Tribo Electrification And Adhesion Properties Biology Essay

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Numerous types of pharmaceutical excipients are employed in formulations to improve or modulate tablet characteristics. Among them methylcellulose and hypromellose (HPMC) are the ones that are more frequently used to control drug release from hydrophilic matrices ().The different grades of MC and HPMC may vary in viscosity (molecular size), substitution ratio and particle size. MC and HPMC are identified by codes. For instance, in those manufactured by the Dow Chemical Company, the first part is a letter (A, E, F or K) that relates to the degree of substitution. The K grades (hypromellose 2208) have a methoxy substitution of 19- 24% and a hydroxypropyl substitution of 7-12%. F grades (hypromellose 2906) have a methoxy substitution of 27-30% and a hydroxypropyl substitution of 4.0- 7.5%. E grades (hypromellose 2910) have a methoxy substitution of 28-30% and a hydroxypropyl substitution of 7-12%. A grades (Methyl cellulose) have only methoxy substitution of 27-32% (Dow Commercial Information 2002). This first letter is followed by an indication of the viscosity of their aqueous 2% w/w gels (in centi Poises) at 200C, with a multiplier of 100 (denoted by the letter C) or 1000 (denoted by the letter M). A final suffix identifies the grade of the material, such as premium (P), low viscosity (LV), controlled release (CR), granular (G), surface treated (S) or food grade (FG). The availability of different grades of MC and HPMC have a significant effect on tablet properties ().

In spite of extensive research on MC and HPMC powders and matrices, the tribo-electrification and adhesion characteristics of these polymers and their subsequent impact on high and low tribo-electric charged drugs are not completely understood. Tribo-electrification is a phenomenon which is generated when two electrically charge moieties came in contact with each other and separated. Most of pharmaceutical materials are electrically insulators. When powder particles are came in contact they developed a charge which gave rise to an electrical field around their surface area. This charging process can be due to electron transfer, where the charging occurs by a flow of electrons (Chowdry and Westgate 1974) ion transfer, where ions are exchanged by diffusion (Diaz and Fenzel-Alexander 1993) or due to material transfer, where material is rubbed off one contacting body and adheres on the other one (Tanoue, Ema et al. 1999). Normally the charging process is a combination of these three proceedings. To describe the charging processes of pharmaceutical powders usually the electron transfer model is used because it provides a good understandable description of a charging process. In pharmaceutical industry during powder processing and handling procedures like milling, transport, mixing and sieving the powder particles engendered tribo-electric charge due to frequent abrasion and collision between the particles and the surface wall of the processing apparatus. It usually a nuisance which may cause problems like dust explosions, power particle adhesion during manufacturing and alteration in the dose uniformity of dosage form like tablets. The charged powder particles repel/attract and stick to the wall of the equipment depending on the magnitude and polarity ( negative or positive) of the tribo-electric charge, which may lead to agglomeration or segregation during powder handling.

In the current study firstly the tribo-electrification and adhesion properties of pure MC and HPMC were carried out and systematically the effect of polymer particle size, hyroxypropyl (HPO) / methoxy (Meo) substitution ratio and viscosity on tribo-electric charge and powder particle adhesion with the wall of processing equipment was analysed.

Flurbiprofen belonging to the non-steroidal anti-inflammatory (NSAIDs) class which is highly tribo-electrically charged and had poor adhesion, flow and compaction properties, while theophylline (bronchodilator) comparatively has low charge and good adhesion, flow and compaction properties. The adhesion and tribo-electric charging characteristics of both the model drugs were fully characterised. Furthermore powder mixtures having different proportionality of MC and HPMC with these two drugs were formulated to fully understand how the drug to polymer ratio, hyroxypropyl (HPO) / methoxy (Meo) substitution ratio, particle size and viscosity has an impact on the charging and powder particle adhesion. The impact of tribo-electrification on powder particle adhesion was also investigated. Two way ANOVA was applied on all the findings to check the significance level of all the contributing factors.

Materials and methods

2.1-Materials

Flurbiprofen and theophylline was purchased from Aesica Pharmaceutical Ltd, Cramlington, UK and Tokyo Chemical Industry Ltd, Oxford, UK, respectively. Methylcellulose, MC, ( Methocel® A4M Premium) and hypromellose, HPMC, (Methocel® F4M Premium, Methocel® E4M Premium, Methocel® K4M Premium, Methocel® K15M Premium and Methocel® K100M Premium) was provided by Colorcon Ltd, Dartford, Uk as a kind gift samples. The samples of MC (Methocel® A4M Premium) and HPMC (Methocel® F4M Premium, Methocel® E4M Premium, Methocel® K4M Premium) was varied in both hydroxypropyl (HPO)/ methoxy (Meo) and total substitution ratios but essentially almost have the same viscosity as illustrated in table 1. Methocel® K4M Premium, Methocel® K15M Premium and Methocel® K100M Premium have minor differences in HPO/Meo and total substitution ratios but significantly have different viscosities as described in table 2.

Material

Methoxy (Meo)

(% w/w) a

Hydroxypropyl (HPO) (% w/w) a

HPO/Meo ratio

Total degree of substitution

(% w/w)

Viscosity (cps) a

Batch number a

Methocel® A4M Premium

30

0

0

30

4878

VI14012N03

Methocel® F4M Premium

28.1

6.7

0.238

34.8

4031

WH110212N11

Methocel® E4M Premium

29

8.3

0.2862

37.3

3919

XH13012N11

Methocel® K4M Premium

22.3

8.5

0.3811

31.3

4351

ZG31012N02

a Values obtained from the manufacturer.

Material

Methoxy (Meo)

(% w/w) a

Hydroxypropyl (HPO) (% w/w) a

HPO/Meo ratio

Total degree of substitution

(% w/w)

Viscosity (cps) a

Batch number a

Methocel® K4M Premium

22.3

8.5

0.3811

30.8

4351

ZG31012N02

Methocel® K15M Premium

22.3

9.5

0.4260

31.8

17129

ZC30012N03

Methocel® K100M Premium

22.5

10.2

0.4533

32.7

79279

ZG2012N01

a Values obtained from the manufacturer.

2.2-Methods

2.2.1- Drugs, MC and HPMC fractionation

30g samples of MC, HPMC, Flurbiprofen and theophylline powders were sieved. Two sieve stack, firstly, comprising 250 µm, 150 µm and 75 µm and, secondly, 75 µm and 38 µm respectively for polymers and drugs was assembled in decreasing aperture size from top to bottom. The sieves were agitated using an automatic sieve shaker (Endecotts Test Sieves Ltd. ) for 20 minutes. The weight of each sieve fraction was determined and the sieves were agitated for a further 5 minutes and the weight fractions were redetermined. This procedure was repeated until the weight difference between the shakings was less than 5%. All the sieve fractions were stored in a amber glass bottle at room temperature.

2.3- Particle surface morphology

The particle surface morphology of polymers and drugs was determined by using scaning electron microscope (SEM). The powder samples were sputter-coated with gold for 60 s using (..................) sputter coater. All the samples were analysed by using (..............) and images were obtained under vacuum using an accelerated voltage of 20 kv.

2.4- Preparation of powder mixtures

The powder mixtures of flurbiprofen and theophylline having particle size 38-75 µm were made with MC (Methocel® A4M Premium) and HPMC (Methocel® F4M Premium, Methocel® E4M Premium, Methocel® K4M Premium, Methocel® K15M Premium and Methocel® k1004M Premium) having particle size < 150 µm and 150-250 µm at a fixed polymer to drug ratio of 0.5 %, 1 %, 2.5 %, 5%, 10% and 15 %. The samples were mixed for 20 minutes by using a Bespoke Tumble Mixer, powered by Parvalus motors, Uk.

2.5- Content homogeneity of powder mixtures

To ensure an accurate mixing a random sample of 10 mg (n=3) was taken from each powder mixture and dissolved in 100ml of deionized water and analysed by using UV-Vis Spectrophotometer at wavelength (ÊŽ) of 247 nm and 272 nm for flurbiprofen and theophylline respectively. The drug content was calculated by using the equation which was obtained from standard calibration curves of respective drugs.

2.6- Tribo-electrification

Charge to mass ratio (Q/M) is an important and critical parameter which has to properly analysed in order to understand and predict the behaviour of electrostatically charged particles. Charge to mass ratio (Q/M) of pure drugs, MC, HPMC and their respective powder mixtures were determined by using a tribo-electric device based on a shaking concept, as described by Supuk and co-workers. A sample of approximately 0.1 g (accurately weighed) of powder was placed inside a cylindrical container which was shaken in a horizontal direction by using MW 4000 shaking device . The sample material was shaken for 5 minutes at a vibration frequency of 20. A fresh sample was used for each test at each time point. The shaking container had a volume of 10 ml and was made out of stainless steel. The charged powder particles then poured in a Faraday up connected to an electrometer A Faraday cup consists of two concentric cups made up of a conducting material. The outer cup is slightly larger and it is grounded to act as an electrical shield and it is covered by a heavy lid. Both are very important to prevent the effect of any extraneous electric fields. The inner cup is directly attached to an electrometer for charge measurement and can be removed to measure the weight of the sample poured. The two cups are separated from each other by insulator (PTFE). As a charged sample is loaded into the inner faraday cup, the electrical field present around the surface of particle redistributed the electron on the wall of inner faraday cup by either attracting or repulsing the electrons. That induced equal but opposite charge on the wall of inner faraday cup. The induced charge is then measure by using electrometer ( Keithley Model 6514), providing the net charge on the object. The resolution of the charge measurement is in nano-coulombs (nC). The charge to mass ratio (Q/M)

After measuring the charge, the samples were weighed and the total charge per unit mass, that is, the specific charge, was calculated.

In order to produce reliable data, each tribo-electric charging test was repeated three times. The shaking container was cleaned to remove any deposits, impurities and surface charge that may have been present on the surface from a previous test. Remaining material and associated charge was removed between each test by washing the surface with isopropyl alcohol. This material was allowed to evaporate before further tests were carried out. All the tribo-electrification experiments were carried out at ambient temperature ( 18-24 0C) and humidity (RH 36-44 %).

2.7- Particle adhesion

During the tribo-electric charging tests, particles adhered to the inner surfaces of the shaking container. This was due to the fact that a sufficiently large force may be formed, due to tribo-electrification, to cause particle adhesion and agglomeration. Particle adherence was calculated from mass difference by deducting the final amount recovered (post shaking and tapping) from the initial amount of sample loaded into the shaking vessel (typically 0.1 g).

2.8- Statistical analysis

Two way analysis of variance (ANOVA) was applied by using SPSS 20 to

Results and discussion

3.1- Powder particle morphology and content uniformity of powdered mixtures

3.2- Tribo-electrification and adhesion properties of MC and HPMC

3.2.1- Effect of particle size

3.2.2- Effect of substitution ratio

3.2.3- Effect of molecular size

3.3- Tribo-electric charge and adhesion properties of flurbiprofen and theophylline

3.4- Tribo-electrification and adhesion properties of formulated powder mixtures

3.4.1- Effect of polymer concentration

3.4.2- Effect of polymer substitution ratio

3.4.3- Effect of Viscosity

3.4.4- Effect of particle size

3.5- Influence of tribo-electric charge on adhesion properties of powder mixtures.

Conclusion

Acknowledgements

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