Abstract
While the formulation of nanoparticle (NP) suspensions has been widely applied in materials and life science, the recovery of NPs from such a suspension into a solid state is practically important to confer long-term storage stability. However, solidification, while preserving the original nanoscale properties, remains a formidable challenge in the pharmaceutical and biomedical applications of NPs. Herein we combined flash nanoprecipitation (FNP) and spray-drying as a nanofabrication platform for NP formulation and recovery without compromising the dissolution kinetics of the active ingredient. Clofazimine was chosen to be the representative drug, which has been recently repurposed as a potential treatment for cryptosporidiosis. Clofazimine was encapsulated in NPs with low-cost surface coatings, hypromellose acetate succinate (HPMCAS) and lecithin, which were required by the ultimate application to global health. Spray-drying and lyophilization were utilized to produce dried powders with good long-term storage stability for application in hot and humid climatic zones. The particle morphology, yield efficiency, drug loading, and clofazimine crystallinity in the spray-dried powders were characterized. The in vitro release kinetics of spray-dried NP powders were compared to analogous dissolution profiles from standard lyophilized NP samples, crystalline clofazimine powder, and the commercially available formulation Lamprene. The spray-dried powders showed a supersaturation level of up to 60 times the equilibrium solubility and remarkably improved dissolution rates. In addition, the spray-dried powders with both surface coatings showed excellent stability during aging studies with elevated temperature and humidity, in view of the dissolution and release in vitro. Considering oral delivery for pediatric administration, the spray-dried powders show less staining effects with simulated skin than crystalline clofazimine and may be made into minitablets without additional excipients. These results highlight the potential of combining FNP and spray-drying as a feasible and versatile platform to design and rapidly recover amorphous NPs in a solid dosage form, with the advantages of satisfactory long-term storage stability, low cost, and easy scalability.
Highlights
Oral ingestion is the most convenient and commonly employed route of drug delivery because of the ease of administration, patient compliance, and flexibility in the design of the dosage form.[1]
We previously showed that NPs stabilized by zein, hypromellose acetate succinate, or lecithin enhanced the dissolution of Cfz to high levels of supersaturation following Lyo,[19] while in the current work, we aim to explore the rapid recovery of drug-loaded NPs with an appropriate SD protocol, to maintain the fast dissolution kinetics
To demonstrate a versatile nanofabrication platform that can encapsulate drug molecules into NPs and rapidly recover them from solutions without compromising the fast dissolution kinetics, the flash nanoprecipitation (FNP) process was combined with SD to produce dried NP powders
Summary
Oral ingestion is the most convenient and commonly employed route of drug delivery because of the ease of administration, patient compliance, and flexibility in the design of the dosage form.[1] Currently, up to 40% of new chemical entities discovered by the pharmaceutical industry are hydrophobic compounds in Biopharmaceutics Classification System class II, with low solubility.[2,3] The low-solubility issue leads to inadequate and variable bioavailability, requiring very high dosing or multiple-dose treatment to achieve the desired concentration in systemic circulation and, the desired pharmacological response.[4,5] a key goal in poorly soluble drug formulation is solubility enhancement, which, in turn, affords improved bioavailability and feasible dosage administration. Nanoparticle (NP) formulations can improve the bioavailability of hydrophobic drugs through two mechanisms. NPs can be formed via rapid precipitation processes to trap drug molecules in an amorphous state. The amorphous state results in a solubility of as much as 1000 times higher that of crystalline states.[6,7] Second, the greater surfaceto-volume ratio for NPs versus large drug crystals enhances the dissolution kinetics
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
