(T1430-07-39) Modifying Drug Release from Microparticles Prepared by Spray Drying Using a 3-Fluid Nozzle

Purpose: Spray drying is a technique that converts a liquid into micron-sized powder and is commonly used in the pharmaceutical industry (1). Figure 1A shows a schematic of the spray drying process. Conventional spray drying uses a two-fluid nozzle, where the liquid feed and atomizing gas are sprayed into a heated chamber (2). The resulting powders are matrices. In contrast, a three-fluid nozzle uses two separate liquid feeds along with the atomizing gas (3). The material in the outer fluid stream may form a ‘seal’ around the inner matrix. Figure 1B shows a schematic comparing the two types of nozzles. The objective of this study was to investigate the effects of acrylic polymers with pH dependent solubility in the outer fluid stream to ‘seal’ spray dried powders prepared using a three-fluid nozzle configuration.

Methods: The water-soluble Acetaminophen (APAP) and the poorly soluble Ibuprofen (IBU) were used as model compounds. The polymers investigated included Methacrylic Acid Copolymer Type C NF (Eudragit® L 100-55) and Amino Methacrylate Copolymer NF (Eudragit® E PO). A Buchi B-290 spray dryer was used in this study. The inner fluid stream consisted of 1.6% Eudragit L and 0.8% drug. The outer fluid stream contained either 2% Eudragit L or Eudragit E.  The theoretical drug loading of the resulting powders was 18%. Polymers and drugs were dissolved in a 50:50 mixture of water and ethanol and spray dried at a rate of 2.2ml/min for each fluid stream. Inlet temperature was adjusted to achieve a drying temperature of about 55°C. Process yields, potency of the powders (expressed as the percent of theoretical drug loading) and drug release were determined. HPLC (4-5) was used to quantify drug concentration for potency and release studies.

Results: Process yields were higher for APAP formulations in comparison to IBU formulations (Figure 2A). Process yields were lower when Eudragit E was used in the outer fluid stream in comparison to Eudragit L formulations (Figure 2A). This was especially apparent in the IBU formulation, suggesting a possible interaction between the basic polymer and acidic drug. Potencies were > 90%, irrespective of the drug or polymer (Figure 2B). Release of IBU was significantly decreased in pH 2 when Eudragit L was used in the outer stream in comparison to pH 6.8, suggesting that the powders were ‘sealed’. In contrast, the release of APAP in pH 2 was not significantly different than in pH 6.8 when Eudragit L was used (Figure 3A). However, drug release of APAP in pH 6.8 was decreased when Eudragit E was in the outer fluid stream (Figure 3B) in comparison to release at pH 2, which shows promise for taste masking applications. Yields were so low with the Eudragit E/IBU formulation that drug release studies were not conducted.

Conclusion: Overall, these results suggest that spray drying using the three-way nozzle with polymers that exhibit pH-dependent solubility can be used to modify drug release. Ongoing research is investigating a number of variables, including drug and polymer concentrations as well as different polymers in the inner fluid stream.

References: 1. Ҫelik, et al, Spray Drying and Pharmaceutical Applications, from Handbook of Pharmaceutical Granulation Technology, 4th ed., CRC Press, 2021.
2. Price, Stromberg, Kunda, and Muttil, Molecul Pharm, 2017.
3. Kondo, Niwa, and Danjo, Eur J Pharm Sci, 2014.
4. Felton et al, AAPS PharmSciTech, 2014.
5. Macchi et al, Eur J PharmSci, 2016.

Acknowledgments: This work was supported in part by an NIH grant (R21HD095100). We would like to thank Evonik for donating the polymers used in this study.

Figure 1. Schematic of the spray drying process (A) and the two nozzles configurations (B).



Figure 2. Comparison of the process yields (A) and the potency (B) as a function of drug and polymer in the outer fluid stream.



Figure 3. Drug release at 5 minutes in pH 2 or 6.8 as a function of polymer in the outer fluid stream (A) Eudragit L; (B) Eudragit E.