الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Oral drug delivery is one of the most important and commonly used route of drug administration due to its ease of administration, high patient compliance, cost effectiveness, least sterility constraints, and flexibility in the design of dosage form. Poorly water soluble drugs often require high doses in order to reach therapeutic plasma concentrations after oral administration. Thus, low aqueous solubility is considered to be the major problem facing formulation development of new chemical entities as well as generic development. Any drug to be absorbed must be present in the form of an aqueous solution at the site of absorption. In-situ micronization is a technique where micro crystallization and surface modification can be achieved by using hydrophilic polymers which act as stabilizing agents for enhancing wetting properties and stability of the microcrystals. Further, the stabilizing agents prevent the crystal growth behaviour of the microcrystals. In-situ micronization gives more crystalline substances that can reduce the cohesiveness and can improve the flow properties. When a hydrophobic substance is micronized, a hydrophobic surface is formed. In this technique hydrophilic polymers are used as stabilizing agents to enhance the wetting properties and dissolution rate. Surface adsorption of hydrophilic polymers like HPMC and MHEC show Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt. enhanced wetting properties which can there by enhance dissolution rate. In-situ micronization technique has many advantages over other size reduction methods such as it does not require any external processing conditions except mild agitation using magnetic stirrer and less processing time. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.it is classified as class 2 drug in biopharmaceutical classification system (BCS), so the major problem facing any production of oral product containing indomethacin is its low aqueous solubility. Accordingly, the main objective of this study was to investigate the potential of in situ crystallization of indomethacin, in presence or absence of hydrophilic materials, to improve drug dissolution with the goal of developing fast disintegrating tablets. Indomethacin crystals were prepared by bottom up approach. Water containing hydrophilic additive (polymer or/and surfactant) was added to ethanolic solution of indomethacin while stirring. The selected polymers were hydroxylpropylmethyl cellulose E5 (HPMC E5), polyethylene glycol 6000 (PEG6000) and polyvinylpyrrolidone K40 (PVP K40). The surfactants used were Tween80 and Glucire 44/14. The precipitated particles were collected and air dried. Solid state characterizations were performed in Abstract 3 Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt. addition to in vitro release studies in both acidic (0.1 N HCL) and alkaline medium (phosphate buffer pH 6.8). Optimized formulation was selected to develop fast disintegrating tablets. Thermal behavior suggested modulation in crystalline nature with reduction in particle size that was confirmed by X-ray diffraction results. Infrared spectroscopy excluded any interaction between drug and hydrophilic excipients. Drug dissolution in acid media showed slight improve in drug release, while marked increase was observed in the alkaline media. Combination between Tween80 and HPMC (F7) showed the best dissolution parameters with 5-folds enhancement in release efficiency (RE) compared to pure drug. Formula F7 was successively used to formulate fast disintegrating tablets with prompted release of 58% of the loaded dose and RE of 83%. In situ crystallization of indomethacin is a good approach for enhanced dissolution rate with the presence of hydrophilic additives during precipitation process improving the efficiency.