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Product distribution / selectivity; |
Example 1: PLGA/NMP liquid formulation testing in rat; Poly(dl-lactide-co-<strong>[502-97-6]glycolide</strong>) was prepared via ring opening condensation of dl- lactide and <strong>[502-97-6]glycolide</strong> dimmers. A quantity of the polymer having a 85/15 ratio of lactide to <strong>[502-97-6]glycolide</strong>, a weight average molecular weight (MW) of 23 kDa and a terminal carboxy group was weighed into a glass sovril bottle and a sufficient amount of pre-sterile filtered NMP was added to give a 60:40 weight ratio of polymer to solvent. The mixture was gently stirred with the aid of a magnetic stirrer bar at room temperature until the polymer completely dissolved. The required amount of anastrozole was then added to the polymer solution and the mixture was sonicated at room temperature to give a clear flowable composition with a lOOmg/ml concentration of drug in solution.The freshly prepared formulation was filled into ImI glass syringes via a 16 gauge blunt needle. The filling needle was then replaced with a one-half inch 21 gauge needle and lOOmul of the polymeric composition was injected subcutaneously into 12 male Wistar rats to give a total dose of lOmg of anastrozole per rat. The rats were divided into 4 sampling groups to allow blood samples from 3 animals to be collected at each of the following time intervals: baseline, 2, 4, 6, 12, 24 and 36 hours, and days 3, 4, 5, 6, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, 40, 43, and 46. Serum samples were assayed for anastrozole using a Liquid Chromatography- tandem Mass Spectrometry method (LC-MS). The serum and percentage cumulative AUC profiles, calculated from the measured anastrozole serum concentrations are shown in Figure 1. The results show that the formulation released 18% of the drug payload over the first 24 hours. Following this burst, plasma levels remained relatively constant at around 50-150ng/ml for a duration of 37 days.; Example 3: PLGA/NMP liquid formulation testing in dog; Poly(dl-lactide-co-<strong>[502-97-6]glycolide</strong>) was prepared via ring opening condensation of dl-lactide and <strong>[502-97-6]glycolide</strong> dimmers. A quantity of the polymer having a 85/15 ratio of lactide to <strong>[502-97-6]glycolide</strong>, a weight average molecular weight (MW) of 23 kDa and a terminal carboxy group was weighed into a glass sovril bottle and a sufficient amount of pre-sterile filtered N-methyl- 2-pyrrolidone (NMP) was added to give a 60:40 weight ratio of polymer to solvent. The mixture was gently stirred with the aid of a magnetic stirrer bar at room temperature until the polymer completely dissolved. The required amount of anastrozole was then added to the polymer solution and the mixture was sonicated at room temperature to give a clear flowable composition with a 100mg/ml concentration of drug in solution.The freshly prepared formulation was filled into 1ml glass syringes via a 16 gauge blunt needle. The filling needle was then replaced with a one-half inch 21 gauge needle and 300mul of the polymeric composition was injected subcutaneously into 4 male Beagle dogs to give a total of 30mg of anastrozole per dog. Serum samples were collected at EPO <DP n="20"/>baseline, 2, 4, 6, 12, 24 and 36 hours, and days 3, 4, 5, 6, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, 33, 36, 38, 40, 43, and 46.Serum samples were assayed for anastrozole using an LC-MS method. The serum and percentage cumulative AUC profiles, calculated from the measured anastrozole serum concentrations are shown in Figure 3. The results show that the formulation was capable of sustaining the release of anastrozole over a period of 30 days. Following a small drug burst over the first 24 hours (10%), plasma levels remained relatively constant at 20-40ng/ml throughout the release duration. |
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