An Improved 2-Step Process for Moisture Sensitive Drugs Using Syloid® FP Silicas

Introduction: Several APIs are sensitive to moisture, and formulating these drugs into stable oral dosage forms can pose quite a challenge to formulators. There are several potential problems associated with moisture sensitive drugs, such as caking and poor flow properties, chemical degradation, changes in dissolution rates, and decrease in shelf life of the drug. Before considering special packaging to protect moisture sensitive formulations, one should first consider selecting the right excipients and formulation techniques to help stabilize moisture sensitive APIs. Porous silica gel, such as Syloid® FP silicas, can help improve the stability of moisture sensitive APIs by adsorbing moisture in the final formulation.

Direct compression is another technique that is recommended for moisture sensitive APIs, as it does not involve heat, moisture, and long blending times, unlike other techniques such as wet and dry granulation methods. Therefore, using porous silicas in direct compression formulations can potentially provide the maximum benefits to moisture sensitive drugs. Porous silica gel, such as Syloid® 244FP silica, is typically used in formulations as a glidant in small amounts (up to 2%). For adequate moisture protection, such low quantities would not be sufficient. Another grade of porous silica, Syloid® AL-1FP/63FP silica, is particularly effective for providing moisture protection, and can be incorporated into formulations in larger amounts, depending on the % CRH as well as nature and amount of API in the formulation.

Here, we demonstrate that addition of the two different grades of porous silicas (Syloid® AL-1FP/63FP and Syloid® 244FP silica) through a two-step mixing process can provide the combined benefits of moisture protection and flow improvement to a formulation. We also demonstrate that greater quantities of porous silica (5-20%) required to provide moisture protection can be used, while maintaining compressibility of the formulation mixture.

Hygroscopic products, such as plant related API’s, antiinfectives, lyophilized products, probiotica, and many others can adsorb moisture from the air and adhere together. Caking can also occur when powders are not completely dry or when moisture migrates towards the outer surface after drying in wet granulation. The high porosity of Syloid® FP silica can adsorb a considerable amount of moisture, keeping the product dry and improving the stability.

Ascorbic acid was used as a model drug in a direct compression formulation to demonstrate the effects of different amounts of silica on flow and tablet parameters. We evaluated the effect of different amounts of Syloid® AL1FP/63FP silica on the flow behavior and the compressibility of the final formulation, with both 10% and 40% drug loading. Syloid® 244 FP silica is used at 1% in all the formulations to provide optimum glidant benefits. The amount of Syloid® AL1FP/63FP silica was varied from 5-20% of the formulation.

We first tested the flow parameters of the final mixture with and without Syloid® AL-1FP/63FP silica at different percentages. The mixtures were then compressed into tablets by direct compression. The resulting tablets were evaluated for such as hardness, friability, weight uniformity, etc. The tablets maintained favorable properties with respect to weight uniformity, hardness, friability and disintegration, with both 10% and 40% API loading. The tablet hardness was between 6kg/cm2 and 12.50kg/cm2 with 5-20% Syloid® AL-1FP/63FP silica and weight uniformity (RSD) is not more than 0.82% for 10% API loading. The tablet hardness is less with 20% Syloid® AL-1FP/63FP silica at 40% API loading. However, the tablet hardness can be improved by increasing compression force during tabletting.

Conclusions: We successfully demonstrate that tablets can be prepared by direct compression method using Syloid® AL-1FP/63FP silica from 5-20% at different API loading 10% and 40%. We found that the tablet properties are very good with 10% API loading at all percentages of Syloid® AL-1FP/63FP silica from 5-20%. For 40% API loading, the tablet properties are good with up to 15% Syloid® AL-1FP/63FP silica. The tablet parameters such as hardness, friability and weight uniformity were found to depend on both percentage of API (10% or 40%) and percentage of Syloid® AL-1FP/63FP silica (5-20%) in the tablets. We are also investigating the effects of larger amounts of silica on other parameters such as disintegration times and dissolution rates. By optimizing these factors in a formulation for different drugs, sufficient amounts of porous silicas can be incorporated into direct compression formulations, to provide optimal moisture protection to the formulation.

 Download the full article as a PDF here