is desired to reduce environmental impact. Dry powder tablet coating can avoid these drawbacks, can be pre- pared with incompatible compound ingredients, and is much more efficient than solution coating. Thick coatings can be applied rapidly and the coating process is solvent-free, and the process is more desirable to industry because of the simple manufacturing methods. Current commercially available. compression-coated tablets include glipizide marketed tablets (Glucotrol XL, Pfizer of USA), nifedipine controlled release tablets (Adalat, Bayer of Germany), amoxicillin and potas- sium clavulanate compression-coated tablets (Moxicle TM,

Korea) and more. The aim of this work was to design paliperidone compression-coated tablets for ascending release, using HPC and HPMC as the main functional material for control of the release rate. The factors affecting the drug release behavior in vitro were investigated to optimize the formulations. The drug release mechanism of the paliperidone CC tablets was studied by model fitting, as well as uptake and erosion tests. The rate of drug release is dependent on the rate of polymer swelling, the solubility of the drug, and the soluble fraction of the gel matrix over time. As the rate of erosion of the matrix accel- erated, the drug release also presented ascending release. In the later stages of drug release, although the matrix erosion rate slowed, the majority of the matrix had dissolved, thus re- ducing the barrier and so the drug release rate was still increasing. This work can function to establish a foundation. for compression coating technology, and as such is the first one to apply the compression coating technique to obtain ascend- ing release of paliperidone