Spray drying: Inhalable powders for pulmonary gene therapy.

Gene therapy holds potential in the treatment of many lung pathologies, as indicated by the growing number of clinical trials in recent decades. Pulmonary delivery of gene therapies via inhalation enables localised treatment while the extensive lung surface area promotes enhanced drug absorption. However, loss of nucleic acid integrity during the aerosolisation process, pulmonary clearance, and undesirable drug deposition, pose a major challenge for local delivery. Therefore, the development of nucleic acids into a stable inhalable pharmaceutical preparation would be advantageous. Dry powder inhalers (DPIs) are considered superior compared to nebulisation and pressurised-metered dose inhalers (pMDIs) due to the production of a stable dry formulation, an easy dispensing process, and minimal physical stress. DPIs are commonly produced via spray drying with a range of excipients, solvents, and separation options which can be modified to improve the stability of the nucleic acid cargo. This review details the ideal characteristics for pulmonary delivery and formulation of DPIs for gene therapy to the lungs. The utilisation of spray drying for the production of nucleic acid-containing DPIs is evaluated, with a specific focus on the influence of instrument parameters, the nucleic acid delivery system, and excipients with respect to cargo stability and functionality.

The effect of polymer coatings on physicochemical properties of spray-dried liposomes for nasal delivery of BSA.

This work describes the development of spray dried polymer coated liposomes composed of soy phosphatidylcholine (SPC) and phospholipid dimyristoyl phosphatidylglycerol (DMPG) coated with alginate, chitosan or trimethyl chitosan (TMC), that are able to penetrate through the nasal mucosa and offer enhanced penetration over uncoated liposomes when delivered as a dry powder. All the liposome formulations, loaded with BSA as model antigen, were spray-dried to obtain powder size and liposome size in a suitable range for nasal delivery. Although coating resulted in some reduction in encapsulation efficiency, levels were still maintained between 60% and 69% and the structural integrity of the entrapped protein and its release characteristics were maintained. Coating with TMC gave the best product characteristics in terms of entrapment efficiency, glass transition (T(g)) and mucoadhesive strength, while penetration of nasal mucosal tissue was very encouraging when these liposomes were administered as dispersions although improved results were observed for the dry powders.

Pharmaceutical applications of micro-thermal analysis.

Micro-thermal analysis is a recently introduced thermoanalytical technique that combines the principles of scanning probe microscopy with thermal analysis via replacement of the probe tip with a thermistor. This allows samples to be spatially scanned in terms of both topography and thermal conductivity, whereby placing the probe on a specific region of a sample and heating, it is possible to perform localized thermal analysis experiments on those regions. In this minireview, the principles of the technique are outlined and the current uses within the polymer sciences described. Current pharmaceutical applications are then discussed; these include the identification of components in compressed tablets, the characterization of drug-loaded polylactic acid microspheres, the analysis of tablet coats, and the identification of amorphous and crystalline regions in semicrystalline samples. The current strengths and weaknesses of the technique are outlined, along with a discussion of the future directions in which the approach may be taken.

An evaluation of the use of modulated temperature DSC as a means of assessing the relaxation behaviour of amorphous lactose.

PURPOSE: To evaluate the use of Modulated Temperature DSC (MTDSC) as a means of assessing the relaxation behaviour of amorphous lactose via measurement of the heat capacity, glass transition (Tg) and relaxation endotherm. METHODS: Samples of amorphous lactose were prepared by freeze drying. MTDSC was conducted using a TA Instruments 2920 MDSC using a heating rate of 2 degrees C/minute, a modulation amplitude of +/-0.3 degrees C and a period of 60 seconds. Samples were cycled by heating to 140 degrees C and cooling to a range of annealing temperatures between 80 degrees C and 100 degrees C, followed by reheating through the Tg region. Systems were then recooled to allow for correction of the Tg shift effect. RESULTS: MTDSC enabled separation of the glass transition from the relaxation endotherm, thereby facilitating calculation of the relaxation time as a function of temperature. The relative merits of using MTDSC for the assessment of relaxation processes are discussed. In addition, the use of the fictive temperature rather than the experimentally derived Tg is outlined. CONCLUSIONS: MTDSC allows assessment of the glass transition temperature, the magnitude of the relaxation endotherm and the value of the heat capacity, thus facilitating calculation of relaxation times. Limitations identified with the approach include the slow scanning speed, the need for careful choice of experimental parameters and the Tg shift effect.

The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze dried systems.

Many pharmaceuticals, either by accident or design, may exist in a total or partially amorphous state. Consequently, it is essential to have an understanding of the physico-chemical principles underpinning the behaviour of such systems. In this discussion, the nature of the glassy state will be described, with particular emphasis on the molecular processes associated with glass transitional behaviour and the use of thermal methods for characterising the glass transition temperature, Tg. The practicalities of such measurements, the significance of the accompanying relaxation endotherm and plasticization effects are considered. The advantages and difficulties associated with the use of amorphous drugs will be outlined, with discussion given regarding the problems associated with physical and chemical stability. Finally, the principles of freeze drying will be described, including discussion of the relevance of glass transitional behaviour to product stability.