Effects of Excipients on Hydrate Formation in Wet Masses Containing Theophylline

Airaksinen, Sari; Luukkonen, Pirjo; Jørgensen, Anna Cecilia; Karjalainen, Milja; Rantanen, Jukka; Yliruusi, Jouko

doi:10.1002/jps.10328

Cited by 66 publications

(42 citation statements)

References 30 publications

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“…This product had to be reconstituted by the patient, but the dissolution of the capsules failed. Airaksinen et al [26] Gewijzigde veldcode and Wikström et al [27] studied the conversion of anhydrous theophylline into theophylline monohydrate using a planetary mixer and a high-shear mixer granulator, respectively.…”

Section: Gewijzigde Veldcodementioning

confidence: 99%

Real-time assessment of critical quality attributes of a continuous granulation process

Fonteyne

Vercruysse

Díaz

et al. 2011

Pharmaceutical Development and Technology

104

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There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline -lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

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Section: Gewijzigde Veldcodementioning

confidence: 99%

Real-time assessment of critical quality attributes of a continuous granulation process

Fonteyne

Vercruysse

Díaz

et al. 2011

Pharmaceutical Development and Technology

104

View full text Add to dashboard Cite

show abstract

“…[57][58][59][60] The effects of different excipients on these hydration and dehydration processes have also been evaluated by different authors. 28,[61][62][63][64] Unfortunately, however, these studies not only use different techniques (ranging from thermogravimetric methods to spectroscopic tools), but they also consider very different experimental conditions (temperature, humidity, sample handling and preparation), known to have a great influence on both pseudopolymorphic transformations. This fact is probably the origin of some of the discrepancies found in the literature.…”

Section: Introductionmentioning

confidence: 99%

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

Amado

Nolasco

Ribeiro‐Claro

2007

Journal of Pharmaceutical Sciences

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Theophylline is known to undergo vapor phase induced hydrate-anhydrate pseudopolymorphic transformations, which can affect its bioavailability. In this work, the kinetics of the pseudopolymorphic transitions of theophylline crystals in different storage conditions is studied using a vibrational spectroscopic technique. While the hydration is a single-step process with a half-life time of ca. 5 h, the dehydration occurs through a two-step mechanism. In addition, the phase stability of hydrate-anhydrate systems in different relative humidity (RH) conditions was probed. The critical RH for anhydrous teophylline was found to be at ca. 79%, while the critical RH for dehydration is ca. 30%. ß

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“…16,25,39 Since the amount of drug was relatively low, it was difficult to detect the hydrate formation from the Raman spectra measured at-line during processing. Previously, it had been shown that theophylline was a good Raman scatterer.…”

Section: The Theophylline Formulationmentioning

confidence: 99%

“…The polymorphic change of theophylline during wet granulation has also been discussed by R€ as€ anen et al 15 and Morris et al 3 The choice of excipients has an impact on hydrate formation of theophylline in wet masses. 16 Rodr ıguez-Hornedo et al 17 have investigated the kinetics of the anhydrous-to-hydrate transformation of theophylline. In addition to theophylline, nitrofurantoin possesses a tendency for phase transitions in different humidity conditions.…”

Section: Introductionmentioning

confidence: 99%

Pellet manufacturing by extrusion-spheronization using process analytical technology

et al. 2005

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The aim of this study was to investigate the phase transitions occurring in nitrofurantoin and theophylline formulations during pelletization by extrusion-spheronization. An at-line process analytical technology (PAT) approach was used to increase the understanding of the solid-state behavior of the active pharmaceutical ingredients (APIs) during pelletization. Raman spectroscopy, near-infrared (NIR) spectroscopy, and X-ray powder diffraction (XRPD) were used in the characterization of polymorphic changes during the process. Samples were collected at the end of each processing stage (blending, granulation, extrusion, spheronization, and drying). Batches were dried at 3 temperature levels (60°C, 100°C, and 135°C). Water induced a hydrate formation in both model formulations during processing. NIR spectroscopy gave valuable real-time data about the state of water in the system, but it was not able to detect the hydrate formation in the theophylline and nitrofurantoin formulations during the granulation, extrusion, and spheronization stages because of the saturation of the water signal. Raman and XRPD measurement results confirmed the expected pseudopolymorphic changes of the APIs in the wet process stages. The relatively low level of Raman signal with the theophylline formulation complicated the interpretation. The drying temperature had a significant effect on dehydration. For a channel hydrate (theophylline), dehydration occurred at lower drying temperatures. In the case of isolated site hydrate (nitrofurantoin), dehydration was observed at higher temperatures. To reach an understanding of the process and to find the critical process parameters, the use of complementary analytical techniques are absolutely necessary when signals from APIs and different excipients overlap each other.

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Effects of Excipients on Hydrate Formation in Wet Masses Containing Theophylline

Cited by 66 publications

References 30 publications

Real-time assessment of critical quality attributes of a continuous granulation process

Real-time assessment of critical quality attributes of a continuous granulation process

Probing Pseudopolymorphic Transitions in Pharmaceutical Solids using Raman Spectroscopy: Hydration and Dehydration of Theophylline

Pellet manufacturing by extrusion-spheronization using process analytical technology

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