Issue link: http://www.e-digitaleditions.com/i/552614
The fundamentals-based "science first" approach has proven itself to be flexible across API types, from small molecules to nucleic acids and protein therapeutics, and across a range of drug loadings. The albuterol case study highlights the potential of spray dry manufacture to create a defined inhalation-grade, high performing particle with a minimal amount of time or budget invested. Considerations inherent to an optimized formulation strategy based on spray dry technology process, and which heavily impact design and performance include: 1. Compound physical characteristics such as melt tem- perature and aqueous/organic solubilities 2. The rationale and need for excipients in a final dosage form, as well as their physical characteristics 3. A manufacturing strategy that includes target critical quality attributes at every step of drug product develop- ment 4. Capsule type and design that meet desired powder retention and aerosol characteristics 5. Device type selection that supports analytical, aerosol performance, therapeutic target and patient population. As exhibited in the albuterol case study, critical compo- nents for an amorphous formulation based on spray dry technology can be successfully developed for inhaled med- ications: a robust formulation, a manufacturing process with minimized complexity and capsule-based delivery system. Spray dry dispersion technology has established market precedence and has been further optimized for a wide range of formulation and particle design concepts for inhalation and intranasal drug delivery. Capsugel Dosage Form Solutions/Bend Research has integrated these com- ponents into a streamlined and de-risked drug develop- ment approach with resultant expedited proof of concept and clinical study test material for a wide range of active pharmaceutical ingredients and dose ranges. References 1. David Prime, Paul J. Atkins, Anna Slater, Barry Sumby, "Review of Dry Powder Inhalers," Advanced Drug Delivery Reviews 26, no. 1 (1997): 51-58. 2. Allen Feng, Mohammed Boraey, Morgan Gwin, P.R. Finlay, Philip Kuehl, Reinhard Vehring, "Mechanistic Models Facilitate Efficient Development of Leucine Containing Microparticles for Pulmonary Drug Delivery," International Journal of Pharmaceutics 409, nos. 1-2 (2011): 156-163. 3. Mohammed A. Boraey, Susan Hoe, Hajar Sharif, Danforth P. Miller, David Lechuga-Ballesteros, Reinhard Vehring, "Improve- ment of the Dispersibility of Spray-Dried Budesonide Powders Using Leucine in an Ethanol–Water Cosolvent System," Powder Technol- ogy 236 (2013): 171-178. 4. M. Sherry Ku, Weiyi Li, Wendy Dulin, Fran Donahue, Dominique Cade, Hassan Benameur, Keith Hutchison, "Perfor- mance Qualification of a New Hypromellose Capsule: Part I. Com- parative Evaluation of Physical, Mechanical and Processability Qual- 12 AUGUST 2015 Inhalation Figure 3 30% 25% 20% 15% 10% 5% 0% Capsule Device Throat Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Stage 6 Stage 7 Stage 8 MASS% 10%A BLD-35 10%A PSD-1 40%A BLD-35 40%A PSD-1 Impaction study results of spray dried albuterol powders. API loading and manufacturing scale were varied in this study. (MOC) (USP)