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Biomedical subjects

P W Heng

Publications and source records attributed to P W Heng.

At least 19 recordsLinked to original sources
PubMed2001

Investigation of the influence of mean HPMC particle size and number of polymer particles on the release of aspirin from swellable hydrophilic matrix tablets.

The effects of hydroxypropyl methylcellulose (HPMC) of different particle size ranges, size distributions and concentrations on the release behaviour of aspirin from a swellable matrix tablet system were studied. A mean HPMC (Methocel K15M Premium) particle size of 113 microm was identified as a critical threshold in this study. Drug release rate increased markedly when polymer particle size was increased above 113 microm. Release rate was much less sensitive to changes in particle size below 113 microm. Aspirin release mechanism followed first order kinetics where mean HPMC particle size was below 113 microm. Release mechanism deviated from first order kinetics when the mean particle size was above 113 microm. Polymer fractions with similar mean particle size but differing size distribution were also observed to influence drug release rate but not release mechanism. First order release constant K(1) was found to be quantitatively related to the reciprocal of the cube root of both mean polymer particle size and number of polymer particles in the matrix.

Aspirin↗
PubMed2001

An improved method for the measurement of colour uniformity in pellet coating.

Sucrose pellets in the size range of 0.71--0.85 mm were film-coated in a bottom-spray Wurster fluidised bed coater with a colour coating suspension of 7.5% w/w solids. Hydroxypropyl methylcellulose was used as a film former, polyethylene glycol as a plasticiser and yellow iron oxide as a coloured pigment. The colour distribution on the film coat was analysed using a tristimulus colorimeter and the colour value was measured in CIELAB units. Uniformity in the colour coat was indicated by the standard deviation of the colour measurement values. Four different methods for measuring the colour distribution over the colour coated pellets' surfaces were carried out. In method I, colour measurements of the pellets' surfaces were made by placing the pellets directly on the stage of the tristimulus colorimeter. A specially designed pellet sample holder was employed to assist the collection of colour measurements in methods II--IV. Colour measurements from eight spots on each pellet were taken in methods I, II and IV while method III involved measuring 24 spots per pellet. A total of eight overlapping spot measurements were taken in method IV while the eight spot measurements in method II were non-overlapping. Method II was found to be the most efficient, accurate and sensitive method for the measurement of spot colour distribution on pellets.

Algorithms↗
PubMed2001

A study of the effects of the physical characteristics of microcrystalline cellulose on performance in extrusion spheronization.

PURPOSE: Physical characterization and extrusion-spheronization profiles of 11 microcrystalline cellulose (MCC) grades were performed. Correlation between the physical characteristics and extrusion spheronization behavior and pellet quality was performed to determine critical MCC characteristics that influence the water requirement and spheronization water sensitivity for extrusion-spheronization. METHODS: Extrusion spheronization of MCC-lactose at varying water contents was performed to determine water requirement, spheronization water sensitivity, and the effect of increasing water content on some pellet qualities (pellet flow rate, friability, bulk, and tapped densities) of each MCC grade. MCC physical properties and tapping characteristics were assessed. Correlation between MCC physical properties and its spheronization behavior parameters was performed. RESULTS: MCC characteristics, such as powder particle size, size distribution, and porosity, were found to have little influence on the extrusion-spheronization process. However, significant correlation was found between void volumes or packing properties of MCC and the water requirement for extrusion-spheronization and pellet qualities. CONCLUSIONS: A new insight into the action of MCC as a spheronizing aid was discovered. MCC void volume and packing properties play an important role in determining water retention and release during extrusion-spheronization.

Cellulose↗
PubMed2001

The influence of microcrystalline cellulose grade on shape and shape distributions of pellets produced by extrusion-spheronization.

In this study, five microcrystalline cellulose (MCC) grades were physically characterized and their extrusion-spheronization behaviours were characterized in terms of water requirements and pellet shape profiles. It was found that the MCC grades differed significantly in the physical properties investigated. Physical properties of MCC were found to influence the water requirement for extrusion-spheronization. MCC grades of higher bulk densities, lower porosities and water retentive capacities required less water to produce pellets of equivalent size. These MCC grades were also found to produce pellets of lower sphericity and wider shape distributions. Packing of MCC particles within the agglomerate played a role in determining amount of water retention and pellet rounding during spheronization. However, there was a limit to the influence of packing density on the rate of pellet rounding because poor packing resulted in higher water retentive capacity, which also limited the rate of rounding.

Cellulose↗
PubMed2000

Role of base plate rotational speed in controlling spheroid size distribution and minimizing oversize particle formation during spheroid production by rotary processing.

The occurrence of material adhesion and formation of oversize particles in the product yield during one-pot spheroid production by rotary processing leads to a less predictable process and a decrease in the usable portion of the total product yield obtained from each production run. The use of variable speeds of the rotating frictional base plate during the spheronization run was investigated for achieving optimal spheroid production. When the base plate speed was increased during liquid addition, the greater centrifugal forces generated improved liquid distribution and the mixing of the moist powder mass, resulting in a decrease in the amount of oversize particles formed. When the base plate was maintained at a high speed throughout the run, the amount of oversize particles and mean spheroid size increased, and a greater "between batch" mean spheroid size variability was also observed. The findings showed that, when higher speeds were used, the residence time must be adjusted accordingly to avoid excessive coalescence and growth while maintaining even liquid distribution. A "low-high-low" speed variation during rotary processing may be used to produce spheroids with a narrow size distribution and with a minimal amount of oversize particles in the total product yield.

Adsorption↗
PubMed2000

Study of the melt pelletization process focusing on the micromeritic property of pellets.

Melt pelletization of lactose 450 M was carried out in an 8-l high shear mixer using PEG 3000 as the meltable binder. The pore size and size distribution of the melt pellets were determined using mercury intrusion porosimetry. The pore size distribution of melt pellets was found to be bimodal. With a higher binder concentration, post-melt impeller speed or longer post-melt processing time, the fraction of large pores in the agglomerates was reduced but the tendency of the agglomerates to develop sub-micron pores increased. The extent of formation of large pores was dependent on the interplay between the inter-particle distance of lactose particles and the contraction property of molten binder. High process temperature was associated with a greater amount of water loss from the melt agglomerates. The water vapor liberated from the lactose particles, was trapped in the molten PEG during the pelletization process. The formation of sub-micron pores was a result of escape of this water vapor on solidification of the molten PEG as well as agglomerate densification. The quantity of sub-micron pores produced was found to be related to the level of water loss. The melt agglomeration gave rise to large agglomerates when long post-melt processing time, high post-melt impeller speed or binder concentration was used.

Drug Compounding↗
PubMed2000

Quantification of the surface morphologies of lactose carriers and their effect on the in vitro deposition of salbutamol sulphate.

Application of the scanning probe microscopy technique for quantitative measurement of the surface roughness of lactose carriers was evaluated. The roughness values of four different lactose carriers were related to the in vitro deposition results of the drug, salbutamol sulphate. The rugosity values of the lactose carriers were represented by Ra values which were in the order of DCL-40>DCL-11>lactose 325M>lactose 200 M. In vitro deposition results using a twin impinger showed that rougher carrier surfaces generally allowed more drug particles to be emitted from the capsules and inhaler but the availability of the drug to stage 2 was reduced, as detachment of drug particles from the carrier surfaces was more hindered. There was an optimum Ra value for greater delivery of the drug particles to stage 2 of the twin impinger. A balance between adherence and detachment of the drug from the carrier surface was needed in order to optimize the delivery of a drug to the desired target sites using a dry powder inhaler.

Adrenergic beta-Agonists↗
PubMed2000

Influence of production variables on the sphericity of melt pellets.

This paper reports the influence of post-melt impeller speed, post-melt processing time, binder concentration and particle size of bulk material on the sphericity of pellets produced by melt pelletization in a high shear mixer. Lactose was used as the bulk material with polyethylene glycol 3000 as a meltable binder. The sphericity of pellets was found to be affected by post-melt impeller speed and post-melt processing time. Binder concentration and particle size of bulk material had a lesser effect on pellet sphericity. The melt pelletization process can be divided into two spheronization phases (a fast initial rate, followed by a slower rate). The change in the spheronization rate was associated with the pellet size, porosity and flow pattern of the processing material. The present study established a bi-exponential mathematical model to relate the pellet sphericity with post-melt specific energy consumption. The relationship of pellet sphericity with post-melt specific energy consumption was independent of the effects of the production variables.

Delayed-Action Preparations↗
PubMed2000

Total intravenous anaesthesia using 3-in-1 mixture of propofol, alfentanil and mivacurium.

INTRODUCTION: To avoid errors and confusion associated with 3 separate infusions, we conducted a feasibility study of total intravenous anaesthesia (TIVA) using 1 electrically-powered syringe pump to deliver a 3-in-1 mixture containing fixed proportions of propofol, alfentanil and mivacurium. MATERIALS AND METHODS: The 3-in-1 mixture was obtained by mixing 200 mg propofol, 1 mg alfentanil, 20 mg mivacurium, and making up to 40 mL with 5% dextrose solution. Electrical zone sensing sizer and light microscopy were used to compare emulsion instability of the 3-in-1 with control mixtures. In 50 ASA 1 patients, bolus infusions of 0.4 mL of the 3-in-1 mixture per kg body weight were given for induction of anaesthesia. All patients were subsequently intubated and ventilated with air-oxygen mixtures. Anaesthesia was maintained using a continuous infusion of the 3-in-1 mixture with the infusion rate titrated to satisfactory clinical response. Intravenous morphine 0.1 mg/kg was given for intra- and postoperative analgesia. Residual neuromuscular blockade was reversed using glycopyrronium and neostigmine at the end of surgery. RESULTS: The 3-in-1 mixtures remained stable for up to 5 hours after preparation. Induction and maintenance of anaesthesia were smooth, intubation conditions satisfactory, and intraoperative haemodynamic changes acceptable. Recovery from anaesthesia and neuromuscular blockade was rapid. There were no major intra- or immediate postoperative complications. CONCLUSIONS: The 3-in-1 mixtures remained stable for up to 5 hours after preparation. It may be feasible to provide TIVA using the 3-in-1 mixture for induction and maintenance of anaesthesia in ASA 1 patients.

Adult↗
PubMed1999

Effect of off-bottom clearance on properties of pellets produced by melt pelletization.

This study examines the influence of off-bottom clearance on size and size distribution of pellets produced during melt pelletization at different postmelt impeller speeds and binder concentrations using lactose and polyethylene glycol. Melt pelletization of lactose powder 450 M in an 8-liter highshear mixer, the floor of which was made of polytetrafluoroethylene (PTFE), was carried out with polyethylene glycol 3000 as the meltable binder. Erosion of the PTFE floor of the mixer occurred with time of use and this caused a change in the off-bottom clearance. The findings showed that with a wider clearance, the size distribution of pellets was wider and pellets were much larger. These changes were the results of changes in the mixing intensity and impact frequency of the mass in relation to the eddies formed within the off-bottom clearance. The changes were not associated with the reduction in the circulating material load by entrapment into the off-bottom clearance. In the melt pelletization process, the quality of product was higher if the clearance was kept to a minimum. The off-bottom clearance was best measured at the beginning of each pelletization run because the PTFE floor of the mixer was prone to erosion.

Drug Compounding↗
PubMed1999

Effects of physical properties of PEG 6000 on pellets produced by melt pelletization.

This study examined the effects of polyethylene glycol (PEG) binders of different physical forms and from different commercial sources on size and size distribution of pellets produced. The meltable binders used were PEG 6000 in the form of flakes, and coarse and fine powders, and melt pelletization using lactose 450 M was carried out in an 8-liter high-shear mixer. Binder particle size, molecular weight, tack, and viscosity were determined. The results showed that the size and size distribution of the pellets obtained could not be explained by the binder particle size. The size and size distribution of the pellets were related to the tack and viscosity of the molten binders. PEGs used were labeled as the same nominal molecular weight grade, although their determined molecular weights could be quite different. Differences in tack and viscosity of the molten binders were associated with determined molecular weight of the binders. The melt pelletization process is sensitive to tack and viscosity of the molten binders. When different PEG brands of the same nominal molecular weight or different batches of the same brand are used in melt pelletization, it is important to characterize the tack and viscosity of the binders used. The effects of the physical form of binders on the pellet quality appear to be less important when compared to the influences of tack and viscosity of the molten binder.

Drug Compounding↗
PubMed1999

Mixed polymer coating for modified release from coated spheroids.

Modified-release drug spheroids coated with an aqueous mixture of high-viscosity hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were formulated. The preparation of core drug spheroids and the coating procedures were performed using the rotary processor and a bottom-spray fluidized bed, respectively. Dissolution studies indicated that incorporation of suitable additives, such as poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) 400 (PEG) improved the flexibility and integrity of the coat layer by retarding the drug release. An increase in coating levels applied generally retarded the release rate of the drug. However, the ratio of HPMC to NaCMC in the mixed, plasticized polymeric coat played a more dominant role in determining the dissolution T50% values. The optimal ratio of HPMC to NaCMC for prolonged drug release was found to be 3:1, whereas an increase in the amount of NaCMC in the mixed polymer coat only increased drug release. The synergistic viscosity effect of HPMC and NaCMC in retarding drug release rate was greater in distilled water than in dissolution media of pH 1 and 7.2. Cross-sectional view of the scanning electron micrograph showed that all of the coated spheroids exhibited a well-fused, continuous, and distinct layer of coating film. The drug release kinetics followed a biexponential first-order kinetic model.

Carboxymethylcellulose Sodium↗
PubMed1999

Mechanism of pellet coat rupture and its effect on drug release.

In the formation of a coated controlled release preparation with functional coat layers, hydroxypropyl-methylcellulose was used to form a diffusion layer which swelled immediately upon wetting. Eudragit RS30D was used to form the outer retention layer. The rupture of pellet coat occurred when the Eudragit RS30D was unable to withstand the expansion in volume due to the influx of water and swelling of the hydroxypropylmethylcellulose diffusion layer. The sucrose core was able to contribute an osmotic effect. The hydrostatic pressure built up within the pellet can cause the pellet coat to rupture. Sodium chloride deposited in the diffusion coat was able to delay the bursting of the pellet coat. This was due to the competition for the imbibed water between sodium chloride and hydroxypropylmethylcellulose. The rupture of the pellet coat did not result in a total failure of the controlled drug delivery mechanism. Similar drug release rates were obtained irrespective whether there was a puncture in the pellet coat or not. Pressure built-up in the region away from the puncture pushed the core material towards the point of puncture and sealed the puncture point. In addition, the swelling of polymer around the point of rupture ensured continuity in the drug diffusion barrier.

Chlorpheniramine↗
PubMed1988

The effect of moisture on the cohesive properties of microcrystalline celluloses.

A comparative evaluation of two microcrystalline celluloses, Avicel PH101 and Emcocel, revealed some differences in their cohesive properties at different moisture contents. A new method of sandwich rheometry was used to evaluate the cohesive properties of different powder masses. The force required to cause shear failure of a rough-surfaced blade in a powder bed was recorded. Avicel PH101 was found to be more cohesive than Emococel at moisture contents less than 30 wt%, whereas at higher moisture contents the cohesive behaviour was comparable.

Cellulose↗