An Investigation into Alternative Sugars as Potential Carriers for a Dry Powder Formulation of Budesonide and Formoterol (original) (raw)
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Investigation into alternative sugars as potential carriers for dry powder formulation of budesonide
BioImpacts : BI, 2011
Dry powder inhaler (DPI) formulations are so far being used for pulmonary drug delivery, mainly for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Currently most of DPI formulations rely on lactose as a carrier in the drug powder blend. However, due to reducing sugar function of lactose which makes it incompatible with some drugs such as budesonide, it is realistic to investigate for alternative sugars that would overcome the concerned drawback but still have the positive aspects of lactose. The study was conducted by characterizing carriers for their physico-chemical properties and preparing drug/carrier blends with concentration of 5% and 10% drug with the carrier. The mixing uniformity (homogeneity) of Budesonide in the blends was analyzed using spectrophotometer. The blend was then filled into NB7/2 Airmax inhaler device and the deposition profiles of the drug were determined using multi stage liquid impinger (MSLI) after aerosolization at 4 kPa via th...
Journal of Pharmaceutical Sciences, 2001
The aim of the study was to investigate the interdependence of carrier particle size, surface treatment of the carrier, and inclusion of fines on the drug delivery from dry power inhaler formulations. Two size fractions (< 63 and 63–90 μm) of α-lactose monohydrate were subjected to treatment with 95% (v/v) ethanol to introduce small asperities or cavities onto the otherwise smooth surface without substantially changing the particle shape. After blending with albuterol sulfate [ALB; volume median diameter (VMD), 1.9 μm; geometric standard deviation (GSD), 1.5], the solvent-treated lactose produced a fine particle fraction (FPF; < 6.18 μm) and dispersibility of the drug that was significantly (ANOVA p < 0.01) lower than that which resulted from formulations containing untreated lactose of a similar size fraction, after aerosolization at 60 L min−1 via a Rotahaler. The two size fractions of the treated lactose resulted in similar deposition profiles of ALB. The effects of such surface asperities or cavities of lactose were offset by introducing a small amount (5% w/w) of smaller-sized lactose (5–10 μm) to the powder formulations. The fine lactose increased the FPF and dispersibility of ALB to such a level that all lactose batches, regardless of particle size or whether solvent treated, produced a similar fraction of aerosolized ALB. The inclusion of recrystallized needle lactose (5–15 μm) was superior to micronized lactose in improving the aerosolization of ALB. The findings of this study indicate that the presence and characteristics of the finer fraction of lactose carrier particles dominate over the particle size and surface smoothness of the carrier particles in determining dispersion and deaggregation of drugs from dry powder formulations for inhalation. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1424–1434, 2001
Effect of Formulation Excipients on Aerosolisation Performance of Budesonide
2017
The marketed dry powder inhalations (DPI) are based on lactose monohydrate alone and lactose anhydrous is neither studied nor used as a carrier in marketed DPIs. Lactose is not recommended as a carrier in budesonide formulations since lactose interacts with amine functional group. This study was carried out to investigate the effect of lactose anhydrous inhalation grade 40 M on the aerosolisation performance of budesonide. The work was also aimed at study of an interaction between budesonide and the lactose carriers in dry state. The powder properties of binary formulations, consisting of lactose anhydrous LA 40M and budesonide, were compared with those of lactose monohydrate LM 40 M and budesonide. In vitro drug release was determined with diffusion cell. Based on the results of the preliminary study, two promising formulations F1 and F2 were subjected to the in vitro deposition study using Twin Stage Impinger and Lupihaler®. The results revealed absence of chemical reaction betwee...
The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance
Pharmaceutical research, 2012
Purpose To obtain crystals with favourable morphological features 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 anti-solvent precipitation technique. The obtained crystals were sieved to separate 63-90 µm size fractions and then characterised in terms of size, shape, density and in vitro aerosolisation performance. Solid state of the 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 the elongation ratio, and increasing the width and thickness of the crystals. Crystallised β-lactose showed different anomer compared to commercial lactose (α-lactose-monohydrate). Also crystallised α-mannitol showed different polymorphic form compared to the commercial mannitol (β-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to α-mannitol, α-lactose-monohydrate, β-lactose, 5α-/3β-lactose and 4α-/1β-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate in comparison to formulations containing commercial. Conclusion The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations.