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أستاذ المادة ظافر قحطان سعيد الامين الماشطة
5/28/2011 1:18:06 PM
Monomolecular inclusion compounds:
Cyclodextrins
Monomolecular inclusion compounds involve the entrapment of a single guest molecule in the cavity of one host molecule. Monomolecular host structures are represented by the cyclodextrins. These compounds are cyclic oligosaccharides containing a minimum of six D-glucopyranose units attached by ?-1,4 linkages. Their ability to form inclusion compounds in aqueous so¬lution is due to the typical arrangement of the glucose units, (see Figure 1l-3d) where the cyclodextrin structure forms a torus or doughnut ring which can accommodate molecules such as mitomycm C to form inclusion compounds (Figure 11-5&). The interior of the cavity is relatively hydrophobic because of the CH2 groups, whereas the cavity entrances are hydrophilic owing to the presence of the primary and secondary hydroxyl groups. Some drugs may be too large to be accommodated totally in the cavity.
Cyclodextrins are studied as solubilizing and stabilizing agents in pharmaceutical dosage forms. Cyclodextrins was used to trap, stabilize, and solubilize sulfonamides, tetracyclines, morphine, aspirin, benzocaine, ephedrine, reserpine, and testosterone. The aqueous solubil¬ity of retinoic acid (0.5 mg/liter), a drug used topically in the treatment of acne, is increased to 160 mg/liter by complexation with ?- cyclodextrin. Dissolution rate plays an important role in bioavailability of drugs, fast dissolution usually favoring ab¬sorption. Thus, the dissolution rate of famotidine, a potent drug in the treatment of gastric and duodenal ulcers, and that of tolbutamide, an oral antidiabetic drug, are both increased by complexation with ?-cyclodextrin.
Cyclodextrins may increase or decrease the reactivity of the guest molecule depending on the nature of the reaction and the orientation of the molecule within the cyclodextrin cavity. Thus, ?-cyclodextrin tends to favor pH-dependent hydrolysis of indomethacin in aqueous solution, whereas ?-cyclodextrin inhibits it. Unfortunately, the water solubility of ?-cyclodextrin (1.8 g/100 mL at 25°C) is often insufficient to stabilize drugs at therapeutic doses, and is also associated with nephrotoxicity when cyclodextrin is administered by parenteral routes. The relatively low aqueous solubility of the cyclodextrins may be due to the formation of intramolecular hydrogen bonds between the hydroxyl groups, which pre¬vent their interaction with water molecules.
Derivatives of the natural crystalline cyclodextrins have been de¬veloped to improve aqueous solubility and to avoid toxicity. Partial methylation (alkylation) of some of the OH groups in cyclodextrins reduces the intermolecular hydrogen bonding, leaving some OH groups free to interact with water, thus increas¬ing the aqueous solubility of cyclodextrins. Amor¬phous derivatives of ?-cyclodextrin and ?-cyclodextrin are more effective as solubilizing agents for sex hormones than the parent cy¬clodextrins.
المادة المعروضة اعلاه هي مدخل الى المحاضرة المرفوعة بواسطة استاذ(ة) المادة . وقد تبدو لك غير متكاملة . حيث يضع استاذ المادة في بعض الاحيان فقط الجزء الاول من المحاضرة من اجل الاطلاع على ما ستقوم بتحميله لاحقا . في نظام التعليم الالكتروني نوفر هذه الخدمة لكي نبقيك على اطلاع حول محتوى الملف الذي ستقوم بتحميله .
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