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    Physiochemical and drug release properties of liquisolid formulations in comparison to their physical mixture counterparts

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    Authors
    Bello, Hussaini
    Issue Date
    2018
    
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    Abstract
    Various techniques have been used for modifying the release properties of drugs over the past years. Techniques such as liquisolid technology have raised a lot of interest in many researchers which can be employed to enhance or sustain dissolution. Various liquisolid (LS) tablets of diltiazem containing Polysorbate 80 as a non-volatile solvent for sustained release were prepared. PolyoxTM is an attractive pharmaceutical polymer used in controlled release dosage forms mainly because of its insensitivity to the pH of the biological medium and ease of production. The aim of this study was to investigate the influence of several formulation factors i.e., the PolyoxTM grade at different molecular weight (MW), PolyoxTM particle size and ratio, the AEROSIL® grade, the use of diluent, polymer type and the drug type as well as their interactions on drug release from LS formulation in comparison to their physical mixture (PM). The result showed that PolyoxTM MW was a key determining step in achieving sustained release, with the higher MW of PolyoxTM resulting in a more delayed release profile. The delayed DTZ release could be related to the rate and extend of hydrogel formation on the tablet surface. The P–CMRs and net–CMRs of both LS and PM formulation powders also showed increasing trends with increasing the MW of PolyoxTM. The release of DTZ from both LS and conventional tablets showed mostly decreasing trends with increasing PolyoxTM concentration and decreasing PolyoxTM particle size distribution. This could be attributed to the formation of stronger and thicker gel layers on the tablet surfaces in the case of higher concentrations of PolyoxTM. The results also showed LS tablets to produce slower release of drug than their PM counterparts, regardless of PolyoxTM particle size. The release profile of the DTZ from both LS tablets and their counterpart PM tablets showed decreasing trends with increasing the surface area of hydrophilic AEROSIL® (from 65 m2/g to 225 m2/g). This could be due to the higher tensile strength (TS) of the tablets containing AEROSIL® particles with higher surface area compared to those prepared using AEROSIL® particles having lower surface areas. Also, the result showed that comparing the different diluents showed that hydrogenated vegetable oil (HVO) provided the slowest release pattern of DTZ across diluents used in both the LS compacts and PM tablets. This could be attributed to hydrophobicity imparted by HVO to matrix system when in contact with aqueous medium it takes a longer time to penetrate into the tablet. Drug release from LS tablets was affected by the polymer type. The release was in the order: Eudragit® RL < Eudragit® RS < Hypromellose < PolyoxTM < Psyllium. Hydrophilic Psyllium provided a slowest DTZ release across the different polymers used in the preparation of both the LS and PM compacts. The incorporation of Psyllium into PolyoxTM further elicited a decrease in drug release rate from individual polymer matrices. This was ascribed to the reduced entrance of aqueous media into the matrix due to the presence of the stronger viscose gel within the two hydrophilic matrices compared to individual Psyllium and PolyoxTM. The ratio between PolyoxTM and Psyllium has critically influenced diltiazem release profile. The results showed that matrices containing (Psyllium:PolyoxTM) at 1:1 ratio can slow down the drug release more than the matrices compacts containing 1:3 and 3:1 (Psyllium:PolyoxTM) ratio. The results also suggest that the ii combination of PolyoxTM and Psyllium at 1:1 ratio showed robust dissolution against pH and rotational speed and therefore indicates an appropriate sustained-release profile. The dissolution rate of PolyoxTM:Psyllium from different pure drugs showed a decreasing trend with an increase in their solubility. The solid state analysis studied in this work confirms the presence of a fraction of the drug mass in a solubilised state within polysorbate 80 in LS powders. Regardless of all variables used in this study, LS formulations showed slower drug release than their PM counterparts. In conclusion, the mechanical properties of LS formulation are poor in comparison to their counterpart PM. Therefore, further work is required to improve the hardness of LS tablet comprehensively.
    URI
    http://hdl.handle.net/2436/621794
    Type
    Thesis or dissertation
    Language
    en
    Description
    A thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of Philosophy (PhD).
    Sponsors
    Tertiary Education Trust Fund (TETFUND)
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    Theses and Dissertations

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