Chinmay Ghoroi

Passivation of High-Surface-Energy Sites of Milled Ibuprofen Crystals via Dry Coating for Reduced Cohesion and Improved Flowability

Ibuprofen micronization with dry coating is investigated to examine its influence on passivation/stabilization of high-surface-energy sites and reduced cohesion. A fluid energy mill was used to micronize ibuprofen particles down to 5-28 μm with or without simultaneous nanosilica coating. Powder flow property and dispersibility were characterized using FT4 powder tester and Rodos/Helos laser diffraction particle sizer. Surface energy was characterized using a next generation inverse gas chromatography instrument. Uncoated micronized ibuprofen showed an increased Lifshitz-van der Waals (LW) dispersion component of surface energy with increasing milling intensity. In contrast, dry-coated milled powders showed a significant reduction in the LW component, whereas physical mixture of uncoated micronized ibuprofen and silica exhibited no reduction in surface energy, indicating that dry coating is necessary for the passivation of high-energy sites of ibuprofen created during micronization. Surface energy of pure micronized ibuprofen was highly heterogeneous, whereas dry-coated ibuprofen had greatly reduced heterogeneity. Micronization with dry coating also improved flowability and bulk density as compared with pure active pharmaceutical ingredient micronization without coating, or just blending with silica. Overall, dry coating leads to decreased cohesion and improved flowability because of reduced LW dispersive component of surface energy and creating nanoscale surface roughness.

Influence of surface modification on wettability and surface energy characteristics of pharmaceutical excipient powders

Influence of surface modification on wettability and surface energy characteristics of three micron size pharmaceutical excipient powders was studied using hydrophilic and hydrophobic grades of nano-silica. The wetting behavior assessed from contact angle measurements using sessile drop and liquid penetration (Washburn) methods revealed that both techniques showed similar wettability characteristics for all powders depending on the hydrophilic or hydrophobic nature of nano-coating achieved. The polar (γs(p)) and dispersive (γs(d)) components of surface energies determined using extended Fowkes equation with contact angle data from sessile drop method and inverse gas chromatography (IGC) at infinite dilution suggested a general trend of decrease in γs(d) for all the surface modified powders due to passivation of most active sites on the surface. However, depending on the nature of the functional groups present in nano-silica, γs(p) was found to be either higher or lower for hydrophilic or hydrophobic coating respectively. Results show that wettability increases with increasing γs(p). Both the techniques of surface energy determination provided comparable and similar trends in γs(p) and γs(d) components of surface energies for all excipients. The study also successfully demonstrated that surface wettability and energetics of powders can be modified by varying the level of surface coating.

Influence of particle properties on powder bulk behaviour and processability

Understanding interparticle interactions in powder systems is crucial to pharmaceutical powder processing. Nevertheless, there remains a great challenge in identifying the key factors affecting interparticle interactions. Factors affecting interparticle interactions can be classified in three different broad categories: powder properties, environmental conditions, and powder processing methods and parameters. Although, each of these three categories listed is known to affect interparticle interactions, the challenge remains in developing a mechanistic understanding on how combination of these three categories affect interparticle interactions. This review focuses on the recent advances on understanding the effect of powder properties, particularly particle properties, its effect on interparticle interactions and ultimately on powder bulk behaviour. Furthermore, this review also highlights how particle properties are affected by the particle processing route and parameters. Recent advances in developing a particle processing route to prepare particles with desired properties allowing desired interparticle interaction to deliver favoured powder bulk behaviour are also discussed. Perspectives for the development of potential particle processing approaches to control interparticle interaction are presented.

Fine powder flow under humid environmental conditions from the perspective of surface energy

The influence of humidity on surface energetics and flow behavior of fine pharmaceutical powders was investigated. Amorphous and crystalline fine powders with hydrophilic (Corn starch and Avicel PH105) and hydrophobic (ibuprofen) nature were considered for this study. The surface energy was determined using surface energy analyzer and flow behavior was measured in terms of unconfined yield stress (UYS) using a shear tester. The study showed that unlike hydrophobic ibuprofen powder, surface energy and flow of hydrophilic excipient powders were affected by relative humidity (RH). The Lifshitz-van der Waals dispersive (γ(LW)) component of surface energy barely changed with varying RH for all pharmaceutical powders. For hydrophilic excipients, the specific component of surface energy (γ(SP)) was found to increase with increasing RH. Furthermore, for these excipients, flow deterioration at elevated RH was observed due to increased capillary bridge formation. Detailed analysis showed that γ(SP) component of surface energy can be an effective indicator for flow behavior of fine powders under varying humid conditions. The present study also brought out the existence of different regimes of probable interparticle forces which dictate the bulk flow behavior of fine hydrophilic powder under humid conditions.

Wettability measurement apparatus for porous material using the modified Washburn method

In this work a cost-effective instrument for measuring the wettability of powder materials was designed and developed, which works on the modified Washburn method. The instrument measures the mass gain against time due to penetration of the liquid into the powder materials using a microbalance and LabVIEW-based data acquisition system. The wettability characteristic of different powders was determined from the contact angle using the modified Washburn equation. To demonstrate the performance of the developed instrument, the wettability of as-received corn starch and nano-coated corn starch powders was estimated with water as a test liquid. The corn starch powders coated with hydrophilic grade (Aerosil 200P) and hydrophobic grade (Aerosil R972) nanoparticles at different coating levels showed expected changes in their contact angle. Some of the results were also verified against the available standard instrument for wettability measurement and found to be consistent. The present configuration of the instrument costs about 500 US

Effect of temperature on the surface free energy and acid–base properties of Gabapentin and Pregabalin drugs − a comparative study

which is 15 to 20 times less than the available advanced models. The developed instrument is thus a cost-effective solution for wettability measurement which can be used for materials in food processing, pharmaceuticals, horticulture, textile manufacturing, civil engineering etc. The developed instrument is expected to help many small scale industries or research labs who cannot afford an expensive instrument for wettability studies.

Improving the wetting and dissolution of ibuprofen using solventless co-milling

The surface energetics of Gabapentin (GBP) [2-[1-(aminomethyl) cyclohexyl] acetic acid] and Pregabalin (PGB) [(S)-3-(aminomethyl)-5-methylhexanoic acid] were studied using a surface energy analyzer (SEA); a new-generation inverse gas chromatography technique, in the temperature range of 298.15–323.15 K. The Lifshitz–van der Waals dispersive (γds) component of the surface energy was calculated using Schultz and Dorris-Gray methods. The specific free energy of adsorption (ΔGspa) and specific component of surface free energy (γsps) were determined using Schultz and Polarization methods. For both the drugs, the γds component of the surface energy was found to decrease with the increase in temperature. The γds component of the surface energy obtained for GBP and PGB surfaces suggested that GBP is slightly more energetically active than PGB. However, the PGB surface showed slightly higher γsps implying its more polar nature as compared to GBP. These drugs with different structures but identical functional groups (–NH2 and –COOH), were found to have a higher surface Lewis base parameter, (Kb), indicating predominately basic surfaces. Furthermore, the temperature dependence of the Lewis acid–base parameters for these drugs was attributed to the disruption of intramolecular hydrogen bonding at higher temperatures.

Characterisation of bulk and shear properties of basmati and non-basmati rice flour

The wetting and dissolution of a BCS class II drug (Ibuprofen) is enhanced by solventless solid dispersion technique using co-milling. The co-milling is performed in a planetary ball mill using 1:1wt. ratio of Ibuprofen (drug) and Microcrystalline cellulose, MCC (excipient). The improvement in wettability and dissolution after co-milling are compared with the raw ibuprofen, ball-milled ibuprofen without any excipient and v-blend mixture of ibuprofen with an excipient. The changes in crystal level properties and reduction in crystallinity due to co-milling are measured using Powder X-ray diffraction (P-XRD) and Differential Scanning Calorimetry (DSC) respectively. The increased interaction between ibuprofen and MCC as well as hydrogen bond formation is confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The morphological changes are observed by optical microscopy and Field Emission Scanning Electron Microscopy (FESEM). The miscibility of drug and excipient and evidence of formation of glassy solutions are demonstrated by Modulated Temperature Differential Scanning Calorimetry (MTDSC) and Raman microscopy. The surface energy and wetting properties are determined using Inverse Gas Chromatography (IGC) and sessile drop method respectively. The results show that co-milling generates defects, strain, and reduction in crystallite size (changes in crystal level properties) which are responsible for the improvement of wetting and dissolution (96% in 90min). Also, with increase in co-milling time, the polar surface energy increases and the hydrophobic ibuprofen drug surface transforms into hydrophilic surface due to increase in OH groups of MCC on the ibuprofen surface. The present work quantified all the above-mentioned parameters including the acidic and basic parameters of co-milled ibuprofen using IGC. The technique improves the wetting and dissolution of hydrophobic drugs. It can be very well extended to BCS class II and IV drugs in the presence of different hydrophilic excipients.

Influences of Crystal Anisotropy in Pharmaceutical Process Development

BACKGROUND Flours are often unstable in relation to their flow performance, which is evident when a free-flowing material ceases to flow and the processing, handling, and production parameters depend on the inherent powder characteristics and their bulk behaviour. The present study was conducted to compare the flowability of basmati and non-basmati rice flour affecting bulk handling, which could be related to its particle size, shape and surface roughness (measured by atomic force microscopy) as well as bulk and shear properties, depending upon the processing conditions. RESULTS Particle size (171.1-171.9 μm) of both samples was not significantly different. However, the flowability of the non-basmati rice flour was significantly affected by its particle shape (circularity 0.487), surface roughness (124.23 nm) and compressibility (25.32%) in comparison to basmati rice flour (circularity 0.653, surface roughness 113.59 nm and compressibility 21.09%), making it more cohesive than basmati rice flour. Also, basic flow energy was significantly higher in non-basmati flour, thus requiring more energy (147.54 mJ) to flow than basmati rice flour (130.15 mJ). CONCLUSION Overall, flowability was analysed by applying three different pressures (3, 6 and 9 kPa), among which non-basmati rice flour was found to be less flowable (flow function coefficient (FFC) 2.33 at 9 kPa) in comparison to basmati (FFC 3.35 at 9 kPa), making bulk handling difficult. This study could be useful in designing processing equipment, hoppers and silos for rice flour handling.

Conversion of a CNG Powered Auto Rickshaw to an Electric Rickshaw Designed for Indian Conditions

Crystalline materials are of crucial importance to the pharmaceutical industry, as a large number of APIs are formulated in crystalline form, occasionally in the presence of crystalline excipients. Owing to their multifaceted character, crystals were found to have strongly anisotropic properties. In fact, anisotropic properties were found to be quite important for a number of processes including milling, granulation and tableting. An understanding of crystal anisotropy and an ability to control and predict crystal anisotropy are mostly subjects of interest for researchers. A number of studies dealing with the aforementioned phenomena are grounded on over-simplistic assumptions, neglecting key attributes of crystalline materials, most importantly the anisotropic nature of a number of their properties. Moreover, concepts such as the influence of interfacial phenomena in the behaviour of crystalline materials during their growth and in vivo, are still poorly understood. The review aims to address concepts from a molecular perspective, focusing on crystal growth and dissolution. It begins with a brief outline of fundamental concepts of intermolecular and interfacial phenomena. The second part discusses their relevance to the field of pharmaceutical crystal growth and dissolution. Particular emphasis is given to works dealing with mechanistic understandings of the influence of solvents and additives on crystal habit. Furthermore, comments and perspectives, highlighting future directions for the implementation of fundamental concepts of interfacial phenomena in the rational understanding of crystal growth and dissolution processes, have been provided.