Continuous manufacturing of delta mannitol by cospray drying with PVP

Bockstal, Pieter-Jan Van; Snick, B. Van; Peeters, Elisabeth; Monteyne, Tinne; Gomes, Patrícia; Beer, Thomas De; Remon, Jean Paul; Vanhoorne, Valérie

doi:10.1016/j.ijpharm.2016.02.001

Cited by 30 publications

(16 citation statements)

References 16 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%

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%

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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“…Vanhoorne et al [46] co-spray dried paracetamol with mannitol and PVP. Compaction properties of the co-spray dried powders were compared to physical mixtures for compositions containing 75% paracetamol, 20-25% spray-dried mannitol, and 0-5% PVP.…”

Section: Direct Compression Of Co-spray Dried Apis With Excipientsmentioning

confidence: 99%

Spray Drying for Direct Compression of Pharmaceuticals

et al. 2021

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Tableting by direct compression (DC) is one of the simplest and most cost-effective drug manufacturing approaches. However, most active pharmaceutical ingredients (APIs) and excipients lack the compression and flow properties required to meet the needs of high-speed industrial tablet presses. Therefore, the majority of DC APIs and excipients are modified via processing/co-processing particle engineering techniques to boost their properties. Spray drying is one of the most commonly employed techniques to prepare DC grades of APIs and excipients with prominent advantages. This review aims to present an overview of the commercially marketed and investigationally-prepared DC APIs and excipients produced by spray drying.

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“…Both αand δ-form of mannitol were found to be chemically and physically stable for at least 5 years when stored at 25 o C and 43% relative humidity [47]. Recently, co-spray drying of an aqueous solution of mannitol with PVP in a ratio 4:1 was reported to produce the δ-form of mannitol [48].…”

Section: Solid State Characterizationmentioning

confidence: 99%

Preparation of respirable nanoparticle agglomerates of the low melting and ductile drug ibuprofen: Impact of formulation parameters

Malamatari¹,

Somavarapu²,

Kachrimanis

et al. 2017

Powder Technology

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Ductile and low melting point drugs exhibit challenging behaviour during both particle size reduction and spray drying as considerable amount of heat is involved in both processes. In this study, a systematic approach was employed to understand the preparation and in-vitro performance of respirable nanoparticle agglomerates by coupling wet milling and spray drying for ibuprofen, which is a drug with a low melting point and challenging mechanical properties. Wet milling in the presence of two stabilizers differing in their thermal properties and subsequent spray drying of the suspensions were employed after the addition of mannitol and/or leucine. The effects of the stabilizer type and the amounts of mannitol (matrix former) and leucine (dispersibility enhancer), on the yield of the process, the particle size, the redispersibility (i.e. reformation of nanoparticles upon rehydration) and the aerosolization (fine particle fraction, FPF%) of the nanoparticle agglomerates were evaluated using standard least squares model and a 2 3 full factorial design (3 factors at 2 levels plus four centre points). All factors investigated were found to have a significant effect on the yield of nanoparticle agglomerates (p<0.05). The size of the nanoparticle agglomerates was mainly dependent on the leucine to drug ratio and the type of stabilizer (p<0.05), while mannitol to drug ratio was the only significant factor affecting the redispersibility of the formulations (p<0.05). The FPF%, determined using a fast screening impactor, was found to be dependent on both the leucine and mannitol to drug ratio (p<0.05). This study demonstrates the successful preparation of respirable nanoparticle agglomerates of low melting point and ductile ibuprofen and the usefulness of the design of experiments as a tool to understand the impact of the formulation parameters on their fabrication and in-vitro performance.

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Continuous manufacturing of delta mannitol by cospray drying with PVP

Cited by 30 publications

References 16 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

Spray Drying for Direct Compression of Pharmaceuticals

Preparation of respirable nanoparticle agglomerates of the low melting and ductile drug ibuprofen: Impact of formulation parameters

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