Study The Nature Of The Powder Compression And Gastric Floating Tablets In The Preparation Of Applications

Relatively speaking, the preparation of monolayer gastric-floating tablets using HPMC as main excipients is less difficult to implement in industrial practice, whether in the aspect of cost control or in view of the complexity of preparation procedure. However, the classical method of trial and error was not a feasible way to find out optimal formulation in order to achieve predetermined goal without key parameters in mind which must be controlled at a specific range, especially when the principle agent is hard to be compacted and the ratio of excipients is relatively lower.Both trimbutine maleate (TM) and Panax Notoginseng power, which served as model drugs in this study, are difficult to be compacted. Under the constraint condition that the ratio of all excipients is about 50%, gastric-floating tablets were successfully prepared, which can start to float at once when dropped into artificial gastric fluid, and dissolution rate met the predetermined requirements. All the study was drawing heavily assistant from the application of MPC-100 and specific program.First of all, the automation of experimental data processing was achieved by programming the specific Excel VBA in order to fully mining the potential of Micro Powder Characterize (MPC-100).The disadvantage of the procedure taking from the instrument can only handle an experiment data document and the sketch of producing is a bitmap document , which followed the inconvenience of carrying out horizontal comparison.The VBA macro procedure only need the original data documents that will need to be contrasted to deposit appointed document, then all the data files are handled automatically. i.e. the implementation of numerical integration of compress curves and the mapping of the diagram data and the correspondent test serial number. When needed, it can immediately carry out plotting after selecting a set of experiment serial number that need to be contrasted. Meanwhile, the accuracy of number integral calculus method was certified and the best experiment dosage was also elucidated in order to avoid blindness of practice.The compressibility of PNP is analogy to that of corn starch, which is prone to causing lamination. Using cetylalcohol ethanol solution as adhesive agent, the compactablity of PNP was improved. Surprisingly, when the ratio of cetylalcohol is less than 30%, the density of PNP tablets is increasing with the augmentation of the ratio of cetylalcohol. Through optimal analysis, the optimal ratio of cetylalcohol to PNP is 5%, which could balance the contradiction between the increasing of density and the compactablity.Taking advantage of two groups of orthogonal experimental design, the influences of all excipients in the formulation were investigated. Hydrophobicity comes to light as a common factor which can integrate the factors of calcium carbonate, magnesium stearate and the specification of hydroxypropylmethylcellulose (HPMC) into more extensive conceptual extent.Compared with sodium bicarbonate, calcium carbonate is hard to solve in water, which has the merit of stabilizing the floating state. HPMC (SH60) is more contributory to remain floating state than HPMC (SH90), whereas it is inclined to step down the speed of staring to float. It is also emphasized that the ratio of HPMC in the formulation need to be up to 30%, or the floating ability would decrease.With using MPC-100, the compressibility of TM, which tends to cause the punch sticking in the die, and relevant excipients, was investigated systematically. The compressibility and compactablity of TM were ameliorated after granulation when povidone’s (PVPk30) aqueous solution is at the ratio of 20% (w/v), which is served as adhesive agent. And more importantly, PVPk30 can also reduce the friction between powders and die lateral wall which has the merit of curtailing the consumption of magnesium stearate, which may decrease the stability of TM. Unexpectedly, it was found that magnesium stearate can also improve powder’s compactablity regardless of its classical role knowing as lubricant.Eventually, the optimal formulation (cPVP: CaCO3: PVP: HPMC (400) : TM =0.6:0.2:0.8:5:6) of TM gastric-floating tables was determined through orthogonal experimental design, where cPVP is used to accelerate the speed of starting to float, whose classical application is used as disintegrant. The tablets can start to float themoment dropped into artificial gastric fluid (37℃), and maintain floating for about 9hours. The dissolution rate of tablets came up to predetermine requirement.(2 hours 30%, 4 hours 50% and 9 hours 80%) The result of curve fitting showed that Higuchi equation is the best equation to simulate the dissolution pattern.