Catalog NumberHG5989811
CAS Number5989-81-1
CategoryNon-ionic Surfactants
Alpha-Lactose Monohydrate Roller Compaction Modification for Direct Compression Tableting
Abu Fara, Deeb, et al. Drug Development and Industrial Pharmacy 44.12 (2018): 2038-2047.
Roller compaction was investigated as a processing technique to enhance the direct compression properties of crystalline alpha-lactose monohydrate by partially converting it to an amorphous form, offering an alternative to spray-dried lactose as a pharmaceutical excipient.
Experimental Protocol: Crystalline alpha-lactose monohydrate (3.0 kg) was compacted using a production-scale roller compactor at pressures from 1000 to 20000 kPa, with 1-4 compaction repetitions and screw-to-roller speed ratios (SR) from 3 to 10. Compacted sheets were milled and sieved (2000 micron). Crystallinity was quantified by XRPD using a calibration curve from physical mixtures of crystalline and freeze-dried amorphous lactose (relative total peak area method). Additional characterization included SEM, FTIR, Karl Fischer titration, bulk/tapped density, specific surface area (BET), and powder flow indices (Carr index, Hausner ratio).
Performance Evaluation: XRPD analysis demonstrated that roller compaction at 20000 kPa reduced crystallinity to a level comparable to spray-dried lactose and a 75% crystalline/25% amorphous physical mixture. Compaction pressure and repetition were the dominant factors: three compactions at 20000 kPa with SR = 5 yielded approximately 40-50% reduction in crystallinity. FTIR confirmed no chemical isomerization occurred. SEM revealed conversion of torpedo-shaped crystals to cylindrical forms with rounded edges. Bulk density increased from 0.543 to 0.647 g/cm3, and powder flow improved from "fair" to "excellent" per USP 31 classification. Two compactions were sufficient for crystallinity reduction; additional repetitions provided only marginal benefit.
Alpha-Lactose Monohydrate Crystallization and Relaxation Kinetics Under Temperature and Humidity Exposure
Sanchez-Valencia, Andrea, et al. International Journal of Pharmaceutics (2026): 126710.
Two kinetic processes-crystallization and relaxation-were identified and characterized in pharmaceutical-grade alpha-lactose monohydrate upon exposure to controlled temperature and relative humidity conditions, providing mechanistic insight into excipient aging behavior.
Experimental Protocol: Two inhalation-grade lactose materials (fines, D50 = 5.14 um; carrier, D50 = 49.9 um) were stored at ambient (approx. 25 degrees C), 40 degrees C, and 50 degrees C at controlled RH levels (31-94%) for up to 6 months. Samples were characterized at multiple timepoints by BET specific surface area (SSA), laser diffraction particle size distribution, isothermal microcalorimetry (TAM) for amorphous content, SEM, XRPD, DSC, and gravimetric vapor sorption. A two-step kinetic model captured the combined effects.
Performance Evaluation: Amorphous surface regions recrystallized rapidly: at high RH conditions, no detectable amorphicity remained after 1 day, while at 31-33% RH, quantifiable amorphous content persisted beyond 1 month with kinetics accelerated by temperature. Particle size increased at high RH due to aggregation: the fines grade D50 rose from approximately 5.1 um to 11-13 um at 75-94% RH. SSA decreased continuously through both the rapid crystallization phase and a slower long-term relaxation process. The relaxation component was less dependent on temperature and RH and only partially correlated with amorphicity and apparent particle size changes, suggesting crystal defect healing and surface smoothing as the underlying mechanism.
Alpha-Lactose Monohydrate as Inert Grinding Medium in High-Dilution Pharmaceutical Preparation
Kalliantas, D., et al. J. Nanomed 3.1 (2020): 1024.
Alpha-lactose monohydrate was evaluated as a trituration medium in the preparation of ultra-high diluted succussed medicinal products, with the goal of confirming its chemical inertness and physical stability during prolonged hand grinding.
Experimental Protocol: Alpha-lactose monohydrate was triturated alone and with sodium chloride or calcium carbonate (1:9 drug-to-lactose ratio) by hand using unglazed porcelain mortar and pestle for 360 min (up to 6X trituration steps). Samples at initial, 1X, and 6X stages were characterized by SEM, XRD, FTIR, Raman spectroscopy, electrical conductivity, pH measurement, and dynamic light scattering (DLS). Solution preparations were filtered through 200 nm syringe filters prior to analysis.
Performance Evaluation: SEM showed that the tomahawk-shaped lactose crystals retained their morphology throughout trituration, while embedded sodium chloride and calcium carbonate particles were reduced to micro-nanoscale dots firmly attached to the lactose surface. XRD confirmed that alpha-lactose monohydrate maintained its highly crystalline structure with sharp, intense peaks at the 20-degree (2-theta) region at all trituration stages; crystalline signatures of the guest materials were obscured by the dominant lactose signal. FTIR and Raman spectra showed no chemical shifts or new functional groups, confirming the absence of chemical reactions. Electrical conductivity decreased by only 0.28% and pH by 0.057% across trituration steps, attributable primarily to particle size reduction rather than chemical change. DLS confirmed particle size reduction to the micro-nanoscale for guest materials while lactose itself dissolved completely in aqueous solution.