Selection of a Second Polymeric Material for Mechanical Strength Evaluation

3.5.1 Assessment of Material Compressibility/Compactihility

The mechanical properties of a second polymeric material were evaluated for comparison with Avicel PHI 02 (Chapter 2, Section 2.1.1) after selection from three materials. The three materials hydroxypropyl cellulose (Klucel), hydroxypropyl methylcellulose (Methocel E4M) and sodium alginate were investigated as received and their details are given in Table 2.1. Compacts of 0.4g and 0.8g approximately were

prepared at two compaction pressures using each material as described in Chapter 2, Section 2.3.1. During die-filling particular attention was given to powder flow and ease of handling whilst after compaction the quality of the tablet was assessed by visual means. The tablets were then weighed and their dimensions were measured to roughly assess the volume reduction properties of the powders. Finally specimens were subjected to diametral testing between hardened steel platens using a commercial testing machine (CT40, Engineering Systems, Nottingham) with a platen speed of Imm/min.

3.5.2 Results

Sodium Alginate possessed good flow properties but did not form compacts at either 50 or 1 SOMPa. On attempting to remove the die contents the ‘compact’ crumbled to powder. Sodium Alginate was therefore considered non-compressible and unsuitable for further investigation.

Methocel E4M possessed acceptable flow properties but exhibited slight adhesiveness. It formed good tablets at both compaction pressures which had a smooth appearance. Upon diametral compression fracture loads of 8.16 and 19.33kg were recorded with a clean central tensile failure.

Klucel was very easy to handle and flowed well. It formed specimens at both compaction pressures with a slightly granular surface. However, upon diametral testing a fracture load could not be obtained as specimens continually deformed under an increasing

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load. Eventually specimens became a cylindrical pipe shape and a small hole appeared in one of the faces of the tablet. This did not appear to be the result of failure but merely occurred as the result of lateral deformation (the only direction remaining in which the specimen could deform).

Methocel E4M was therefore selected for use by default as the use of Klucel would not have enabled the determination of mechanical strength.

Such simple tests as described above could be used to evaluate the potential of a material for use as a binder in a direct compression (DC) matrix formulation. Klucel demonstrated considerable plasticity in these tests and consequently is regularly used as a polymeric matrix in DC formulations.

3.5.3 Determination of Compressive Young s Modulus 3.5.3.1 Introduction

The concept of the Young’s modulus of elasticity was introduced in Chapter 1, Section 1.2.1. The advantages of a compressive determination as opposed to the three- or four-point beam bending method for pharmaceutical materials have been discussed in Chapter 1, Section 1.2.5.5. The compressive Young’s modulus (E) was determined for both Avicel PH 102 and Methocel E4M to allow a preliminary comparison of their mechanical properties using a technique described for cylindrical specimens (Paddon and Wilson, 1976; Kerridge and Newton, 1986; Kerridge 1988).

3.5.3.2 Experimental

Twelve millimetre diameter cylindrical specimens of both materials were prepared over a range of porosities, using an Instron Physical Testing Machine as described in Chapter 2, Section 2.3.1 in conjunction with a specially constructed extra-long die. Specimens were compacted at a rate of 0.5cm/min with five replicates prepared at each porosity. After 14 days storage in sealed plastic bags the specimens were weighed and measured and their porosity was calculated as shown in Section 3 .2.1.1.

The compressive Young’s modulus was determined by straining the specimens between two 25.4mm diameter Manesty Type D3A flat-faced steel punches, used as platens, on the Instron at a crosshead speed of 0.05cm/min. The stress-strain curves for each specimen were recorded using an X-Y plotter with the timebase set to 20s/cm. The

slope of the elastic part of the curve enabled the calculation of the specimen Young’s modulus (Es) using equation 3.4:-

= ( X - M J A (Equation 3.4)

where L is the length of the specimen (m), X is the slope (m/KN), Me is the machine constant, determined by loading the machine without a specimen, (m/KN), and A is the cross-sectional area of the specimen (m^).

Frictional effects at the platens were not corrected for because absolute values of the zero porosity Young’s modulus were not required and the end-eflfects at the platens can never be completely eliminated (Chapter 1, Section 1.2.3.6).

3.S.3.3 Results and Discussion

The results in Figure 3 .8 are presented in the manner described empirically by the

Sprigg’s equation (Sprigg’s, 1961) where a plot of In E, against porosity, P, yields a straight line. The raw data has been used in the linear regression rather than the mean as variation in both E and P is likely. By extrapolating the curve to zero porosity the Young’s modulus of the material (Eo) can be estimated. However, it is important to note that even at zero porosity the value obtained for E still represents a specimen property rather than a true material property although the values obtained for different materials are useful for comparative purposes. Furthermore, the Sprigg’s equation and other relationships describing E as a function of porosity do not completely account for changes in the pore structure which will certainly influence the mechanical properties of the material.

For both Avicel PHI 02 and Methocel E4M linear regression analysis gave a significant linear relationship between Es and porosity yielding the respective equations:

E = 4.093 exp (-15.54P) r = -0.989 (Equation 3.5)

E = 0.576 exp (-5.598P) r = -0.988 (Equation 3.6)

Thus zero porosity moduli of 59.9 and 1.78GPa were obtained for Avicel PH I02 and Methocel E4M respectively. The value obtained for Avicel PH 102 seems erroneously high

Figure 3.8 In as a function of porosity for Avicel PH 102 and Methocel E4M specimens (raw data) (Specimen Young’s Modulus, GPa)

tu 2.0 1.8 1.6 _{Avicel PH 102 (1.25g specimen)} 1.4 1.2 1.0 0.8 0.6 0.4