China
Africa
Explore chapters and articles related to this topic
Particle Engineering Technology for Inhaled Therapies
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
David Lechuga-Ballesteros, Susan Hoe, Benjamin W. Maynor
Commonly used excipients to form stable organic glasses are lactose, sucrose, raffinose, trehalose, and sodium citrate. Glass stabilization technology was successfully used to engineer spray dried inhalable insulin (Exubera® by Pfizer) using citrate, mannitol, and glycine, providing a superior long-term stability compared to insulin in solution (Sadrzadeh et al. 2010). Glycine acts as a buffer for the protein during manufacturing, mannitol is used as the plasticizer, and sodium citrate both provides the ionic strength required to dissolve insulin in the spray dryer feedstock and acts as a glass former (high glass transition). In addition to its superior solid-state stability, spray dried insulin powders displayed excellent aerosol properties in both dry and wet environments. Spray dried amorphous sugars tend to render cohesive powders with poor aerosol performance. However, in the case of Exubera®, insulin is surface active and possesses a high glass transition; as a result, during particle formation, it enriches the droplet surface and dominates the particle surface properties, negating the need for additional excipients to decrease cohesion. This is not always the case, as some peptides, such as spray dried salmon calcitonin, present poor aerosol performance and addition of excipients to modify surface properties to decrease cohesion is often needed (Chan et al. 2004).
Physicochemical properties of respiratory particles and formulations
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Porous particles or hollow particles can be obtained by a variety of different processing techniques, including spray drying, spray freezing, emulsion and some supercritical fluid (SCF) methods (see Table 1.2 and Figure 1.5). From the currently marketed formulations, one needs to mention fast-acting inhalable insulin drug product (Afrezza®) which is composed of aggregates (2–3 μm) of fumaryl diketopiperazine (FDKP) nanosize platelet crystals, providing a high SSA with insulin absorbed on or otherwise distributed within these aggregates. The bioavailability of insulin is significantly enhanced with FDKP, also leading to a fast onset of action for this formulation. This method can be classified in a group where carriers are produced by crystallization or coacervation in liquid solutions (15).
An expert opinion on respiratory delivery of high dose powders for lung infections
Published in Expert Opinion on Drug Delivery, 2022
Bishal Raj Adhikari, Jack Dummer, Keith C. Gordon, Shyamal C. Das
RDD with high dose powder also holds potential to treat infections or diseases in other parts of the body by achieving the desired blood concentration being alternate or adjunct to oral or intravenous therapy. For example, tuberculosis meningitis for which rifampicin was found to achieve only suboptimal blood and cerebrospinal fluid (CSF) concentration, when the maximum allowable dose (20 mg/kg) or 600 mg was given orally, and therefore, a higher dose of rifampicin was recommended [142]. However, Khadka et al. have shown that bioavailability of rifampicin via inhalation route was higher than via oral route in an animal model, and inhaled rifampicin combined with oral dose could ensure higher concentration of the drug in the lung and blood than similar oral dose alone [143]. In comparison to intravenous route, dry powder inhalers empower patients with the possibility of needleless, self-administration which could improve adherence. Therefore, high dose inhaled delivery is a potential approach to treat infections in the brain to overcome suboptimal level of drugs offered by current oral doses. Similarly, reformulating other drugs for systemic delivery through the lungs should also be a continued research interest. An inhalable insulin, Exubera®, was approved for diabetes in 2006 [144]. Although this product was later withdrawn likely due to commercial non-viability and safety concerns, other inhalable insulin products (e.g. Afrezza®) have made it to the market [140]. Other molecules which are being investigated for delivery through lungs for systemic effects include prochlorperazine for migraine (phase II completed) [145] and apomorphine for Parkinson disease (phase II completed) [146].
Preparation, characterization, and pharmacodynamics of insulin-loaded fumaryl diketopiperazine microparticle dry powder inhalation
Published in Drug Delivery, 2019
Yun Xia, Yipeng Su, Qiyue Wang, Chen Yang, Baoqiang Tang, Yue Zhang, Jiasheng Tu, Yan Shen
Towards this end, [Bis-3,6(4-fumarylaminobutyl)-2,5-diketopiperazine] (FDKP) is an FDA approved inert excipient that has been used as the primary component in Afrezza® to assist in the delivery of recombinant human insulin via inhalation (Rendell, 2014; Maker et al., 2017). As a new excipient, FDKP is chemically inert and can be assembled into microspheres by hydrogen bonding under acidic conditions and dissolves under neutral and alkaline conditions (Angelo et al., 2009). The microspheres could adsorb the insulin through electrostatic interactions to form microparticles in a range between 0.5 and 10μm, more specifically 3–5μm (geometric particle size and MMAD) for insulin particles (Liu et al., 2008). Absorbed FDKP is directly excreted from the kidneys without metabolism which avoiding the toxicity of degradation products. Although the inhaled insulin powder Afrezza®, which has been marketed, can significantly reduce the incidence of hypoglycemia and relieve the pain of patients, the sales volume and the market feedback of Afrezza® is unsatisfactory as well. The reason for the poor sales of Afrezza® may be that people are still skeptical about the safety of insulin DPIs, and the price of the inhaler and its associated inhalation device is higher than that of insulin injection (Fantasia, 2015). Compared with Afrezza®, this paper aims to optimize the preparation process of INS@FDKP-MPs by adopting a simpler and more convenient synthesis method to reduce the production cost, and by evaluating the properties of INS@FDKP-MPs, it is intended to construct an inhalable insulin preparation that is qualified in particle size, drug loading, hypoglycemic effect, and safety.