Evaluation of crystallinity and drug release stability of directly compressed theophylline hydrophilic matrix tablets stored under varied moisture conditions

Adeyeye, Christianah Moji; Rowley, Jennifer; Madu, Donatus; Javadi, Mehran; Sabnis, Shobhan

doi:10.1016/0378-5173(94)00273-8

Cited by 32 publications

(48 citation statements)

References 11 publications

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“…7 The effect of compression pressure on the hydration as well as dissolution behavior of anhydrous theophylline tablets has been investigated. 14,15 During pharmaceutical processing (aqueous wet granulation followed by drying), the stable anhydrous polymorph underwent multiple transformations (stable anhydrate → hydrate → metastable anhydrate). Tablets prepared using the metastable form dissolved at a slower rate than those containing the stable polymorph.…”

Section: Methodsmentioning

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: Methodsmentioning

confidence: 99%

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

Debnath

Suryanarayanan

2004

AAPS PharmSciTech

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“…TPa transformations, and both processes have been studied for the bulk powder 38,[44][45][46][47][48][49][50][51][52][53][54][55][56] and for tablets. [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.…”

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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“…The exception is the methyl group at position N (3) , which does not participate in any hydrogen bond neither in the hydrate structure nor in the anhydrous structure. A characteristic feature of the monohydrated structure is the existence of heaped layers of dimeric structures of TP molecules, related by a centre of symmetry, which are held together by two types of TP···TP interactions, namely N (7) ÀH···O (6) and C (8) ÀH···O (2) (each TP molecule establishing two equivalent interactions of each type, thus acting both as a donor and as an acceptor). In addition, each TP molecule establishes two types of TP···H 2 O interactions (N (9) ···HÀO w and C (1) ÀH···O w ), forming water network channels that cross the different TP molecular layers.…”

Section: Theophyllinementioning

confidence: 99%

“…Based on these results, significant insights are obtained for the structure of caffeine in the anhydrous form (stable at room temperature), for which no X-ray structure has been reported. A possible structure based on C (8) À H···N (9) and C (1,3) ÀH···O intermolecular interactions is suggested. relationship ruling their biochemical effects.…”

Section: Introductionmentioning

confidence: 99%

Computationally‐Assisted Approach to the Vibrational Spectra of Molecular Crystals: Study of Hydrogen‐Bonding and Pseudo‐Polymorphism

2006

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Zwei Stufen, ein Katalysator: Ein Vanadium(V)‐Oxo‐Komplex mit einer dreizähnigen Schiff‐Base als weiterem Ligand katalysiert die Titelreaktion, die racemische (Bis)homoallyl‐α‐hydroxyester in trans‐Tetrahydropyrane (THPs) oder cis‐Tetrahydrofurane (THFs) überführt. Auf diese Art lassen sich cyclische Ether effizient asymmetrisch synthetisieren, wie mit der ersten enantioselektiven Synthese von (−)‐Pantofuranoid E belegt wird.

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Evaluation of crystallinity and drug release stability of directly compressed theophylline hydrophilic matrix tablets stored under varied moisture conditions

Cited by 32 publications

References 11 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

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

Computationally‐Assisted Approach to the Vibrational Spectra of Molecular Crystals: Study of Hydrogen‐Bonding and Pseudo‐Polymorphism

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