Preparation and Characterization of Meloxicam–Myrj-52 Granules Obtained by Melt Granulation - Pharmaceutical Technology

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Preparation and Characterization of Meloxicam–Myrj-52 Granules Obtained by Melt Granulation
Various manufacturing techniques can improve a drug's solubility, thus increasing its bioavailability. The authors examined whether melt granulation can enhance drug solubility using meloxicam as the drug substance and myrj-52 as the binder.


Pharmaceutical Technology



Figure 4: Differential scanning calorimetry curves of pure meloxicam, myrj-52, StarLac, melt granulation (MG) of meloxicam in myrj-52, physical mixture (PM) of meloxicam in myrj-52, and solid dispersion (SD) of meloxicam in myrj-52.
Differential scanning calorimetry. The thermal properties of the drug, myrj-52, PM, SD, and granules prepared by melt granulation were studied using DSC (see Figure 4). Meloxicam shows a sharp melting endothem at 258.1 C. The exothermic peak after the melting peak may be part of the decomposition peaks also observed by Cantera et al. in tenoxicam (13). Thin-layer chromatography of meloxicam melted at 265 C on an oil bath showed two different bands, which indicate the decomposition of the drug in melt form. The color of drug after melting at 265 C also changed from yellow to reddish brown. Slow, controlled heating of the drug in DSC did not yield two separate peaks for melting and decomposition. DSC of pure myrj-52 showed an endothermic peak at 51 C. The thermogram of pure StarLac showed endothermic peaks at 150 and 215 C for starch and lactose, respectively. The thermogram of physical mixture with myrj-52 showed endothermic peaks at 49.9, 103.9, 216, and 231 C, corresponding to myrj-52, starch, lactose, and meloxicam, respectively. Normalized enthalpics of PM, SD, and MG samples were lower (i.e., 63.8, 77.0, and 61.2 J/g, respectively) compared with pure meloxicam (338.1 J/g).

The shift and breadth of the endothermic peak probably results from the partial reduction in crystallinity, which may be confirmed in PXRD studies.

Powder X-ray diffractometry. The authors performed PXRD analysis to confirm the crystalline nature of meloxicam in the granules. The numerous sharp and intense peaks in the diffractrogram of untreated meloxicam shows that the drug is crystalline.


Figure 5: X-ray diffraction pattern of pure meloxicam, myrj-52, StarLac, melt granulation (MG) of meloxicam in myrj-52, physical mixture (PM) of meloxicam in myrj-52, and solid dispersion (SD) of meloxicam in myrj-52.
PXRD of meloxicam showed characteristic peaks at 13, 14.5, 18.5, and 26. Peaks at 26 were used to compare the PXRD pattern of the drug with those of PM, MG, and SD (see Figure 5). A significant reduction in peak intensities was observed in the PXRD patterns of PM, MG, and SD compared with that of the pure drug. The PXRD pattern of myrj-52 showed two typical peaks in the region of 19.5 and 24. The PXRD patterns of PM, MG, and SD showed all of meloxicam's peaks except for the peak at 26. The disappearance of the peak at 26 in the patterns of PM, SD, and MG might result from an attenuation of the signal in the presence of excipients or preferential orientation.

The traces of PM, MG, and SD are similar to each other. The characteristic peaks of the drug are always present, indicating that meloxicam is crystalline in PM, MG, and SD samples. Therefore, X-ray data confirm that the enhanced dissolution rate of the drug does not result from the transformation of the crystalline form into the amorphous state.


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