The influence of carrier and drug morphology on drug delivery from dry powder formulations

Hassan Larhrib, Gary Peter Martin, Christopher Marriott, David Prime

Research output: Contribution to journalArticlepeer-review

150 Citations (Scopus)


Lactose was crystallised either from neutralised Carbopol 934 gel or from water-ethanol solution without stirring, with a view to obtaining lactose α-monohydrate of favourable shape and smooth surface, suitable for use as carriers in formulations for dry powder inhalers (DPIs). Crystallisation of salbutamol sulphate was carried out in the presence of water, lecithin and ethanol to form salbutamol crystals with defined shape and smooth surface. The crystals formed were needle-shaped, with a length of less than 6μm and a width between 0.5 and 1μm. DSC and TGA showed that lactose crystals produced from Carbopol gel or from water-ethanol solution existed as α-lactose monohydrate. The DSC thermograms of micronised and crystallised salbutamol sulphate showed two similar endothermic transitions at 200 and 290°C, respectively. The first transition was initially thought to correspond to the melting of salbutamol sulphate. However, the shape of the particles as observed by optical microscopy was not altered after heating the sample to 250°C, suggesting that no transition from solid to liquid state occurred at 200°C. This was confirmed by observations made using hot stage microscopy. The two endothermic transitions are suggested to correspond to the decomposition of the salbutamol sulphate molecule. The elongation ratio of the commercial lactose crystals, lactose crystallised from Carbopol and from water-ethanol were 1.69±0.05, 2.01±0.13 and 6.25±0.17, respectively. As the elongation ratio increased the flow properties of the carrier were affected detrimentally and this consequently reduced the content uniformity of salbutamol sulphate and drug emission from the inhaler device. Whereas, increasing the elongation ratio of the carrier or drug improved the deposition profiles of salbutamol sulphate, suggesting that the more elongated particles would be more aerodynamic and favour deep lung penetration.

Original languageEnglish
Pages (from-to)283-296
Number of pages14
JournalInternational Journal of Pharmaceutics
Issue number1-2
Early online date1 Apr 2003
Publication statusPublished - 12 May 2003
Externally publishedYes


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