(645f) Melt-Coating of APIs with Surfactant for Drug Dissolution Enhancement

For a solid dosage form, medicine is dispensed based on the dissolving of the active ingredient in the gastrointestinal tract. The significance of the dissolution rate on drug clinical performance has been recognized for a long time. One of the most critical quality attributes was assessed depends on its dissolution behavior. Unfortunately, significant numbers of FDA approved drugs and developmental drugs are hydrophobic and poorly soluble. It has been documented that approximately 40% of approved drugs and 90% of drugs under development are categorized as molecules of low water-solubility and low bioavailability. Due to discovering new drugs is increasing difficulty and become a non-effective way to approach therapeutic requirements, enhancing the solubility of these available drugs is considerably investigated. The prevalent approach for dissolution improvement can be ionizing the drug molecules, producing salt from, micronizing API particles, and using solid dispersion techniques. However, these techniques may require complex unit operations, create unstable solid forms, or generate APIs of poor manufacturability. In this work, we will propose a novel approach in which a small amount of surfactant (< 10% of API weight) is coated on the surface of API particles by applying shearing and heat simultaneously. In this way, we are able to enhance the dissolution of hydrophobic and insoluble API without changing its original solid state.

In our work, three poorly soluble APIs (Ibuprofen, Carbamazepine, and Fenofibrate) and two low-melting-point surfactants (Poloxamer407 and Cetylpyridinium Chloride) are selected. Three specific case studies are performed. In each case study, a twin-screw extruder is used to perform melt-coating because it can apply shearing and heat simultaneously. At a certain temperature, the surfactant can partially melt, then smears and coats on the surface of API particles. Then, the hydrophobic APIs presents a new hydrophilic surface. The particle morphology is photographed using SEM, which shows that the surfactant successfully coats on API particles.

Then, the dissolution test is performed for both treated powder and finished product (tablet and capsule) and compared with the physical mixture and no-surfactant case. Results show that the melt-coating of the surfactant considerably enhances the dissolution rate. The treated product can release drugs 2-5 times faster than the physically mixed product. In contrast, the physical blending surfactant has a marginal effect on dissolution in comparison to the no-surfactant case.