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Spray dried powders for use in dry powder aerosol formation

Chawla, Aneeta; (1993) Spray dried powders for use in dry powder aerosol formation. Doctoral thesis (Ph.D.), University College London (United Kingdom). Green open access

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Abstract

Spray drying was employed as a means of controlled particle size reduction of powders, for use in formulation of therapeutic dry powder aerosols. Spray drying is a process whereby a solution, slurry or suspension is atomised into a fine spray, mixed with warmed air and allowed to evaporate to a dry particulate powder. It has been used successfully by many industries, including the pharmaceutical industry, to produce products of well defined physical and chemical properties. It has the advantage of being a simple one stage process, for which the operation variables can be accurately controlled and if necessary fully automated. The drugs; isoprenaline sulphate and hydrochloride, salbutamol base and sulphate and pentamidine isethionate were preliminarily investigated, from which salbutamol sulphate was chosen as a model drug for further studies. The spray drying process was optimised, in terms of particle size and percentage yield, for salbutamol sulphate using 24 factorial design analysis, investigating the pump speed, aspirator level, heat control level and feed concentration. Physical properties, important for dry powder aerosol formulation, of spray dried salbutamol sulphate, were investigated and compared to those of the micronised drug usually used in this type of formulation. The properties investigated were as follows: powder flow expressed in terms of flow parameters such as angle of repose, angle of spatula, compressibility (Carr's compressibility ratio) and cohesion/uniformity; particle size, measured by scanning microscopy, computer image analysis and laser diffraction; size distribution, measured by laser diffraction; shape, evaluated using computer image analysis; apparent density, measured using an air comparison pycnometer, crystallinity, evaluated by x-ray diffraction and in vitro lung deposition, evaluated using the twin impinger and cascade impactor apparatus. Spray drying was seen to produce spherical, amorphous particles of narrow size distribution suitable for inhalation, that is below 10 ?m. Spray drying did not alter the chemical nature, determined by infra red spectroscopy or affect substantially drug potency, determined by fluorospectroscopy. It did however alter the crystallinity, shown by x-ray diffraction. The surface energies of both spray dried and micronised salbutamol sulphate forms, together with lactose, medium grade and spray dried, were calculated from contact angle measurements, made using the Wilhelmy gravitational method. These were then used in the determination of polarity, work of adhesion, work of cohesion and spreading coefficients of the materials. The results of which were discussed in connection with powder properties of flow and in vitro deposition. This preliminary work showed, within the limitations of the experimentation, surface energy, work of adhesion, work of cohesion and spreading coefficient to have potential in the prediction of powder behaviour and interaction of powders, in dry powder aerosol formulation, including the liberation of the drug from inert carriers.

Type: Thesis (Doctoral)
Qualification: Ph.D.
Title: Spray dried powders for use in dry powder aerosol formation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: (UMI)AAI10104286; Health and environmental sciences; Pharmaceutical powders; Spray drying
URI: https://discovery.ucl.ac.uk/id/eprint/10109581
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