현탁제 제조공정에서 발생된 거품이 완제품 주성분 함량에 미치는 영향

Influence of Foam generated in Pharmaceutical Suspensions Manufacturing Process on Active Pharmaceutical Ingredient Contents of Finished Products

This study aimed to investigate the influence of foam generated in the pharmaceutical suspension manufacturing process on finished products’ active pharmaceutical ingredient (API) contents. In particular, we aimed to evaluate the possibility of having a higher API content in pharmaceutical suspensions containing a large amount of foam. We also investigated content analysis results based on prior studies related to the attachment of solid particles to bubbles. Each test tube was agitated at 1,200 rpm for 60 min to generate bubbles. To measure the API content, samples were collected from each layer (lower, middle, upper, foam). The API content analysis results were further analyzed by general properties (pH and density), surface hydrophobicity (contact angle), and morphological properties (particle size and shape). The API content in five out of seven pharmaceutical suspensions increased toward the upper layer, and the API concentration of the foam layer was the highest. The other two suspensions showed an opposite trend. The contact angle of API particles of products with an increased toward the upper layer was greater than 62o, the particle size exceeded 4μm, and the particles were needle-shaped and had angular fragments. Our findings indicate that API particles are highly concentrated in the foam generated during the manufacturing process depending on various properties, including surface hydrophobicity, particle size, and shape. Therefore, improvements in formulations and the manufacturing process of pharmaceutical suspensions such as foam suppression or breakage rather than foam removal from the intermediate products are required.