الفهرس 
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Abstract
Background: Oral drug delivery is among the various routes of drug administration, being the most preferred. Most sustained release dosage forms are designed with the intention of the administration of a single dosage to provide immediate release of an amount of the drug that immediately produces the required therapeutic effect. In-situ gel drug delivery system has inaugurated a new transom as a “smart carrier” in oral drug delivery system. It has been extensively recommended for sustained drug delivery. Objectives: Increase the solubility of Gmp (BCS II) through using a pH modifier and sustain its release using oral in-situ gelling system with pH modifier. Also, Preparation of ZT (BCS III) in nanostructured lipid carrier for dual tackling of its first pass metabolism and low permeability. Similarly, dispense the lipid particles in oral in-situ gelling system to sustain the effect of ZT. Methods: preparing new in-situ gelling tablet matrix of Gmp using two nontoxic and biodegradable biopolymers from animal origin namely, chitosan (CT) and casein (CA) in different ratios together with the basic tromethamine (Tris) as a pH modifier then evaluating the prepared tablets with respect to physical properties, in-vitro release, stability and in-vivo study. preparation of ZT loaded NLC system and applying quality by design approach to study the main effects and interactions of the critical process parameters namely; Gelucire amount, Labrasol volume nd concentration of chitosan solution on the critical quality attributes namely; % EE, % yield, particle size and PDI. Besides, dispending the optimum ZT NLC in in-situ gelling hard gelatin capsule to sustain its release and carry out the pharmacodynamic study using mice. Results: The higher the ratio of CA in the tablet matrix, the lower its swelling index and the higher its viscosity, indicating a shear thickening property. Intuitively, zero order drug diffusion in 0.1 N HCl prevailed for 8 h. Both reduction of blood glucose level up till 11 h and X-ray imaging of the selected tablets in the GIT of rabbits correlated well with the shear thickening properties. NLCs formula (F8) which was prepared by using the low level of both Gelucire and Labrasol, and high level of concentration of chitosan solution showed the highest %EE, %yield besides low particle size and PDI. Moreover, whether free ZT or ZT in NLC formulated in in-situ gelling hard gelatin capsules, the drug release was sustained. Nevertheless; the NLCs experienced more sustainable effect. Dispending NLC in in-situ gelling hard gelatin capsule was found to significantly improve the therapeutic efficacy of ZT by reducing the number of writhings in mice. Conclusion: Gmp in-situ gelling tablet encompassing Tris as a pH modifier may be considered promising in solving the problems that may be encountered with poorly soluble (class II) drugs with irregular therapeutic effects as well as other weakly acidic drugs with narrow absorption window. ZT loaded NLC in in-situ gelling hard gelatin capsule may be considered as a promising formula in ameliorating poor permeability and bypassing the pre-systemic metabolism of (class III) ZT or similar drugs with the same ailments through lymphatic absorption.