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Biomedical subjects

Paul W S Heng

Publications and source records attributed to Paul W S Heng.

11 recordsLinked to original sources

Influence of particle wall adhesion on particle electrification in mixers.

In this work, particle electrification in the Turbula and horizontally oscillating mixers were investigated for adipic acid, microcrystalline cellulose (MCC), and glycine particles. MCC and glycine particles acquired positive electrostatic charges, while adipic acid particles attained negative charges in both mixers. Adipic acid (of sieved size larger than 500 microm), MCC, and glycine particles were monotonically charged to saturated values, and had negligible wall adhesion. On the contrary, the adipic acid particles, both unsieved and sieved but of smaller sieved size fraction, exhibited very different charging kinetics in the horizontally oscillating mixer. These adipic acid particles firstly acquired charges up to a maximum value, and then the charges slowly reduced to a lower saturated value with increasing mixing time. Furthermore, these particles were found to adhere to the inner wall of the mixer, and the adhesion increased with mixing time. Surface specific charge densities for adipic acid particles were estimated based on particle size distribution, and were found to increase with particle mean diameters under the conditions investigated. The results obtained from the current work suggested that electrostatic force enhanced particle-wall adhesion, and the adhered particles can have a significant impact on particle electrification.

Adhesiveness↗

Comparative study of the fluid dynamics of bottom spray fluid bed coaters.

Fluid dynamics of pellets processed in bottom spray traditional Wurster coating and swirl accelerated air (precision) coating were compared with the intent to understand and facilitate improvements in the coating processes. Fluid dynamics was described by pellet mass flow rate (MFR) obtained using a pellet collection system and images captured using high speed photography. Pellet flow within the partition column was found to be denser and slower in Wurster coating than in precision coating, suggesting a higher tendency of agglomeration during the coating process. The influence of partition gap and load on the MFR indicated that the mechanism of transport of pellets into the coating zone in precision coating depended on a strong suction, whereas in Wurster coating, pellets were transported by a combination of peripheral fluidization, gravity, and weak suction pressure. In precision coating, MFR was found to increase uniformly with air flow rate and atomizing pressure, whereas MFR in Wurster coating did not correlate as well with air flow rate and atomizing pressure. This demonstration showed that transport in precision coating was air dominated. In conclusion, fluid dynamics in precision coating was found to be air dominated and dependent on pressure differential, thus it is more responsive to changes in operational variables than Wurster coating.

Capsules↗

New indices to characterize powder flow based on their avalanching behavior.

Use of powder avalanches in the study of flow properties of pharmaceutical excipients has yet to be popularized even though it is rather simple to use and yields comparatively reliable results. Commonly employed flow assessment methods include compressibility studies and shear cell and repose angle measurements. Though widely accepted, these methods are not without limitations and inadequacies. More often than not, experimental and environmental conditions lead to a considerable amount of variability in the results obtained. The primary objective of this current work is to propose two new indices, avalanche flow index (AFI) and cohesive interaction index (CoI) based on the avalanche flow behaviors of powders. Not only were these two indices able to describe the ease of powder flow but they also provided a simpler means of quantifying the extent of cohesive interactions within the powder mass without elaborate mathematical functions.

Algorithms↗

Functionality of cross-linked polyvinylpyrrolidone as a spheronization aid: a promising alternative to microcrystalline cellulose.

PURPOSE: This work seeks to explore and demonstrate the functionality of cross-linked polyvinylpyrrolidone (crospovidone) as a spheronization aid and a promising alternative to microcrystalline cellulose (MCC). METHODS: Pellets were prepared with various grades of crospovidone using both small- and large-scale extrusion-spheronization. A Box-Behnken experimental design was employed to elucidate the effects of operating variables on the quality of the pellets. Size and shape analyses of these pellets were conducted and compared to those prepared using MCC. RESULTS: Crospovidone was believed to behave like a liquid repository in its interaction with water during extrusion-spheronization, although its binding ability was weaker than that of MCC. Spherical pellets of narrow size distribution could be made from the finer crospovidone grades with different lactose grades. However, crospovidone-based formulations required higher water levels than weight-equivalent MCC-based formulations. Crospovidone pellets were of equivalent quality to those prepared with MCC, especially in the shape, size, and yield. CONCLUSIONS: Crospovidone can be successfully employed as a spheronization aid to produce good pellets without the need of a binder, unlike most of the previously proposed materials. This study exemplified the enormous potential of crospovidone to serve as a competent alternative to MCC in the production of pellets by extrusion-spheronization.

Cellulose↗

A novel preformulation tool to group microcrystalline celluloses using artificial neural network and data clustering.

PURPOSE: To group microcrystalline celluloses (MCCs) using a combination of artificial neural network (ANN) and data clustering. METHODS: Radial basis function (RBF) network was used to model the torque measurements of the various MCCs. Output from the RBF network was used to group the MCCs using a data clustering technique known as discrete incremental clustering (DIC). Rheological or torque profiles of various MCCs at different combinations of mixing time and water:MCC ratios were obtained using mixer torque rheometry (MTR). Correlation analysis was performed on the derived torque parameter Torque(max) and physical properties of the MCCs. RESULTS: Depending on the leniency of the predefined threshold parameters, the 11 MCCs can be assigned into 2 or 3 groups. Grouping results were also able to identify bulk and tapped densities as major factors governing water-MCC interaction. MCCs differed in their water retentive capacities whereby the denser Avicel PH 301 and PH 302 were more sensitive to the added water. CONCLUSIONS: An objective grouping of MCCs can be achieved with a combination of ANN and DIC. This aids in the preliminary assessment of new or unknown MCCs. Key properties that control the performance of MCCs in their interactions with water can be discovered.

Cellulose↗

Complexation between PVP and Gantrez polymer and its effect on release and bioadhesive properties of the composite PVP/Gantrez films.

Complexation between poly(methyl vinyl ether-maleic anhydride) copolymer (Gantrez AN 169) and polyvinylpyrrolidone (PVP K-90D) in aqueous solutions were investigated using a viscometric method and Raman spectroscopy. The composite films with different weight ratios of PVP to Gantrez were prepared in the presence of N-methyl-2-pyrrolidone. The release profiles of diclofenac sodium (DS) from these films were determined and the bioadhesive properties measured. An interpolymer complex was formed through hydrogen bonding between the carbonyl groups of PVP and the hydroxyl groups of Gantrez. The formation of interpolymer hydrogen bonds reduced the interaction of the polymers with water molecules, thus resulting in a lower solubility of the complex in water and a further retarded release of DS from the composite films. The interpolymer complexation was also found to increase the bioadhesive properties of the composite films to a silicone elastomer substrate. The complexation of PVP and the Gantrez copolymer in the composite films was a critical factor affecting the release of DS from the films and the bioadhesive properties of the films.

Adhesives↗

Immobilization of fine particles on lactose carrier by precision coating and its effect on the performance of dry powder formulations.

The feasibility of immobilization of fine particles on a lactose carrier by precision coating and producing carrier particles of different surface roughness from the same core was explored. A relationship between the resultant surface roughness of the carrier and the in vitro deposition pattern of salbutamol sulfate was established. Lactose carrier particles in the precision coating chamber were spray coated with liquid suspensions consisting of micronized lactose dispersed in isopropyl alcohol (IPA) and/or water mixtures. The surface-modified lactose particles were fractionated and then characterized by laser diffraction for size, image analysis for shape, and scanning probe microscopy for surface roughness. The in vitro deposition pattern of salbutamol sulfate from the drug-lactose mixtures was determined with the twin-stage glass impinger and expressed as the fine particle fraction and dispersibility of the drug. Immobilization of fine particles on carrier particles was feasible by the precision coating process as shown by the scanning probe topographs and the roughness values of the carrier particles. Generally, more discrete fine particles were deposited on the carrier surface and a higher surface roughness was seen when the spray suspension consisting of a higher proportion of IPA was used. A significant correlation was found between the fine particle fraction of salbutamol sulfate with the roughness of lactose. This relationship established between the in vitro drug deposition pattern and the microscopic surface roughness of the carrier would be helpful in the optimization of drug delivery to targeted areas in the lungs.

Albuterol↗

Buccal delivery systems.

The oral cavity is an attractive site for drug delivery due to ease of administration and avoidance of possible drug degradation in gastrointestinal tract and first-pass metabolism. Buccal drug delivery specifically refers to the delivery of drugs within/ through buccal mucosa to affect local/systemic pharmacological actions. This review briefly describes advantages and limitations of buccal drug delivery, anatomical structure of oral mucosa, and methodology in evaluating buccal drug delivery system, focusing on physiology, pharmacology, pathology, and formulation design in line with recent developments in buccal delivery systems.

Adhesives↗

Use of a fluidized bed hammer mill for size reduction and classification: effects of process variables and starting materials on the particle size distribution of milled lactose batches.

The process capability of a fluidized bed hammer mill was investigated with respect to four process variables, namely, rotational speeds of beater system and classifier wheel, airflow rates and length of grinding zones, as well as the particle size and flow property of the starting materials. The size distributions of all the milled lactose batches could be fitted to the Rosin Rammler distribution (RRD) function. The characteristic particle size (De) and uniform coefficient (n), which were derived from the RRD function, complemented the size at the 99th percentile of the cumulative undersize distribution (D99) to characterize the lactose batches. Lower De and D99 values indicate a finer powder while a higher n value indicates a narrower size distribution. The beater speed played a critical role. Increasing the beater speed from 12000 to 21000 rpm generally resulted in an increase in n and a decrease in D99 values due to the greater amount of milling energy supplied. The particle size and flow property of the starting material also played an important role at beater speed of 12000 rpm, where the lowest amount of milling energy was supplied. When a higher amount of milling energy was provided, the effect of particle size of the starting material was less significant. The other process variables exerted varying effects. Increasing the classifier wheel speed from 5000 to 15000 rpm decreased the De and D99 and increased the n values of the milled lactose batches, provided sufficient milling energy was supplied to the lactose particles. Changing airflow rates from 80 to 90 m3/h generally resulted in larger De and D99 values and lower n values as the higher airflow rate provided greater airflow-induced kinetic energy that facilitated the passage of lactose through the classifier wheel. However, changing the long grinding zone to a short one did not significantly affect the De, D99 and n values of the milled lactose batches produced. Small lactose particles of narrow size distribution could be obtained using the fluidized bed hammer mill upon gaining a better understanding of the milling process.

Air Movements↗

Effects of aldehydes and methods of cross-linking on properties of calcium alginate microspheres prepared by emulsification.

Calcium alginate microspheres were prepared by an emulsification method and cross-linked with various aldehydes using different methods. Methanal and pentanedial produced low aggregation of microspheres while octanal and octadecanal produced the opposite effect. The latter two aldehydes displaced very little calcium ions from the alginate microspheres, indicating that the aggregation was due to the tackiness imparted by the aldehydes to the microsphere surface. Higuchi's model was not applicable to the drug release from microspheres in this study. The microspheres treated with methanal or pentanedial showed comparable dissolution T75% values which were significantly higher than that of the control. In contrast, octanal and octadecanal produced microspheres with lower dissolution T75% values. The drug contents of the microspheres treated with aldehydes were significantly lower than that of the control. There was insignificant interaction between the aldehydes and the drug. However, the aldehydes were found to impart acidity to the aqueous solution to varying extents, resulting in varying drug loss from the microspheres. The properties of the microspheres were also markedly affected by the method of incorporating the aldehyde. Soaking the microspheres in methanal solution produced microspheres with marked aggregation and low drug content.

Aldehydes↗

Influence of storage conditions and type of plasticizers on ethylcellulose and acrylate films formed from aqueous dispersions.

PURPOSE: To investigate the influence of storage conditions and types of plasticizers on the properties and stability of ethylcellulose and polymethacrylate films and to elucidate the mechanism for the changes observed. METHODS: Films were prepared from Surelease, Aquacoat and Eudragit L 30D dispersions by the casting method. The effects of different plasticizers on the morphology, transparency, mechanical property and water vapour permeability of the prepared films were studied. The film samples were exposed to storage conditions of 30 degrees C and 50 or 75 %RH. Samples were removed at pre-determined time intervals for mechanical testing and analysis of plasticizer content in the films. RESULTS: It was found that films prepared from aqueous ethylcellulose dispersions were relatively weaker and more brittle than acrylate films. Acrylate films did not show any significant change in mechanical property when stored at high humidity. However, the properties of ethylcellulose films stored at high humidity varied depending on the type of plasticizers present. CONCLUSIONS: The changes in mechanical property of ethylcellulose films on storage were mainly attributed to the loss of plasticizers during storage, causing further coalescence of ethylcellulose films and to a smaller extent, reduction in moisture content of the film.

Acrylates↗