Hollow crystalline straws of diclofenac for high-dose and carrier-free dry powder inhaler formulations

• Published in: International journal of pharmaceutics Vol. 502; no. 1-2; pp. 170 - 180
• Main Authors: Yazdi, Ashkan K., Smyth, Hugh D.C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 11.04.2016
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Calorimetry, Differential Scanning; Crystallization; Diclofenac; Diclofenac - chemistry; Diclofenac sodium; Drug Delivery Systems; Dry powder inhaler; Dry Powder Inhalers; Jet milling; Microscopy, Electron, Scanning; Next generation impactor; Particle Size; Powder Diffraction; Powders; Precipitation; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; X-Ray Diffraction; ρ; DF; FT-IR; DFNa; HR; Jet milling; XRD; Diclofenac sodium (PubChem CID: 5018304); Diclofenac; HCl; FPF5μm; Precipitation; FPF3μm; Sodium dodecyl sulfate (PubChem CID: 3423265; DSC; Next generation impactor; GSD; Tween 20 (PubChem CID: 443314); FPF1μm; ED; SSA; MOC; Diclofenac (PubChem CID: 3033); Dry powder inhaler; ρB; CI; MMAD; BET; NGI; USP; ρT; RF; Diclofenac sodium; SEM; FPF; HPMC
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.02.030

[Display omitted] To crystallize diclofenac (DF) from diclofenac sodium (DFNa), to micronize DF and DFNa, and to evaluate in vitro aerodynamic performance of the jet-milled formulations From the acidic titration of aqueous DFNa, DF crystals were formed and were identified using thermal analysis, spectroscopy, and X-ray powder diffraction. Following the micronization of the DF and DFNa powders, the recovered samples were imaged, and their particle size distributions were evaluated. Samples before and after jet millings were characterized, and in vitro aerodynamic performance testing was performed on the DF sample before jet milling and the DF and DFNa samples following jet milling. Hollow needles of DF were precipitated. With similar particle size distributions, the jet-milled DFNa sample from the collection bag, and the DF sample from the cyclone were used for further characterization. Despite different deposition patterns in the Next Generation Impactor, the DF hollow needles had a comparable respirable fraction percentage to the jet-milled DF and DFNa particles. However, the jet-milled DF formulation had the best in vitro aerodynamic performance. Hollow, crystalline needles of DF were formed and possessed promising aerosol performance in comparison with the jet-milled powders.