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Advanced Drug Delivery Reviews (v.64, #3)
Lactose as a carrier for inhalation products: breathing new life into an old carrier
by Chris Marriott Theme Editor; Henderik W. Frijlink Theme Editor (pp. 217-219).
Physico-chemical aspects of lactose for inhalation by Xiang Kou; Lai Wah Chan; Hartwig Steckel; Paul W.S. Heng (pp. 220-232).
A dry powder inhaler (DPI) is a dosage form that consists of a powder formulation in a device which is designed to deliver an active ingredient to the respiratory tract. It has been extensively investigated over the past years and several aspects relating to device and particulate delivery mechanisms have been the focal points for debate. DPI formulations may or may not contain carrier particles but whenever a carrier is included in a commercial formulation, it is almost invariably lactose monohydrate. Many physicochemical properties of the lactose carrier particles have been reported to affect the efficiency of a DPI. A number of preparation methods have been developed which have been claimed to produce lactose carriers with characteristics which lead to improved deposition. Alongside these developments, a number of characterization methods have been developed which have been reported to be useful in the measurement of key properties of the particulate ingredients.This review describes the various physicochemical characteristics of lactose, methods of manufacturing lactose particulates and their characterization.Display Omitted
Keywords: Dry powder inhaler; Physicochemical properties; Manufacture; Characterization; Lactose
Lactose characteristics and the generation of the aerosol by Gabrielle Pilcer; Nathalie Wauthoz; Karim Amighi (pp. 233-256).
The delivery efficiency of dry-powder products for inhalation is dependent upon the drug formulation, the inhaler device, and the inhalation technique. Dry powder formulations are generally produced by mixing the micronised drug particles with larger carrier particles. These carrier particles are commonly lactose. The aerosol performance of a powder is highly dependent on the lactose characteristics, such as particle size distribution and shape and surface properties. Because lactose is the main component in these formulations, its selection is a crucial determinant of drug deposition into the lung, as interparticle forces may be affected by the carrier-particle properties. Therefore, the purpose of this article is to review the various grades of lactose, their production, and the methods of their characterisation. The origin of their adhesive and cohesive forces and their influence on aerosol generation are described, and the impact of the physicochemical properties of lactose on carrier-drug dispersion is discussed in detail.Display Omitted
Keywords: Abbreviations; AFM; Atomic Force Microscopy; CI; compressibility index; D(0.5); mass median diameter; D; ae; aerodynamic diameter; DPI; dry-powder inhaler; DPPC; dipalmitoylphosphatidylcholine; DSC; differential scanning calorimetry; DVS; dynamic vapour sorption; ED; emitted dose; ELPI™; electrical low-pressure impactor; FPD; fine particle dose; FPF; fine particle fraction; HPMC; hydroxypropyl methyl cellulose; HR; Hausner ratio; IGC; inverse gas chromatography; LOQ; limit of quantification; MMAD; mass median aerodynamic diameter; Mg st; magnesium stearate; PSD; particle size distribution; RH; Relative humidity; RSD; relative standard deviation; SCF; supercritical fluid; SEM; scanning electron microscopy; XRPD; X-ray powder diffractionDry powder inhaler; Carrier; Particle interaction; Surface properties; Characterisation; Inhalation
A critical view on lactose-based drug formulation and device studies for dry powder inhalation: Which are relevant and what interactions to expect? by A.H. de Boer; H.K. Chan; R. Price (pp. 257-274).
Many years of research have not led to a profound knowledge of the mechanisms involved in the formulation and dispersion of carrier based mixtures for inhalation. Although it is well understood that the mixing is a key process in DPI carrier based formulation, there remains a limited understanding of how blending processes affect in-process material properties and the resulting distribution of the drug in the final dosage form. A great number of variables are considered relevant to the interfacial forces in adhesive mixtures, but their effects have mostly been investigated individually, without taking account of the influence they may have on each other. Interactions may be expected and without proper choices made and definitions given for all the variables involved, conclusions from studies on adhesive mixtures are of less relevance. By varying any of the variables that are not subject of the study, an opposite effect may be obtained. Currently, there is a strong focus on exploring techniques for the characterisation of drug and carrier surface properties that are believed to have an influence on the interparticulate forces in adhesive mixtures. For a number of surface properties it may be questioned whether they are really the key parameters to investigate however. Their orders of magnitude are subordinate to the effects they are supposed to have on the drug-to-carrier forces. Therefore, they seem rather indicators of other variability and their influence may be dominated by other effects. Finally, the relevance of inhaler design is often ignored. By using powerful inhalers, the effect of many variables of current concern may become less relevant. Carrier properties that are considered disadvantageous at present may even become desirable when a more appropriate type of dispersion force is applied. This can be shown for the effect of carrier surface rugosity when inertial separation forces are applied instead of the more widely applied lift and drag forces. Therefore, inhaler design should be taken into consideration when evaluating studies on adhesive mixtures. It should also become an integral part of powder formulation for inhalation.Display Omitted
Keywords: Adhesive mixtures; Carrier lactose; Drug formulation; Pulmonary drug deposition; Powder mixing; Dispersion; Inhaler development
Drug–lactose binding aspects in adhesive mixtures: Controlling performance in dry powder inhaler formulations by altering lactose carrier surfaces by Qi (Tony) Zhou; David A.V. Morton (pp. 275-284).
For dry powder inhaler formulations, micronized drug powders are commonly mixed with coarse lactose carriers to facilitate powder handling during the manufacturing and powder aerosol delivery during patient use. The performance of such dry powder inhaler formulations strongly depends on the balance of cohesive and adhesive forces experienced by the drug particles under stresses induced in the flow environment during aerosolization. Surface modification with appropriate additives has been proposed as a practical and efficient way to alter the inter-particulate forces, thus potentially controlling the formulation performance, and this strategy has been employed in a number of different ways with varying degrees of success. This paper reviews the main strategies and methodologies published on surface coating of lactose carriers, and considers their effectiveness and impact on the performance of dry powder inhaler formulations.Display Omitted
Keywords: Dry powder inhaler; Lactose carrier; Adhesive mixture; Aerosol performance; Force control agents; Cohesive–adhesive balance; Surface modification; Mechanical dry powder coating; Surface coating characterization
The use of inverse gas chromatography for the study of lactose and pharmaceutical materials used in dry powder inhalers by Matthew D. Jones; Paul Young; Daniela Traini (pp. 285-293).
Inverse gas chromatography (IGC) is a sensitive technique for the measurement of powder surface properties, especially surface energetics. Given the importance of these characteristics to the performance of dry powder inhaler formulations (DPIs), it is unsurprising that IGC has been applied to the study of these systems. Monitoring batch-to-batch variation and the effects of processing steps are established uses of IGC in this field and the relevant studies are discussed. A less established use of IGC is for the prediction of DPI performance. Although some groups have found a negative relationship between the dispersive surface energy of one formulation component and fine particle delivery, such studies often have a number of limitations. More complex approaches have failed to produce consistent results. Further, more carefully designed, studies are required in this area. In the final section of this article, some areas for on-going research are discussed, including the need to critically assess the best method for the calculation of the specific free energy of adsorption with pharmaceutical materials.
Keywords: Batch-to-batch variation; Blending; Dry powder inhalers; Inverse gas chromatography; Milling; Surface energy; Fine particle fraction; Free energy of adsorption; Surface properties