For inhalation drug delivery, amorphous powder formulations offer the benefits of increased bioavailability for poorly soluble drugs, improved biochemical stability for biologics, and expanded ...options of using various drugs and their combinations. However, amorphous formulations usually have poor physicochemical stability. This review focuses on inhalable amorphous powders, including the production methods, the active pharmaceutical ingredients and the excipients with a highlight on stabilization of the particles.
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The efficacy of pharmaceutical aerosols relates to its deposition in the clinically relevant regions of the lungs, which can be assessed by in vivo lung deposition studies. Dry powder formulations ...are popular as devices are portable and aerosolisation does not require a propellant. Over the years, key advancements in dry powder formulation, device design and our understanding on the mechanics of inhaled pharmaceutical aerosol have opened up new opportunities in treatment of diseases through pulmonary drug delivery. This review covers these advancements and future directions for inhaled dry powder aerosols.
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Novel inhaled therapeutics including antibiotics, vaccines and anti-hypertensives, have led to innovations in designing suitable delivery systems. These emerging design technologies are in urgent ...demand to ensure high aerosolisation performance, consistent efficacy and satisfactory patient adherence. Recent vibrating-mesh and software technologies have resulted in nebulisers that have remarkably accurate dosing and portability. Alternatively, dry powder inhalers (DPIs) have become highly favourable for delivering high-dose and single-dose drugs with the aid of advanced particle engineering. In contrast, innovations are needed to overcome the technical constrains in drug–propellant incompatibility and delivering high-dose drugs with pressurised metered dose inhalers (pMDIs). This review discusses recent and emerging trends in pulmonary drug delivery systems.
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In vitro-in vivo correlation is the establishment of a predictive relationship between in vitro and in vivo data. In the context of cascade impactor results of orally inhaled ...pharmaceutical aerosols, this involves the linking of parameters such as the emitted dose, fine particle dose, fine particle fraction, and mass median aerodynamic diameter to in vivo lung deposition from scintigraphy data. If the dissolution and absorption processes after deposition are adequately understood, the correlation may be extended to the pharmacokinetics and pharmacodynamics of the delivered drugs. Correlation of impactor data to lung deposition is a relatively new research area that has been gaining recent interest. Although few in number, experiments and meta-analyses have been conducted to examine such correlations. An artificial neural network approach has also been employed to analyse the complex relationships between multiple factors and responses. However, much research is needed to generate more data to obtain robust correlations. These predictive models will be useful in improving the efficiency in product development by reducing the need of expensive and lengthy clinical trials.
Nanodrugs: pharmacokinetics and safety Onoue, Satomi; Yamada, Shizuo; Chan, Hak-Kim
International journal of nanomedicine,
01/2014, Letnik:
9, Številka:
Issue 1
Journal Article
Recenzirano
Odprti dostop
To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and ...polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges.
Drug dosing in critically ill patients is challenging due to the altered drug pharmacokinetics-pharmacodynamics associated with systemic therapies. For many drug therapies, there is potential to use ...the respiratory system as an alternative route for drug delivery. Aerosol drug delivery can provide many advantages over conventional therapy. Given that respiratory diseases are the commonest causes of critical illness, use of aerosol therapy to provide high local drug concentrations with minimal systemic side effects makes this route an attractive option. To date, limited evidence has restricted its wider application. The efficacy of aerosol drug therapy depends on drug-related factors (particle size, molecular weight), device factors, patient-related factors (airway anatomy, inhalation patterns) and mechanical ventilation-related factors (humidification, airway). This review identifies the relevant factors which require attention for optimization of aerosol drug delivery that can achieve better drug concentrations at the target sites and potentially improve clinical outcomes.
Dry powder inhalers (DPIs) can be used with a wide range of drugs such as small molecules and biologics and offer several advantages for inhaled therapy. Early DPI products were intended to treat ...asthma and lung chronic inflammatory disease by administering low-dose, high-potency drugs blended with lactose carrier particles. The use of lactose blends is still the most common approach to aid powder flowability and dose metering in DPI products. However, this conventional approach may not meet the high demand for formulation physical stability, aerosolisation performance, and bioavailability. To overcome these issues, innovative techniques coupled with modification of the traditional methods have been explored to engineer particles for enhanced drug delivery. Different particle engineering techniques have been utilised depending on the types of the active pharmaceutical ingredient (e.g., small molecules, peptides, proteins, cells) and the inhaled dose. This review discusses the challenges of formulating DPI formulations of low-dose and high-dose small molecule drugs, and biologics, followed by recent and emerging particle engineering strategies utilised in developing the right inhalable powder formulations for enhanced drug delivery.
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