Experimental Investigation of Stretch Blow Molding, Part 2: Analysis of Process Variables, Blowing Kinematics, and Bottle Properties

The work presented in this paper takes advantage of newly developed instrumentation suitable for in process monitoring of an industrial stretch blow molding machine. The instrumentation provides blowing pressure and stretch rod force histories along with the kinematics of polymer contact with the mould wall. A Design of Experiments pattern was used to qualitatively relate machine inputs with these process parameters and the thickness distribution of stretch blow molded PET (polyethylene terephtalate) bottles. Material slippage at the mold wall and thickness distribution is also discussed in relation to machine inputs. The key process indicators defined have great potential for use in a closed loop process control system and for validation of process simulations.

Contribution of process variables to the entrapment efficiency of propranolol hydrochloride within ethylcellulose microspheres prepared by the solvent evaporation method as evaluated using a factorial design

The effects of the process variables, pH of aqueous phase, rate of addition of organic, polymeric, drug-containing phase to aqueous phase, organic:aqueous phase volume ratio and aqueous phase temperature on the entrapment of propranolol hydrochloride in ethylcellulose (N4) microspheres prepared by the solvent evaporation method were examined using a factorial design. The observed range of drug entrapment was 1.43 +/- 0.02%w/w (pH 6, 25 degrees C, phase volume ratio 1:10, fast rate of addition) to 16.63 +/- 0.92%w/w (pH 9, 33 degrees C, phase volume ratio 1:10, slow rate of addition) which corresponded to mean entrapment efficiencies of 2.86 and 33.26, respectively. Increased pH, increased temperature and decreased rate of addition significantly enhanced entrapment efficiency. However, organic:aqueous phase volume ratio did not significantly affect drug entrapment. Statistical interactions were observed between pH and rate of addition, pH and temperature, and temperature and rate of addition. The observed interactions involving pH are suggested to be due to the abilities of increased temperature and slow rate of addition to sufficiently enhance the solubility of dichloromethane in the aqueous phase, which at pH 9, but not pH 6, allows partial polymer precipitation prior to drug partitioning into the aqueous phase. The interaction between temperature and rate of addition is due to the relative lack of effect of increased temperature on drug entrapment following slow rate of addition of the organic phase. In comparison to the effects of pH on drug entrapment, the contributions of the other physical factors examined were limited.

Investigation of influence of process variables on mechanical strength, size and homogeneity of pharmaceutical granules produced by fluidised hot melt granulation

The overall aim of the project was to study the influence of process variables on the distribution of a model active pharmaceutical ingredient (API) during fluidised melt granulation of pharmaceutical granules with a view of optimising product characteristics. Granules were produced using common pharmaceutical excipients; lactose monohydrate using poly ethylene glycol (PEG1500) as a meltable binder. Methylene blue was used as a model API. Empirical models relating the process variables to the granules properties such as granule mean size, product homogeneity and granule strength were developed using the design of experiment approach. Fluidising air velocity and fluidising air temperature were shown to strongly influence the product properties. Optimisation studies showed that strong granules with homogeneous distribution of the active ingredient can be produced at high fluidising air velocity and at high fluidising air temperatures.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. © 2012 Elsevier B.V. All rights reserved.

AN INVESTIGATION OF THE EFFECTS OF SOME PROCESS VARIABLES ON THE MICROENCAPSULATION OF PROPRANOLOL HYDROCHLORIDE BY THE SOLVENT EVAPORATION METHOD

The effects of four process factors: pH, emulsifier (gelatin) concentration, mixing and batch, on the % w/w entrapment of propranolol hydrochloride in ethylcellulose microcapsules prepared by the solvent evaporation process were examined using a factorial design. In this design the minimum % w/w entrapments of propranolol hydrochloride were observed whenever the external aqueous phase contained 1.5% w/v gelatin at pH 6.0 (0.71-0.91% w/w) whereas maximum entrapments occurred whenever the external aqueous phase was composed of 0.5% w/v gelatin at pH 9.0,(8.9-9.1% w/w). The theoretical maximum loading was 50% w/w. Statistical evaluation of the results by analysis of variance showed that emulsifer (gelatin) concentration and pH, but not mixing and batch significantly affected entrapment. An interaction between pH and gelatin concentration was observed in the factorial design which was accredited to the greater effect of gelatin concentration on % w/w entrapment at pH 9.0 than at pH 6.0. Maximum theoretical entrapment was achieved by increasing the pH of the external phase to 12.0. Marked increases in drug entrapment were observed whenever the pH of the external phase exceeded the pK(2) of propranolol hydrochloride. It was concluded that pH, and hence ionisation, was the greatest determinant of entrapment of propranolol hydrochloride into microcapsules prepared by the solvent evaporation process.

Neural modelling, control and optimisation of an industrial grinding process

This paper describes the development of neural model-based control strategies for the optimisation of an industrial aluminium substrate disk grinding process. The grindstone removal rate varies considerably over a stone life and is a highly nonlinear function of process variables. Using historical grindstone performance data, a NARX-based neural network model is developed. This model is then used to implement a direct inverse controller and an internal model controller based on the process settings and previous removal rates. Preliminary plant investigations show that thickness defects can be reduced by 50% or more, compared to other schemes employed. (c) 2004 Elsevier Ltd. All rights reserved.

Influence of process parameters on fluidised hot-melt granulation and tablet pressing of pharmaceutical powders

This study investigates the influence of process parameters on the fluidised hot melt granulation of lactose and PEG 6000, and the subsequent tablet pressing of the granules. Granulation experiments were performed to assess the effect of granulation time and binder content of the feed on the resulting granule properties such as mass mean granule size, size distribution, granule fracture stress, and granule porosity. These data were correlated using the granule growth regime model. It was found that the dominant granule growth mechanisms in this melt granulation system were nucleation followed by steady growth (PEG 10–20% w/w). However, with binder contents greater than 20% w/w, the granulation mechanism moved to the “over-wet massing” regime in which discrete granule formation could not be obtained. The granules produced in the melt fluidised bed process were subsequently pressed into tablets using an industrial tablet press. The physical properties of the tablets: fracture stress, disintegration time and friability were assessed using industry standards. These analyses indicated that particle size and binder content of the initial granules influenced the mechanical properties of the tablets. It was noted that a decrease in initial granule size resulted in an increase in the fracture stress of the tablets formed.