SUMMARY AND CONCLUSION

SUMMARY AND CONCLUSION

8 SUMMARY AND CONCLUSIONS In spite of the many challenges faced by researchers while designing an effective, reproducible and stable dosage form, oral dosage forms continued to maintain a prominent position even in 21 ^' century. Improving patient comfort is basic need and a well-known strategy to improve patient compliance. Whatever the oral dosage forms, a special attention is attracted to the class of patient's i.e. children and elderly who has lot of difficulty in swallowing. Hence most of the products for children are formulated in complex dosage forms like syrups or suppositories. It is noted that for essential drugs such as Theophylline and Valporic acid, the exact dose should be administered with SR characteristics to achieve patient compliance and desired therapeutic effects that are not possible with syrups or suppositories. The prepared formulation is convenient dosage form which will improve children comfort and compliance. Among all possible oral SR systems currently in the market, multiparticulates are becoming more and more popular. They offer a convenient form to Pharmaceutical development and attracts the patients. Altogether, it represents one of the most desirable options for a profit perspective. One approach to design oral SR system is to coat drug loaded pellets with a polymer that regulate their drug release rate. Such coated pellets can be filled in hard gelatin capsules or compacted into Multiple-Unit tablets. Such tablets are normally intended to disintegrate in discrete pellets in the gastrointestinal tract and the drug should be subsequently released in a sustained manner from the individual pellets. One challenge in the production of Multiple-Unit tablets is the maintenance of desired drug release after compaction, as the application of compressional pressure can lead to structural changes in the film coating and, consequently, altered drug release. The compression induced changes in the structure of a film coafing can be restricted mainly by controlling the formulation factors, such as type, amount and form of Cushioning Agents, the method of production of pellets, and the type and amount of functional film coating material applied on the pellets. 192

Various fillers were evaluated individually and in combination for providing the Cushioning effect to pellets and developing a tablet with desired characters. It was observed that MCC PH 101 along with lactose monohydrate at 1:1 concentration produces the tablet with desired characters and provides the cushioning effect to the pellets to retain the SR properties. The 40:60 ratio of cushioning agent to pellets provided the Cushioning effect to pellets but failed to produce the tablet with desirable characteristics. Ratio of 50:50 and high of cushioning agent to pellets provided the desired characters to pellets as well as to the tablets that were resultant due to both the plastic deformation and fragmentation nature of MCC and lactose monohydrate respectively. MCC on compaction preferentially get deformed plastically and provides the cushioning effect to the pellets. Further it forms mechanical interlocking to produce the tablet with desired mechanical strength that disintegrate quickly when came in contact with water. Whereas lactose monohydrate on compaction preferentially gets deforms by fragmentation and provides cushioning effect while the weaker bonding in the particles along with MCC provides the desired tablet characters. One potential problem that was believed to be due to the incorporation of cushioning agents in powder form is segregation, owing to the difference in particle size. But the content uniformity studies of tablets revealed that at 60:40 ratio of powdered cushioning agent to pellets, no segregation was possible which may be due to the percolation theory of powders. Whereas, the newer sophisticated felling techniques can manage the segregation problem if any. Tablets prepared by using cushioning agent as granule or soft pellet form, was unable to cushion the pellets and provide the desired characters to the tablets. It may be due to the interruptions in the transmission of compressional forces from the surface of pellets. Functional film coating materials on the pellets also influences the release of drug after compression. It was revealed in the study that cellulosic coating materials were unable to resist the compressional forces whereas methacrylic co-polymers resist the forces. Further more aqueous dispersions of methacrylic co-polymers showed high resilience as that of cellulosic materials thereby providing resistance from destructive compressional forces. The aqueous dispersions because of their flexibility attain the deformed shape of pellet and thus preventing damage to the coating. The coated pellets at high concentration of coatings increases the resistance to compressional changes. 193

High dose drugs are poor candidate for SR drug delivery system due to its bulky size. Disintegrating Multiple-Unit tablet provides a resource to deliver high dose drugs like Metformin in SR form, by disintegrating the high size tablet containing SR pellets of drug in-vitro in water just before swallowing. Complete emptying of pellets from container into mouth which is needed that can be achieved by forming uniform dispersion of multiparticulates in-vitro. Viscosity modifiers were added to achieve dispersion of pellets in the vehicle. The studies showed that addition of water should disintegrate the tablet instantaneously to liberate the pellets thereafter increasing the viscosity of preparation. This can be achieved by using viscosity modifiers in granule form containing MCC. The powdered form of viscosity modifier forms a swollen layer along the tablet and prevents further penetration of water in the tablet thereby retards the disintegration of tablet. Whereas granule form of viscosity modifiers get liberated after disintegration of tablet that then disintegrate due to MCC to liberate small particles of viscosity modifier and increases the viscosity of dispersion to the desired level. It was also observed that CMC sodium at 01 % concentration was able to increase the viscosity in the desired range quickly. In the present study the preparation of disintegrating Multiple-Unit tablets along with combination of drugs with different release characteristics has been investigated with the intension of gaining a deeper understanding of some of the factors that influences the properties of pellets and tablets. In particular, the compression behavior of pellets constituting the tablets and the consequent effect on the drug release was studied. The solid dosage forms increases the stability of drug products whereas preference of liquefied preparations among pediatric and geriatric patients could substantially increase patient compliance. SR disintegrating Multiple-Unit tablet dosage forms possess the advantages of both the systems as well as the efficacy and accuracy of dosage administration is possible. Although this category of dosage form is still considered to be in its infancy, the trend towards multiparticulate tablet preparations and the necessity of liquefied dosage forms for specific patient groups will ensure increasing growth in the development and application of this type of dosage form. The prepared dosage form was satisfactory and acceptable as it disintegrate rapidly to liberate the intact individual pellets. Photomicrographs showed 194

that most pellets had undergone a certain degree of deformation on compression without any substantial damage to the SR pellets that was confirmed from the release profile of drug from tablet. The purpose of this study was to produce Multiple-Unit tablets containing the polymer coated pellets while maintaining the same release profile as that of uncompacted pellets. It was concluded from the study that coated pellets would be protected from fracture during compaction by the addition of proper type, form and proportion of cushioning agents, protective SR coating film and method of pellet formation, thereby maintaining the release profile of uncompacted coated pellets. The aim of this study was also to investigate the influence of formulation and process parameters on the tablet properties. Thus from the results it was shown that with careful optimization of formulation variables, it is possible to design a rapidly disintegrating SR Multiple-Unit tablet drug delivery system containing drug combinations for oral administration comprising compacted polymer coated pellets containing high dose drug. The findings of the present study will contribute to the knowledge of the parameters which influence the properties of such disintegrating Multiple-Unit tablets. 195