| Cefuroxime, belongs to the second generation cephalosporins, whick is developed andpatented successfully by the British company GlaxoSmithKline, and also appeared as thename as “Zinacef” on the market in the United Kingdom, Ireland, Germany and Italy in1978, then subsequently sold in many countries of the globe. It’s highly stable againstβ-lactamase, has a high activity for most G-and G, safety, and become clinically valuablebroad-spectrum antibiotics.Its gastrointestinal absorption is very less after the oral cefuroxime, according to GSK’spatent4267320disclose, get cefuroxime ester (CefuroximeAxetil, CFA) on the introductionof cefuroxime C4carboxyl ester group, can enhance its lipophilicity and stability in thegastrointestinal tract and greatly improved oral absorption rate. Cefuroxime axetil does nothave antibacterial activity, so the drug is widely applied because of the rapidly generate andhumoral non-specific enzymatic hydrolysis in the blood after oral absorption andantibacterial effect of cefuroxime.Domestic formulations commonly used in clinical cefuroxime axetil are tablets,capsules, granules and dry suspension. Dry suspension plays an integral part in animportant position in clinical application because it is easy to carry, easy to swallow forinfants, children, seniors and other patients with swallowing difficulties, and also with some other advantages. However, cefuroxime axetil has very bitter taste, so dry suspensionmakes a serious impact of patient medication compliance. In regard, this requires the use oftaste masking technology to solve this shortcoming. Taste masking techniques currentlyused with the addition of flavoring agents or sweeteners, pharmaceuticalmicroencapsulation, ion exchange, solid dispersion law, including legal, coating methodssuch as spray drying and so on. But for the above-described medicine, taste maskingmethod is not applicable.Currently we use stearic acid as a taste-masking coating material, the method of tastemasking is that the cefuroxime stearate is mixed together with the stearic acid in the moltenstate, after cooled and crushed into particles having a particle size. But he method can notachieve taste masking requirements due to the destruction of the integrity of the coating.The new technology, hot melt spray coating is now available and has been successfullyapplied to the production of pharmaceutical preparations. Hot melt spray coating is specialcoating method which is uniformly mixed molten materials and other materials into a mistatomizer dispersed droplets at a specific temperature (usually a temperature above themelting point but below the melting point of the hot melt material of other materials) andsufficient contact with the freezing chamber cold air by heat exchange, so that the dropletmist rapid solidification completion in the cyclone gas-solid separator means to obtain afine powder or a special coating of fine particles of semi-finished or finished products.This article is using hot-melt spray technology to produce cefuroxime axetil particlesfor taste masking, and make the particles go through a fluidized bed to produce drysuspension, and the fine particles and other materials prepared by spray dry suspensionthrough a fluidized bed granulation top. This technology is low technical requirements forequipment, operation simple, achieve industrialization continuous production, and also canmask bitterness of cefuroxime ester very well. Dry particulate suspension which isproduced by taste masking cefuroxime axetil particles is blunt convenient, taste good, andpatient compliance is high, especially for infants, children, the seniors and patients takingother swallowing difficulties.In reference to this subject a lot of taste masking technology, hot melt spray aspects of the patent literature, to fully understand the physical and chemical properties of cefuroximeaxetil, analytical methods, and other information on the preparation process, design a seriesof experiments to research a series of parameters of hot melt spray preparation ofcephalosporin octyl furosemide lipid coating materials used for taste masking particles,porogen, and use a series of characterization to evaluate the taste-masking of cefuroximeaxetil particles.The thesis is divided into eight parts:Chapter One: The recent progress of cefuroxime ester, and a brief overview of thestatus of dry suspensions studied.Chapter Two: A brief overview of the experiment principles and hot melt sprayprocess.Chapter Three: Build in vitro analysis method of cefuroxime ester.Chapter4: Preparation of hot-melt spray freeze taste masking of cefuroxime axetilparticles. Including the effects of melt temperature, the lipid to drug ratio of the coatingmaterial, the kind of porogen, preparation and lipid factors porogen ratio of coating material,atomization pressure, the freezing temperature of cefuroxime ester particles and some otherpreparations of factors that affect the taste masking cefuroxime axetil particles.Chapter5: Optimization for the hot melt spray freezing technology which producescefuroxime axetil coated particle formulation.Chapter6: Determination of particle characteristics of cefuroxime axetil.Chapter7: Decide cefuroxime axetil dry suspension prescription process, andinvestigate its quality results of the examinations compliance, taste masking effect is betterthan the commercially available product.Chapter8: Preliminary investigation of the stability of cefuroxime axetil drysuspension. |
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