Energy/Temperature Diagram and Compression Behavior of the Polymorphs of d-Mannitol

Burger, A.; Henck, Jan‐Olav; Hetz, Silvia; Rollinger, Judith M.; Weissnicht, Andrea A.; Stöttner, Hemma

doi:10.1002/(sici)1520-6017(200004)89:4<457::aid-jps3>3.0.co;2-g

Cited by 316 publications

(262 citation statements)

References 20 publications

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“…Superior compaction properties of δ-mannitol were also reported by Burger et al, Wagner et al. and Vanhoorne et al [23,34,42]. The TS of granules derived from β-mannitol starting material did not exceed 1.6 MPa and was independent of the applied MCP.…”

Section: Tabletability and Compression Mechanismsupporting

confidence: 67%

“…This is noteworthy since Table 2 and it is clear that milling did not change the polymorphic content of the samples. Stability of δ-mannitol, although thermodynamically the least stable mannitol polymorph, under mechanical stress was also demonstrated by Burger et al [34].…”

Section: Solid State Characterizationsupporting

confidence: 54%

“…Moreover, a small peak at 9.90°, selective for δ-mannitol, in the diffractograms of runs 5, 12, 13, 18 and 19 indicated a significant residual percentage of δ-mannitol in these samples [21,22,30,34,36,37]. The overall lower intensity of the peaks in the diffractograms of the granules was attributed to a different crystal habit of the granules in comparison to the reference materials (powders) [38].…”

Section: Solid State Characterizationmentioning

confidence: 95%

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Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Vanhoorne

Bekaert

Peeters

et al. 2016

International Journal of Pharmaceutics

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To refer to or to cite this work, please use the citation to the published version:Vanhoorne V., Bekaert B., Peeters E., De Beer T., Remon J.P., Vervaet C. (2016) Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation. International Journal of Pharmaceutics 506 13-24 DOI: 10.1016/j.ijpharm.2016.04.025 AbstractIn most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness.Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400 -900 rpm), granulation temperature (25 -40 °C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma TM -25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ-to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, lesssoluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different.

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Section: Tabletability and Compression Mechanismsupporting

confidence: 67%

Section: Solid State Characterizationsupporting

confidence: 54%

Section: Solid State Characterizationmentioning

confidence: 95%

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Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Vanhoorne

Bekaert

Peeters

et al. 2016

International Journal of Pharmaceutics

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“…During lyophilisation, mannitol was shown to crystallise as three common stable anhydrous polymorphic forms (i.e. α, β and δ) (Bauer et al, 2000;Berman et al, 1968;Botez et al, 2003;Burger et al, 2000;Kim et al, 1968) or as mannitol hemihydrate (Cavatur and Suryanarayanan, 1998;Cavatur et al, 2002;De Beer et al, 2007;Nunes et al, 2004;RomeroTorres et al, 2007;Yu et al, 1999). The polymorphic form of lyophilised mannitol was shown to have an effect in the stability of the lyophilised product during its storage (Cao et al, 2006;De Beer et al, 2009Pisano et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…(Yu et al, 1999) showed the secondary drying conditions during freeze-drying as important parameters for the removal of the mannitol hemihydrate form. (Cannon and Trappler, 1999) showed slow cooling rates to promote the formation of α-mannitol. The use of surfactants, e.g.…”

Section: Introductionmentioning

confidence: 99%

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Kaialy

Mawlud

2016

International Journal of Pharmaceutics

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Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. Abbreviations∆H0, Endothermic enthalpy of CM melting; ∆Hs, Endothermic enthalpy of LM melting; ANOVA, One-way analysis of variance; API, Active pharmaceutical ingredient; c.opt, Optimal concentration; CI, Carr's index; CM, Commercial mannitol; Cman, Concentration of mannitol; d10%, particle size at 10% volume distribution; d50%, particle size at 50% volume distribution; d90%, particle size at 90% volume distribution; Db, Bulk density, DE, Dissolution efficiency; DSC, Differential scanning calorimeter; Dt, tap density; EB, Ease of breakage; Eq, Equation; FT-IR, Fourier transform infrared; GI, Gastro intestinal; HSD, Honestly Significant Difference; I, Relative intensity; Iamorphous, the input to the intensity from the amorphous region; Icrystalline, the input to the intensity from the crystalline region; LM, Lyophilised mannitol; MDR, Mean dissolution rate; MDT, Mean dissolution time; P, Statistical probability; PXRD, Powder X-ray diffraction; Q10min, The mean percentage of drug dissolved in the first 10 min; Q30min, The mean percentage of drug dissolved in the first 30 min; Q4min, The mean percentage of drug dissolved in the first 4 min; Q50min; The mean percentage of drug dissolved in the first 50 min; RDB, Relative degree of breakage;

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Polymorphs, Solvates and Hydrates

Threlfall

2001

Handbook of Vibrational Spectroscopy

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The sections in this article are Introduction – The Nature of Polymorphism and Solvation Mid‐Infrared Spectroscopy Quantitative Mid‐Infrared Measurements Burger's Infrared Rule Stability Near‐Infrared Spectroscopy R aman Spectroscopy Infrared and R aman Microspectroscopy

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Energy/Temperature Diagram and Compression Behavior of the Polymorphs of d-Mannitol

Cited by 316 publications

References 20 publications

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation

Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Polymorphs, Solvates and Hydrates

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