The purpose of this study was (a) to evaluate the factors affecting the form conversion of anhydrous lactose to the monohydrate form during wet granulation using water as the granulating agent and (b) study the effect of lactose form conversion on its compaction properties. A two-level full factorial design with two center points was used to evaluate the factors affecting form conversion. The three variables evaluated were percentage of microcrystalline cellulose (low 0 and high 20), water to intragranular solids ratio (low 0.10 and high 0.18) and drying conditions (tray drying and fluid bed drying). The presence of microcrystalline cellulose in the formulation did not provide any benefit in reducing the percent lactose conversion. But, the conversion was significantly reduced by decreasing the amount of water added to the granulation and/or by decreasing the drying time, using a fluid bed dryer compared to a tray dryer. In the second part of the study, complete conversion of the anhydrous lactose to monohydrate was achieved by storing the anhydrous form under 25 degrees C/97% RH for 4 weeks. Physical characterization (compactibility, surface area and surface morphology) was performed on the form converted material and compared to the as received anhydrous lactose. The physical characterization results indicated that even though anhydrous lactose undergoes complete form conversion to monohydrate form under high humidity and/or during wet granulation, it retains its inherent higher as received material compactibility and the BET surface area and porosity of the form converted material are higher than that of the as received anhydrous lactose.
[Show abstract][Hide abstract] ABSTRACT: The relationships between the physicochemical properties and functionality in dry powder inhaler (DPI) performance was investigated for inhalation grade anhydrous lactose and compared to monohydrate grades. The excipients were characterised using a range of techniques including particle size analysis, moisture sorption and powder rheometry. The inhalation anhydrous lactose grades were readily characterisable. The aerosolisation performance of capsule based DPI formulations containing budesonide (200microg) and different grades of lactose evaluated using inertial impaction measurements produced fine particle doses of budesonide ranging from 24 to 49microg. There were no apparent relationships between aerosolisation performance and excipient characteristics, such as particle size and powder density. However, formulations containing lactose grades which exhibit higher powder fluidisation energy values resulted in higher fine particle doses of budesonide.
International Journal of Pharmaceutics 05/2010; 390(2):134-41. DOI:10.1016/j.ijpharm.2010.01.028 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The real (ε') and imaginary (ε″) components of the complex permittivity of anhydrous lactose and microcrystalline cellulose (MCC) under different bulk densities, moisture contents (MCs), and times of hydration (for anhydrous lactose) were measured nondestructively using a microwave resonator sensor operating in the range of 700-800 MHz. Measurements of sensor resonant frequency and conductance allow, through calibration, determination of the complex dielectric properties ε' (relative permittivity) and ε″ (relative dielectric loss) of the test material. Characteristic graphs of ε″ versus ε' - 1 curve for each powder were generated as a function of bulk density and MC. Such data can be used to develop empirical models for the simultaneous in situ measurement of the bulk density and MC of the powders. Unlike MCC, anhydrous lactose is converted to its hydrate form in the presence of moisture, which causes a reduction in the amount of physisorbed and "free" water and a subsequent change in the dielectric properties. For powders such as anhydrous lactose that can form a crystal hydrate in the presence of moisture, a combination of techniques such as vibrational spectroscopy together with microwave resonator measurements are appropriate to characterize, in situ, the physical and chemical properties of the powder.
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