A Study On Preparation Of Bilayer-core Osmotic Pump Tablets Exempt From Laser Drilling

Osmotic pump tablet had the advantages like releasing drug at an approximately constant rate up to 24 h;releasing drug independent on physiological environment in gastrointestinal tract;exhibiting comparable in vitro/in vivo drug release,was considered as the ideal oral dosage forms up to now.Among various kinds of osmotic pump tablet,by employing an expanding layer,the bilayer-core osmotic pump tablet was able to deliver water-insoluble drugs much more closely to zero-order and could achieve a higher release percentage at 24 h.However,a laser drilling device with the function of drug layer identification must be used in the traditional preparation of bilayer-core osmotic pump tablet.These kind of imported devices were very expensive.Although domestic devices had been developed,the efficiency and reliability of laser drilling were not satisfactory.The industrialization of osmotic pump tablet was restricted by the laser drilling device.In this paper,the water-insoluble drug nifedipine was used as the model drug. The core tablets with an indention on the drug layer surface were compressed by a punch with a needle by us.The processes of drug layer identification and laser drilling were eliminated by coating the indented core tablets and then the osmotic pump tablet was achieved.Based on the preliminary study,the main factors which affected on the drug release were set as:A.NaCl amount in drug layer;B.PVPk90 amount in drug layer;C.CCMC-Na amount in push layer;D.NaCl amount in push layer.The formulation of nifedipine bilayer-core osmotic pump tablet was optimized according to L₉(3⁴)orthogonal design.The in vitro release tests were carried out and evaluated by similarity factor(f₂).The optimal formulation was found as:nifedipine:30.0 mg; NaCl in drug layer:60.0 mg;PVPk90 in drug layer:80.0 mg;CCMC-Na in push layer:50.0 mg;NaCI in push layer:50.0 mg;MCC in push layer:30.0 mg.The effect of membrane thickness and PEG400 level,agitation rate and release media on drug release was also investigated.The thickness and PEG400 level of membrane were important effective factors on drug release.The increase of PEG400 level can increase the membrane permeability and drug release rate.The thickness of membrane could change the speed of water imbibing,resulting in the drug release rate variation.The prepared bilayer-core osmotic pump tablet could deliver nifedipine at an approximate constant rate over 24 h independent of the agitation rate and release media and a satisfactory controlled release effect was achieved.The processes of drug layer identification and laser drilling in traditional preparation of bilayer-core osmotic pump tablet was eliminated by coating the indented core tablet.By employing this method,the preparation process was simplified and the cost of preparation was cut down.It may be promising in the field of preparation of osmotic pump tablet.A power calibration equation,y=ax^b,was attempted to calibrate the standard curve with data obtained by high performance liquid chromatograph by employing nifedipine as the model drug and evaluated by comparing with the traditional linear calibration equation.It showed that the inaccuracy of linear calibration equation increased when the concentrations decreased.The traditional linear equation was not suitable to be used in relatively low concentrations in broad concentration range. Different from the linear equation,the power equation fitted very well in all data points in broad concentration range.