Stability and several physical properties of amorphous and crystalline forms of indomethacin.

Imaizumi, Hiroyuki; Nambu, Naoki; Nagai, Tsuneji

doi:10.1248/cpb.28.2565

Cited by 115 publications

(55 citation statements)

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“…amorphous pharmaceuticals, including partially crystalline lactose and microcrystalline cellulose, the formation of hard compacts has been attributed to plastic deformation during compression. 21,22 Amorphous indomethacin, 23 partially crystalline lactose, 21 and amorphous β-cyclodextrin 24 yielded harder tablets than did their crystalline counterparts. 21 Thus, plastic deformation during compression of the processed anhydrate (Case 3 in Scheme 2) may be responsible for the higher tablet hardness and the longer disintegration time (compare formulation no.…”

Section: Dissolution Of Tabletsmentioning

confidence: 99%

“…Therefore, consistent with literature reports, the tablet properties (hardness, disintegration, and dissolution) seem to be substantially influenced by the crystallinity of the drug. 21,23 The various stresses encountered during pharmaceutical processing can bring about a decrease in drug crystallinity. For example, both milling and compression are known to cause a decrease in the degree of crystallinity.…”

Section: Dissolution Of Tabletsmentioning

confidence: 99%

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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: Dissolution Of Tabletsmentioning

confidence: 99%

Section: Dissolution Of Tabletsmentioning

confidence: 99%

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

Debnath

Suryanarayanan

2004

AAPS PharmSciTech

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“…Fig. 2 shows the X-ray diffractograms of pure indomethacin and pure excipients, a physical mixture of the conventional formulation (indomethacin, avicel and silica) and liquisolid formula- (16)(17)(18)(19). As it is clear from Fig.…”

Section: Resultsmentioning

confidence: 99%

Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and evaluation of their physicochemical properties

Javadzadeh¹,

Siahi²,

Asnaashari³

et al. 2007

Acta Pharmaceutica

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The potential of liquisolid systems to improve the dissolution properties of a water-insoluble agent (indomethacin) was investigated. In this study, different formulations of liquisolid tablets using different co-solvents (non-volatile solvents) were prepared and the effect of aging on the dissolution behaviour of indomethacin liquisolid compacts was investigated. To evaluate any interaction between indomethacin and the other components in liquisolid formulations, X-ray powder diffraction (XPD) and differential scanning calorimetry (DSC) were used. Dissolution test was carried out at two different pH, 1.2 and 7.2, to simulate the stomach or intestine fluid, respectively. The results showed that liquisolid formulations exhibited significantly higher drug dissolution rates at pH 1.2 and 7.2 compared to compacts prepared by the direct compression technique. The enhanced rate of indomethacin dissolution from liquisolid tablets was probably due to an increase in wetting properties and surface area of drug particles available for dissolution. In order to investigate the effect of aging on the hardness and dissolution rate of liquisolid compacts, the formulations were stored at 25°C /75% relative humidity for a period of 12 months. The results showed that aging had no significant effect on dissolution profiles of liquisolid tablets. Liquisolid compacts containing propylene glycol as vehicle produced higher dissolution rates in comparison with liquisolid compacts containing PEG 400 or Tween 80 of the same concentration. The DSC and XPD results showed no changes in crystallinity of the drug and interaction between indomethacin and excipients (Avicel and silica) during the process.

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“…Spray-Dry Solid Dispersion of Griseofulvin (20% Drug Load) SDD preparation followed the procedure reported previously (21). Griseofulvin (1.0 g) and HPMCAS (4.0 g) were dissolved as a 5 wt% solution in acetone.…”

Section: Materials and Instrumentation Systemmentioning

confidence: 99%

“…In order to overcome the throughput issues with the spray-drying process, newer processes such as solvent casting (fast evaporation) and freeze-drying (lyophilization) have been developed for manufacturing ASDs at smaller scales. These two simple processes can be executed on the milligram scale with good efficiency (1,2,(20)(21)(22)(23)(24)(25)(26) and have been widely adopted in drug discovery setting (1,2,24,25).…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

Chiang¹,

Cui²,

Ran³

et al. 2013

AAPS J

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Abstract. Drug polymer-based amorphous solid dispersions (ASD) are widely used in the pharmaceutical industry to improve bioavailability for poorly water-soluble compounds. Spray-drying is the most common process involved in the manufacturing of ASD material. However, spray-drying involves a high investment of material quantity and time. Lower investment manufacturing processes such as fast evaporation and freeze-drying (lyophilization) have been developed to manufacture ASD at the bench level. The general belief is that the overall performance of ASD material is thermodynamically driven and should be independent of the manufacturing process. However, no formal comparison has been made to assess the in vivo performance of material generated by different processes. This study compares the in vitro and in vivo properties of ASD material generated by fast evaporation, lyophilization, and spray-drying methods using griseofulvin as a model compound and hydroxypropyl methylcellulose acetate succinate as the polymer matrix. Our data suggest that despite minor differences in the formulation release properties and stability of the ASD materials, the overall exposure is comparable between the three manufacturing processes under the conditions examined. These results suggest that fast evaporation and lyophilization may be suitable to generate ASD material for oral evaluation. However, caution should be exercised since the general applicability of the present findings will need to be further evaluated.

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Stability and several physical properties of amorphous and crystalline forms of indomethacin.

Cited by 115 publications

References 1 publication

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

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

Liquisolid technique as a tool for enhancement of poorly water-soluble drugs and evaluation of their physicochemical properties

In Vitro and In Vivo Evaluation of Amorphous Solid Dispersions Generated by Different Bench-Scale Processes, Using Griseofulvin as a Model Compound

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