Microparticle surface layering through dry coating: impact of moisture content and process parameters on the properties of orally disintegrating tablets

Objectives: The aim of this study was to investigate the influence of process parameters during dry coating on particle and dosage form properties upon varying the surface adsorbed moisture of microcrystalline cellulose (MCC), a model filler/binder for orally disintegrating tablets (ODTs). Methods: The moisture content of MCC was optimised using the spray water method and analysed using thermogravimetric analysis. Microproperty/macro-property assessment was investigated using atomic force microscopy, nano-indentation, scanning electron microscopy, tablet hardness and disintegration testing. Key findings: The results showed that MCC demonstrated its best flowability at a moisture content of 11.2% w/w when compared to control, comprising of3.9% w/w moisture. The use of the composite powder coating process (without air) resulted in up to 80% increase in tablet hardness, when compared to the control. The study also demonstrated that surface adsorbed moisture can be displaced upon addition of excipients during dry processing circumventing the need for particle drying before tabletting. Conclusions: It was concluded that MCC with a moisture content of 11% w/w provides a good balance between powder flowability and favourable ODT characteristics

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying

ESPT of 2-(2'-pyridyl)benzimidazole at the micelle-water interface: Selective enhancement and slow dynamics with sodium dodecyl sulfate

The effect of micellar environment on the excited state proton transfer (ESPT) of 2-(2'-pyridyl)benzimidazole (2PBI) has been investigated by steady state and time resolved fluorescence spectroscopy. The ESPT, which occurs to a rather small extent at pH 7, is found to be enhanced remarkably at the interface of sodium dodecyl sulfate (SDS) micelles and water. Such an enhancement is not observed for the cationic cetyl trimethyl ammonium bromide (CTAB) or neutral Triton X-100 micelles. This selective enhancement is explained in the light of a modification of pK(a) and a more acidic local pH in the micelle-water interface. A rise time of about 890 ps is observed in the region of tautomer emission. The origin of this rise time is explored, considering three factors, namely, diffusion controlled protonation of the normal form of 2PBI, slow and possibly incomplete solvation of the transition state, leading to a slowing down of the proton transfer process and a similar slow dynamics of the tautomeric excited state

Hydroxy-terminated conjugated polymer nanoparticles have near-unity bright fraction and reveal cholesterol-dependence of IGF1R nanodomains.

Fluorescent nanoparticles have enabled many discoveries regarding how molecular machines function. Quantum dots have been the dominant class of fluorescent nanoparticles but suffer from blinking and from a substantial dark fraction--particles where the fluorescence is never seen--complicating any analysis of biological function. Nanoparticles composed of conjugated fluorescent polymers (Pdots) have recently been shown to have high brightness and no blinking. Here we develop a robust and efficient means to measure the dark fraction of Pdots, conjugating Atto dyes to the nanoparticles and testing fluorescence colocalization of dye and Pdot puncta. This established that the Pdots we generated had minimal dark fraction: ∼3%. The application of nanoparticles in biological environments is highly sensitive to surface functionalization. For Pdots we found that passivation with uncharged hydroxy-terminated polyethylene glycol caused a dramatic reduction in nonspecific cell binding and aggregation compared to a charged coating. Using carbonyl di-imidazole the hydroxy-Pdots were functionalized efficiently with streptavidin for high stability targeting, allowing specific labeling of mammalian cells. Type I insulin-like growth factor receptor (IGF1R) regulates cell survival and development, with roles in aging, heart disease, and cancer. We used hydroxy-Pdots to track the dynamics of IGF1R on a breast cancer cell-line, determining the diffusion characteristics and showing cholesterol-containing membrane nanodomains were important for receptor mobility at the plasma membrane. The near-unity bright fraction and low nonspecific binding of hydroxy-Pdots, combined with Pdot photostability and lack of blinking, provides many advantages for investigations at the single molecule level

Anomalous excited-state dynamics of Lucifer yellow CH in solvents of high polarity: Evidence for an intramolecular proton transfer

The photophysics of the fluorescent probe Lucifer yellow CH has been investigated using fluorescence spectroscopic and computational techniques. The nonradiative rate is found to pass through a minimum in solvents of intermediate empirical polarity. This apparently anomalous behavior is rationalized by considering the possibility of predominance of different kinds of nonradiative processes, viz. intersystem crossing (ISC) and excited-state proton transfer (ESPT), in solvents of low and high empirical polarity, respectively. The feasibility of the proton transfer is examined by the structure determined by the density functional theory (DFT) calculations. The predicted energy levels based on the time-dependent density functional theory (TD-DFT) method in the gas phase identifies the energy gap between the S-1 and nearest triplet state to be close enough to facilitate ISC. Photophysical investigation in solvent mixtures and in deuterated solvents clearly indicates the predominance of the solvent-mediated intramolecular proton transfer in the excited state of the fluorophore in protic solvents