The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance

Waseem Kaialy, Hassan Larhrib, Gary P. Martin, Ali Nokhodchi

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Purpose To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. Methods Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using antisolvent precipitation technique. Obtained crystals were sieved to separate 63-90 μm size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC. Results At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals' width and thickness. Crystallised ß-lactose showed different anomers compared to commercial lactose (a-lactose monohydrate). Crystallised a- mannitol showed different polymorphic form compared to commercial mannitol (ß-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to a-mannitol, a- lactose monohydrate, ß-lactose, 5a-/3ß-lactose and 4a-/1ß-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers. Conclusion The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.

Original languageEnglish
Pages (from-to)2139-2156
Number of pages18
JournalPharmaceutical Research
Issue number8
Early online date5 Apr 2012
Publication statusPublished - Aug 2012


Dive into the research topics of 'The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance'. Together they form a unique fingerprint.

Cite this