Use of Glancing Angle X-Ray Powder Diffractometry to Depth-Profile Phase Transformations During Dissolution of Indomethacin and Theophylline Tablets

Debnath, Smita; Predecki, Paul; Suryanarayanan, Raj

doi:10.1023/b:pham.0000012163.89163.f8

Cited by 46 publications

(46 citation statements)

References 13 publications

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“…Therefore, glancing angle XRD, a technique described elsewhere, was used to quantify the anhydrate → hydrate transition as a function of tablet depth. 16 On exposure to the dissolution medium for ~30 seconds, there was ~78% and 90% conversion to theophylline monohydrate at the surface of the compacts prepared using the unprocessed and processed drug, respectively ( Figure 2). Because of its lower crystallinity, the processed anhydrate (Case 3) dissolved at a faster rate, resulting in more rapid supersaturation at the compact surface followed by a higher rate of hydrate crystallization.…”

Section: Effect Of Processing On Drug Dissolutionmentioning

confidence: 99%

Influence of processing-induced phase transformations on the dissolution of theophylline tablets

Debnath

Suryanarayanan

2004

AAPS PharmSciTech

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INTRODUCTIONThe object of this investigation was to evaluate the influence of (1) processing-induced decrease in drug crystallinity and (2) phase transformations during dissolution, on the performance of theophylline tablet formulations. Anhydrous theophylline underwent multiple transformations (anhydrate → hydrate → anhydrate) during processing. Although the crystallinity of the anhydrate obtained finally was lower than that of the unprocessed drug, it dissolved at a slower rate. This decrease in dissolution rate was attributed to the accelerated anhydrate to hydrate transformation during the dissolution run. Water vapor sorption studies proved to be a good predictor of powder dissolution behavior. While a decrease in crystallinity was brought about either by milling or by granulation, the effect on tablet dissolution was pronounced only in the latter. Tablet formulations prepared from the granules exhibited higher hardness, longer disintegration time, and slower dissolution than those containing the milled drug. The granules underwent plastic deformation during compression resulting in harder tablets, with delayed disintegration. The high hardness coupled with rapid anhydrate → hydrate transformation during dissolution resulted in the formation of a hydrate layer on the tablet surface, which further delayed tablet disintegration and, consequently, dissolution. Phase transformations during processing and, more importantly, during dissolution influenced the observed dissolution rates. Product performance was a complex function of the physical state of the active and the processing conditions.The physicochemical properties of pharmaceuticals, including solubility and dissolution rate, can be influenced by the degree of crystallinity, solvation state, and crystal form. At room temperature, the anhydrate forms of ampicillin, theophylline, and glutethimide have a higher dissolution rate than their corresponding hydrates. 1 This difference in dissolution rate can be attributed to the difference in the free energy of hydration.1 Similarly, metastable forms, because of their higher free energy, are expected to dissolve more rapidly than their corresponding stable forms. This effect was observed with the metastable polymorphs of acetazolamide, carbamazepine, and indomethacin.2 However, this free energy difference between the stable and metastable forms can also provide the driving force for metastable → stable transformation in the dissolution medium. As a result, the observed difference in dissolution rate can be much lower than the predicted values. 3Although the physical form of a drug substance is carefully selected for dosage form manufacture, the processing conditions will determine the solid state of the drug in the final product. During tablet manufacture, processing steps may include milling, granulation, drying, and compression. Particle size as well as degree of crystallinity can be profoundly affected by milling as has been observed in case of griseofulvin. 4 The use of a binder solution for wet gra...

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Section: Effect Of Processing On Drug Dissolutionmentioning

confidence: 99%

Influence of processing-induced phase transformations on the dissolution of theophylline tablets

Debnath

Suryanarayanan

2004

AAPS PharmSciTech

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“…GAXRD makes pos-sible the use of X-rays for the characterization of surfaces, buried interfaces, and ultra thin films. By means of this technique, valuable information can be obtained regarding the thickness and phase crystallography of the sample [1][2][3], the change of its composition with depth [4], and its microstructure (stress, preferred orientation, etc.) [5].…”

Section: Introductionmentioning

confidence: 99%

Characterization of Thin Films by Low Incidence X-Ray Diffraction

Bouroushian¹,

Kosanovic²

2012

CSTA

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Glancing Angle X-ray Diffraction (GAXRD) is introduced as a direct, non-destructive, surface-sensitive technique for analysis of thin films. The method was applied to polycrystalline thin films (namely, titanium oxide, zinc selenide, cadmium selenide and combinations thereof) obtained by electrochemical growth, in order to determine the composition of ultra-thin surface layers, to estimate film thickness, and perform depth profiling of multilayered heterostructures. The experimental data are treated on the basis of a simple absorption-diffraction model involving the glancing angle of X-ray incidence.

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“…X-ray powder diffraction (XRPD) has been applied to measuring phase transformations on tablet surfaces during dissolution, 15 but there are major challenges, for example, difficulties in the in situ arrangements and high costs. Raman spectroscopy has characteristics that make it suitable for solid phase analysis during dissolution.…”

Section: Introductionmentioning

confidence: 99%

In Situ Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

Aaltonen

Heinänen

Peltonen

et al. 2006

Journal of Pharmaceutical Sciences

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Use of Glancing Angle X-Ray Powder Diffractometry to Depth-Profile Phase Transformations During Dissolution of Indomethacin and Theophylline Tablets

Cited by 46 publications

References 13 publications

Influence of processing-induced phase transformations on the dissolution of theophylline tablets

Influence of processing-induced phase transformations on the dissolution of theophylline tablets

Characterization of Thin Films by Low Incidence X-Ray Diffraction

In Situ Measurement of Solvent-Mediated Phase Transformations During Dissolution Testing

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