Can APIs that are Poorly Water‐ and Oil‐Soluble Benefit from Incorporation into SMEDDS? The Case of Dipyridamole

Abstract

AbstractThe aim of this study is to develop a self‐microemulsifying drug delivery system (SMEDDS) for the model active pharmaceutical ingredient (API) dipyridamole using exclusively excipients suitable for oral administration and nonvolatile cosolvents. Dipyridamole is a poorly water‐soluble and poorly oil‐soluble compound, which made it an atypical candidate for development of a lipid‐based drug delivery system (LBDDS). Four SMEDDS are successfully formulated, and dipyridamole has up to 1750‐fold higher solubility in the SMEDDS compared to water. Incorporation of 0.6–1% of dipyridamole into the SMEDDS does not considerably affect the droplet size, uniformity of droplet size distribution, and self‐emulsifying properties of the SMEDDS. The applicability of hard capsules for developing a final solid dosage form is tested by dissolution studies of dipyridamole from SMEDDS filled in gelatin and hydroxypropyl methylcellulose (HPMC) hard capsules. In addition, empty SMEDDS are filled into gelatin and HPMC hard capsules. They are stored for 16 weeks at ambient conditions and at 40 °C and 75% relative humidity. The dissolution properties and solubility of dipyridamole are considerably enhanced by incorporating dipyridamole into the SMEDDS; however, development of a final dosage form with hard capsules that are leak‐free for an extended period and at higher temperatures/humidity is still pending.Practical Applications: This study suggests that substances with low water solubility and low oil solubility can also benefit from incorporation into SMEDDS. Excipient selection needs to be considered carefully for such cases to maximize API incorporation and to ensure the self‐emulsifying properties of the formulation. In addition, only nonvolatile and orally acceptable excipients are used for preparation of SMEDDS, which is important when developing a formulation aimed for oral application. Hard capsules are a common approach for preparation of final dosage forms; however, obtaining leak‐free capsules can be challenging when liquid SMEDDS are used as filling. Storage for prolonged period and at higher temperatures/humidity is necessary for evaluation of liquid SMEDDS‐filled hard capsules.