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Thienopyrimidone-Sulphur-Heterocyclic Compounds-Sulphur.A general survey of the different methods of preparation of thietanes , thiazolidinones , thiazolines , thiazolidines , thiolanes , thiomorpholinones thieno[3,4-d]oxazoles and thienopyrimidones is represented .3- Characterization of the prepared tablets by weight variation, drug content, tablet diameter, thickness, disintegration time, friability and hardness.4- Dissolution studies for the prepared tablets. The method described in the USP XXV was used to study the dissolution characteristics of the prepared tablets.5- The anti-inflammatory activity of the prepared rofecoxib tablets (formula No. 3), showing the highest in-vitro release rate was determined using paw edema method in rats.The obtained results indicated that:1- The physicochemical properties of the prepared tablet comply with the USP XXV pharmacopoeial requirements.2- Direct compression technique can be used successfully for the preparation of rofecoxib tablets, and has better dissolution characteristics for the drug over the tablets prepared by wet granulation technique.3- Tablets containing co-ground mixture of rofecoxib with PVP 40000 or Avicel pH 101 and Sta-Rx starch as filler (formula 2, 3) gave the fastest dissolution rate among the other prepared tablets.4- There is a significant difference in the anti-inflammatory effect between the prepared rofecoxib tablets and the commercially marketed rofecoxib tablets.Chapter 4Formulation and evaluation of rofecoxib suppositoriesThe aim of this work in this chapter was to formulate rofecoxib suppositories dosage forms. Suppositories were produced using both fatty, amphiphilic and water soluble suppository bases.The work in this chapter includes the following:1- Preparation of rofecoxib suppositories in fatty bases namely; cocoa butter and witepsol E75.2- Preparation of rofecoxib suppositories in amphiphilic bases namely; suppocire AM and suppocire CM.3- Preparation of rofecoxib suppositories in water soluble bases; mixtures of PEGs with different molecular weight and weight ratios.4- Preparation of rofecoxib suppositories containing co-ground mixtures of the drug with either PVP 40000 or Avicel pH 101 in a ratio 1:5 w/w, using cocoa butter and witepsol E75 as suppository bases.5- Preparation of rofecoxib suppositories containing non-ionic surfactants namely; Tween 80, Brij 58 or Myrj 52 in different concentrations, using cocoa butter and witepsol E75 as suppository bases.6- The prepared suppositories were produced by fusion method, and evaluated with regard to drug content, uniformity of weight, disintegration time as well as the other physical parameters such as appearance, melting range and breaking test.7-Dissolution studies of rofecoxib from the prepared suppositories were carried out using XXV dissolution procedures in phosphate buffer of pH 7.4.8- The anti-inflammatory activity of rofecoxib in the prepared rofecoxib suppositories, according to maximum release rate of the drug, formula No. 2. (PEG 6000: PEG1000; 75:25%w/w), and formula No.29. (Cocoa butter containing 10% Tween 80 % w/w), was carried out on the caragenin induced paw edema in rats.The obtained results revealed that;1- The nature of the suppository bases and its nature affect rofecoxib release.2- The tested suppository bases can be arranged according to their rofecoxib release as follows: PEGs > cocoa butter > witepsol E75 > suppocire AM > suppocire CM.3- Suppository base composed of PEG1000: PEG6000 (25: 75 %w/w) provided the highest drug release (92%).4- Incorporation of rofecoxib in the form of co-ground mixture improves the drug release from fatty suppository bases. The highest drug release was obtained from cocoa butter suppository base containing co-ground with PVP 40000.5- The used non-ionic surfactants can be arranged according to the percentage of rofecoxib released as follows: Tween 80 > Brij 58 > Myrj 52.6- The incorporation of 10%w/w tween 80 in witepsol E 75 and cocoa butter suppository bases led to increase the percentage of rofecoxib released (92.6 and 89.01% respectively), while (12.7 and 14.5% of the drug respectively, was released from the same suppository bases without Tween 80.Part ΙΙΙStability studies of rofecoxib in certain prepared pharmaceutical dosage formsIn this part, the following stability studies were carried out;1- Effect of aging (shelf-storage):The selected formulae of the prepared rofecoxib capsules and tablets were stored at room temperature. The selected formulae of the prepared rofecoxib suppositories were stored at room temperature and in a refrigerator. The drug content was determined after storage for 15, 30, 60, 90, 120, 150 and 180 days.2- Accelerated stability testing:The selected formulae of the prepared capsules and tablets were stored at 3 temperatures 30, 37 and 45ºC for six months and 75% relative humidity. The drug content was determined at the beginning of the test and after storage for 15, 30, 60, 90, 120, 150 and 180 days using HPLC and TLC techniques.The results indicated that the selected formulae of the prepared rofecoxib dosage forms were stable under the previous conditions after six months.
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