Designing a package for pharmaceutical tablets in relation to moisture and dissolution

Dissolution can be used as a measure of bioavailability and as a stability-indicating parameter for pharmaceutical tablets. Therefore, it is very important to predict the dissolution of pharmaceutical tablets in a package in order to design a package for stability testing. In order to predict the dissolution, the relationship between dissolution, storage time and relative humidity must be determined. So, tablets were stored in open dishes at two different temperatures (25 and 40°C) and five different relative humidities (0, 50, 65, 75, 90% RH) for 6 months.; Dissolution was measured every month for 6 months, and the dissolution was plotted with storage time to determine a dissolution retardation rate (R, dissolution change/day). At each relative humidity, tablets have a specific dissolution retardation rate. Therefore, dissolution retardation rates can be plotted as a function of relative humidity to determine the relationship between dissolution retardation rate and relative humidity. Based on that relationship, a dissolution prediction model can be developed. From the dissolution prediction model, dissolution can be calculated at any relative humidity for a given amount of storage time. The relative humidity of the package headspace changes in the unsteady state, so the dissolution of tablets stored at any condition is very hard to estimate. However, computer programs make it possible.; A Windows based dissolution prediction program was developed in this study. The dissolution prediction program can calculate the dissolution change of tablets in a package as a function of storage time. In order to calculate the dissolution change, a proprietary moisture prediction program was also developed in the dissolution prediction program. The moisture prediction program can calculate the moisture content of solids in a package and RH of the package headspace.{09}The program can be used to save time and money in a variety of applications such as determining the amount of desiccant and package barrier requirement for a given shelf life.; The moisture and dissolution prediction programs were verified by using experimental results. Uncoated drug tablets and silica gel were inserted into LDPE bags and HDPE bottles. The moisture content of the tablets and silica gel was measured as a function of storage time, and then this was compared to the results from the moisture prediction program. The differences between predicted and experimental moisture contents ranged from 0% to 0.39% for tablets and 0.11 to 6.50% for silica gel. Also, dissolution results from the dissolution prediction program were compared with the experimental results to verify the program. The differences between predicted and experimental dissolution ranged from 1.3 to 13.5% for LDPE bags and 0 to 18.3% for HDPE bottles. The differences are fairly large because tablets behave in a variety of manners. In this study, a new theory of the relationship between dissolution retardation and relative humidity is proposed.; The open dish study and computer simulation programs are useful in providing an effective way to select an appropriate package for registration stability testing.