Cuencas Sedimentarias de Petróleo en Colombia

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Figure 4.1 Ampoule microcalorimetry response for the as received spray-dried lactose

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Figure 4.1 shows a typical microcalorimetry response for the as received spray-dried lactose. The analysis of 100% amorphous spray-dried lactose has been covered in the literature (Briggner et al, 1994, Buckton and Darcy, 1995, and Chidavaenzi et al, 1997). The amorphous lactose recrystallises in a cooperative manner, whereby the entire powder bed becomes saturated with water vapour before crystallisation commences. This could also apply to the spray-dried lactose studied here since despite the sample containing only a small amount of amorphous lactose, the same sharp peak is seen in Figure 4.1 followed by a rapid decline to the baseline, as for the 100% amorphous lactose in the literature.

The area under the curve (AUC) for a plot of power (dQ/dt) against time (t) gives the heat associated with the process being measured. In the case of recrystallisation of 100% amorphous spray-dried lactose, a value of 48 mJ/mg has been found to correspond to recrystallisation of all of the amorphous lactose in the sample (Darcy,

1998). The magnitude of the recrystallisation has been shown by Briggner et al (1994) to be directly proportional to the degree of crystalline material in the sample. The amount of amorphous material in a sample can then be calculated by the ratio of the area under the crystallisation peak for the test sample to that of a 100% amorphous sample. Briggner et al (1994) state that for this to apply the powder loading must be identical, or is normalised. For the experiments carried out for spray-dried lactose, the areas under the curve are expressed in mJ/mg of the total weight of the sample.

For the spray-dried lactose used in this investigation, the area under the curve was 5.2 mJ/mg +/- 0.4 (n = 3). The area under the curve for 100% amorphous spray-dried lactose is 48 mJ/mg (Darcy, 1998). The percentage amorphous content of the spray- dried lactose was then calculated as 10.8 %.

Figure 4.1 shows a broad response prior to the recrystallisation event. This initial response has been observed in studies of 100% amorphous spray-dried lactose. It was previously thought that this peak was due to water sorption (Sebhatu et al, 1994, and Briggner et al, 1994). However, recent studies have shown that the initial peak is also due to collapse of the amorphous lactose (Buckton and Darcy, 1996). The studies of 100% amorphous lactose have shown that the initial collapse peak has been a separate peak to the main recrystallisation peak (Buckton et al, 1995, and Sebhatu et al, 1994a) with the curve returning to the baseline prior to the main recrystallisation peak. Figure 4.1 shows that the initial peak does not return to the baseline prior to the recrystallisation peak, and instead has a small quasi-plateau region before developing into the main recrystallisation peak. This has previously been observed by Briggner et al (1994) when lactose samples that were fluid energy milled were analysed using isothermal microcalorimetry. The microcalorimetry outputs consisted of a quasi-plateau region prior to the main reciystallisation peak. The percentage of amorphous material induced in the samples as a result of the fluid energy milling was in the range of 7.3 to

14.5% depending on the pressures used.

The quasi-plateau peak observed for the spray-dried lactose sample and the fluid energy milled samples both consist of small amounts of amorphous material (typically 10-12%) suggesting that the absence of the collapse peak returning to the baseline prior to the main recrystallisation peak may be due to this. It may be that since the amount of amorphous material is small, saturation of the amorphous portion of the sample with water vapour vnW take place faster than for a sample with 100% amorphous lactose

material. This would allow recrystallisation to take place faster, perhaps then resulting in the collapse and recrystallisation peaks joining together.

4.3.2 Thermogravimetric Analysis (TGA) investigation

102 100 _ 96 90 0 20 40 60 80 100 120 140 160 180 200 220 240 Tem perature (°C)

Figure 4.2 Typical TGA curve fo r as received spray-dried lactose up to 230^C at 10^ C/minute

Figure 4.2 shows a typical TGA trace for as received spray-dried lactose. It shows the lactose, which has been shown to consist of 10.8% amorphous lactose, loses 1.2% +/- 0.01 (n = 3) water below lOO^C and 4.5% +/- 0.01 (n = 3) crystal water between lOO^^C and 150°C. The percentage a-lactose monohydrate in the sample can be quantitatively obtained from the TGA data knowing that the theoretical weight loss of hydrate water for 100% a-lactose monohydrate is 5%. The percentage of a-lactose monohydrate in the spray-dried sample amounts to 90.0% +/- 0.2 (n = 3). This corresponds with the 10.8% amorphous lactose present, determined using isothermal microcalorimetry. The TGA results indicate that the remaining ca. 90% consists of a-lactose monohydrate.

4.3.3 Differential Scanning Calorimetry (DSC) investigation

Figure 4.3 shows three DSC seans for as received spray-dried lactose. It shows a dehydration peak at 142.0®C +/- 0.4 (n = 3) and a melting peak at 220.2°C +/- 0.5 (n = 3). The endothermie peak at 142°C can be attributed to the loss of hydrate water. The melting endotherm at 220°C can be attributed to the melting of a-lactose. The DSC trace does not show any recrystallisation exotherms as would have been expected given that the sample has been shown to consist of 10.8% amorphous lactose by isothermal microcalorimtery. However, this may be due to the lower sensitivity of the DSC towards small amounts of amorphous material (Angberg, 1995). In contrast, isothermal microcalorimetry has already been shown to be able to detect small amounts of amorphous lactose (Buckton et al, 1995).

The DSC trace for spray-dried lactose shows the absence of a p-lactose melting peak at around 230°C, suggesting that no crystalline p-lactose is present. The absence of a p- lactose melting response does not prove complete absence of crystalline P-lactose since it may be below the detection limits of the instrument.

8 0 .0 - Peak 141.86 *C AH 10 1 .7 3 J /g 7 0 .0 - Peak 2 1 9 .5 8 *C AH 143 .7 9 J /g

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Figure 4.3 DSC traces for as received spray-dried lactose showing a dehydration peak at 142°C and a melting peak at 220°C

4.3.4 Conclusion

The above analysis of the as received spray-dried lactose shows that it consists of ca. 90% a-lactose monohydrate and ca. 10% amorphous lactose.

4.4 INVESTIGATION OF FLUID-BED DRYING OF SPRAY-DRIED LACTOSE