| Summary: | 碩士 === 國立臺灣大學 === 藥學研究所 === 89 === Abstract
Generally, the dosage forms by pharmaceutical companies only meet the needs of majority, but not to some of the minority, such as children and elderly. Therefore practicing pharmacists must apply their compounding skill and knowledge to fill in this gap to fulfill individualized needs. Providing compounding service for divided powders for pediatric patients has been considered as a required service in most of the health care institutions in Taiwan. However, without adequate quality control, the quality of compounding divided powders from tablets is questionable. From a pilot study on the quality of compounded powder packets in National Taiwan University Hospital (NTUH), it was revealed that the weight variation and content uniformity of those packets did not meet the regulation requirements in Pharmacopoeia to most of drugs. The average content of drug was commonly lower than the labeled content. To ensure the quality of compounding drugs, establishing standard operation procedures (SOP) is necessary especially for institutions whose compounding operating in a pre-packed batch size manner, such as NTUH. Besides, it is also important to have the stability data to determine the 「beyond-use date」 for a drug after compounding.
Captopril, propranolol HCl, and warfarin Na, which have been often prescribed in divided doses or which have narrow therapeutic range, were chosen as the model drugs to study the factors, such as batch size, diluent amount added, and content specification of powder packets, that may influence the compounding quality for divided powders. Also, the stability of divided powders of these three drugs was another concern.
A 23 factorial design was applied to study the factors that affect the quality of compounding of drug powder. Therefore, there were eight compounding combinations for each drug. The monitor items of quality included the coefficient of variation of powder weight, the coefficient of variation of drug content, the coefficient of variation of content per unit weight, and the percentage of labeled content. The data were collected and analyzed by regression analysis. The a priory level of significance was set at < 0.05.
The results of quality assurance study indicated that reducing the batch size of each compounding operation improved the uniformity of powder weight and drug content, while increasing amount of diluent added increased the average content of powder packets to an extent of about 10%. If we applied the criteria of content uniformity listed in pharmacopoeia to check the results of the eight combinations of these three drugs. There was only one combination of propranolol HCl that totally meet the criteria. We also found that the actual drug content of each package of different content specifications overlap to each other. It was also clear to see that the official allowed content range (85-115%) of different content specifications, whose contents are very close to each other overlap to each other. Consequently, a lot of divided powders of very closed content specifications list in formulary turned out to be not significant clinically.
To study drug stability after compounding, a total of 60 powder packets of each drug were prepared and stored at 25℃ and protect from light in two desicators of 18% RH and 80% RH, respectively. Samples were withdrawn and analyzed for drug content and powder weight at the time immediately after preparation and at 28, 56, and 84 days of storage. The data in two different humidity conditions and at different storage times were compared by Student’s t test for unpaired data.
The results of stability test indicated that because the stability profiles of the three drugs were different and the water proofing property of glassine papers used was not quite good. It was shown that captopril in powder packets under 18% RH was stable for 28 days only; warfarin Na was stable for 84 days in both 18 % RH and 80 % RH conditions; propranolol HCl was stable for 84 days in 18% RH condition. Overall, all the powder packets should be stored at a controlled low humidity condition. It is suggested that the beyond-use date of other drugs after compounding should be reevaluated with some stability data to ensure the quality of compounded drugs provided to patients.
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