Preparation of the Indomethacin–CCC (IMC–CCC) and IMC–CCC–LA MixtureĪ binary mixture of various weight ratios of IMC/CCC were prepared (1:99, 2:98, and 5:95 % w/ w) by dissolving 0.5 g of each ratio in 10 mL of chloroform. It is expected that such a formulation would improve IMC stability, allow for a suitable release process and enhance its ability to permeate the skin barrier. The aim of this study was to prepare IMC in an effective transdermal preparation. In addition, such a thermotropic liquid crystal may protect the drug molecule from light. The CCC should also enhance the ability of IMC to cross the stratum corneum. If a drug can be incorporated into its normal cubic phase then encapsulated IMC may improve its stability. According to the chemical properties of cholesteryl cetyl carbonate (CCC), it is a thermoresponsive material ( 23, 24). In this study, we employed CCC (a cholesterol derivative) as an excipient for a transdermal formulation. The liquid crystal materials used in topical/transdermal formulations are those such as cholesteryl oleyl carbonate ( 21) and glyceryl monooleate ( 19). Liquid crystals may serve as a thermoresponsive membrane to control drug release ( 21, 22). Therefore, the development of liquid crystals as an aid for drug delivery systems is expected to increase the efficiency of the drug by increasing its stability and absorption ( 20). This is because such phases are thermodynamically stable, and materials can be stored for long periods of time without phase separation. In the cosmetic and chemical industries there have been interests in forming liquid crystalline phases for delivery systems ( 18) and this is now being exploited in the field of pharmacy ( 19). A liquid crystalline gel was used to control release of the IMC sodium salt, only 19 % was obtained in 24 h ( 15). Phosphatidylcholine was used as a permeation enhancer of IMC ( 17). For instance, IMC was incorporated into a microemulsion that controlled its release ( 16). Several types of IMC formulations have been investigated. However, facilitating the cutaneous absorption of IMC is not sufficient because its release from such formulations may be limited ( 15), together with its ease of hydrolysis and lack of stability ( 12). A transdermal preparation must not only have an ability to facilitate the penetration of the drug into a painful area, but must also be devoid of any negative cutaneous reaction and must also be easy to apply. Transdermal formulations may be another solution for improving IMC biovailability. In view of these problems, it is important to devise strategies to tackle them. Various methods have been employed to enhance the drug stability in aqueous solvent systems such as by encapsulation in liposomal suspensions, complexation of the drug with various cyclodextrins ( 11), entrapment into multilamellar liposomes ( 12), the synthesis of an ester prodrug ( 13) and using spray-dried nanocapsules and nanospheres ( 14). In aqueous solutions, IMC is degraded and its therapeutic activity is impaired. Numerous efforts have been made to modify the drug dissolution rate ( 7– 10). IMC is practically insoluble in water ( 5) with a partition-coefficient in octanol/water of 3.95 ( 6). In severe situations, it may lead to perforation of the intestine ( 3, 4). IMC may cause or worsen stomach ulcers or intestinal bleeding. The most common side effect of IMC is gastrointestinal irritation. Indomethacin (IMC) is a non-steroidal anti-inflammatory drug that reduces fever, pain and inflammation ( 1, 2).
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