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Keywords: Applied Sciences
Medicine & health
Human anatomy,cytology & histology
Pharmacology & theraputics
Issue Date: 2015
Publisher: Gomal University, D.I. Khan, Pakistan
Abstract: The main objective of this research task was to accomplish successfully development of the controlled release matrices of Flurbiprofen and ibuprofen. These both are typical members of NSAID’s and offer considerable therapeutic effects to relieve the symptoms and subsequent management of chronic inflammatory disorders such as osteoarthritis, Rheumatoid arthritis, ankylosing spondylitis and dysmenorrhea. Eudragit polymers were employed as rate controlling agents and consequently, their obvious impact on kinetic, mechanism and pattern of drug release was investigated. This highly skillful task did require primarily, initial preformulation studies to rule out drug identification, as well as solubility profiles. The drug and polymer as well as drug, polymer and co excipients compatibilities were also seriously addressed. Different codes were used to produce a set of formulations involving Eudragit L 100, L 55 and S 100 respectively by employing different drug to polymer ratios for both Flurbiprofen as well as Ibuprofen without any further addition of co-excipients. Moreover, same formulations were also developed in which primary filler (lactose) was partially replaced with co–excipients such as starch, CMC, HPMC, Gum Acacia and Gum tragacanth respectively. Ultimately the impact of these co–excipients upon drug release from fabricated matrices was also noted. Official procedures were employed to describe the Micromeritics studies of pure drugs a s well as respective physical mixtures of the formulation. The results provided puzzling statements about the flow of the pure drugs describing poor flow behavior. This problem was rectified by developing physical mixtures of different ingredients including magnesium stearate as a result, an enhanced and improved flow properties were exhibited. This was indispensable and prominent step in tablet preparation. Direct compression method was adopted as preferred procedure to get matrix tablets. Matrix tablets formed under such a tidy situation under go physico-chemical assessment according to official procedures. These test protocols included dimensional, friability, hardness, weight variation and content uniformity tests. All these searching checks were within official limits. In–vitro dissolution tests were performed for matrix tablets by selecting rotating basket method (USP method 1) with ix phosphate buffer of PH 7.4 as recommended dissolution medium. Matrices having Eudragit L- 100 enhanced the drug release more efficiently as compared to other grades. The leading factors affecting rates and kinetics of drug release from matrices included particle size, drug to polymer ratio and viscosity grades. Various co–excipients incorporated due to progressive replacement of lactose (Primary filler) such as CMC, HPMC, Starch, Gum Acacia and Gum Tragacanth caused enhanced drug release i.e within 3-5 hours. Different kinetic models were fitted to the data of drug release from the matrices. Korseymerpeppas equation best fitted the release profile from matrices by giving “n” value that described anomalous non fickian release mechanism for formulations without co-excipients. The similarity factor (f2) was also determined by comparing dissolution profile of both matrices and conventional dosage forms. The optimized formulations of both drugs were selected by keeping in view description of kinetic models as well as in-vitro dissolution profiles. The optimized formulations were subjected to stability testing in accelerated condition for short term exposure and they offered good stability profiles in accelerated conditions. The optimized tablets were also selected for in-vivo studies to determine in-vivo bioavailability and pharmacokinetic parameters in rabbits. The result deduced, showed test formulation to display extended drug release as compared to reference formulations. Also the test formulations portrayed good linear relationship between in-vitro drug release and in-vivo drug absorption.
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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