Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry

Lamm, Matthew S.; DiNunzio, James; Khawaja, Nazia N.; Crocker, Louis S.; Pecora, Anthony

doi:10.1208/s12249-015-0387-9

Cited by 27 publications

(11 citation statements)

References 25 publications

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“…In the melt granulation process drug is granulated with the melted lipid binder under pressure. High pressure treatment can affect the crystal morphology, crystal size distribution, polymorphic properties [24]. Since the drug is covered with lipid binder, the physical and chemical stability of meltable binder plays an important role in final stability of the dosage form.…”

Section: Resultsmentioning

confidence: 99%

Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

Gejage¹,

Pawar²,

Amin³

et al. 2018

Preprint

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Mere similar grades of same excipients manufactured by two different manufacturers often differ significantly that they even have an impact on the variations in final product or dosage form. Solid lipids are one of the most available options as matrix former in sustained drug delivery. Due to their chemical and physical complexity, lipids may exhibit a complex behaviour (i.e. melting crystallization and polymorphism). The aim of this study was to evaluate the physical and chemical properties of two Glyceryl Monostearate (GMS) lipids (Geleol from Gattefosse and Capmul GMS 50K from Abitec Corp. USA) and how these properties may affect during melt granulation process for sustained release applications. Thermal processing was applied on GMS samples to understand the polymorphic nature and suitability as meltable binders. Niacin was used as model drug. A thorough evaluation of GMS samples and sustained release tablets was undertaken using analytical techniques such as differential scanning calorimetry (DSC), X-ray diffraction (XRD). Moreover, melt viscosity study assisted to apprehend the behaviour of GMS samples in hot melt extrusion processing. Surface morphology of the drug and extruded granules examined via SEM and AFM revealed high level of surface interaction and dense structure of drug inside lipid matrix. The DSC and XRD study confirmed that Geleol could not withstand the heat treatment applied during thecontinuous melt granulation processing. The shifting of stable β form to an unstable α form in Geleol was detected. In the contrary case, Capmul GMS 50K was able to withstand the heat treatment supported by the applied analytical techniques. Nonetheless,both GMS samples perform differently in final dosage form. This change in stable β form to an unstable α form affected dissolution profiles at 3 months storage in accelerated condition. This study helped to interpret the complex solid-state behaviour of solid lipid extrudates with different compositions, in order to the simply and outline a suitable formulation strategy for the development of lipid-based oral dosage forms.

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Section: Resultsmentioning

confidence: 99%

Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

Gejage¹,

Pawar²,

Amin³

et al. 2018

Preprint

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“…In a recent work, AFR and MDSC were used to select the best operating conditions for obtaining a single-phase amorphous material, by extruding d - α -tocopherol polyethylene glycol 1000 succinate (TPGS 1000) with copovidone in a co-rotating twin-screw extruder. Several process parameters such as screw speed, cooling conditions, and composition were correlated to the solid physical state of the mix [ 73 ]. At 10% w / w of TPGS 1000 in copovidone and a screw speed of 600 rpm, a single phase was observed, while when the screw speed was decreased to 300 rpm, a separation phase was evident, because of insufficient mixing.…”

Section: Introductionmentioning

confidence: 99%

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

et al. 2018

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Hot-melt extrusion (HME) is a well-accepted and extensively studied method for preparing numerous types of drug delivery systems and dosage forms. It offers several advantages: no solvents are required, it is easy to scale up and employ on the industrial level, and, in particular, it offers the possibility of improving drug bioavailability. HME involves the mixing of a drug with one or more excipients, in general polymers and even plasticizers, which can melt, often forming a solid dispersion of the drug in the polymer. The molten mass is extruded and cooled, giving rise to a solid material with designed properties. This process, which can be realized using different kinds of special equipment, may involve modifications in the drug physicochemical properties, such as chemical, thermal and mechanical characteristics thus affecting the drug physicochemical stability and bioavailability. During process optimization, the evaluation of the drug solid state and stability is thus of paramount importance to guarantee stable drug properties for the duration of the drug product shelf life. This manuscript reviews the most important physicochemical factors that should be investigated while designing and optimizing a hot melt extrusion process, and by extension, during the different pre-formulation, formulation and process, and post-formulation phases. It offers a comprehensive evaluation of the chemical and thermal stability of extrudates, the solid physical state of extrudates, possible drug-polymer interactions, the miscibility/solubility of the drug-polymer system, the rheological properties of extrudates, the physicomechanical properties of films produced by hot melt extrusion, and drug particle dissolution from extrudates. It draws upon the last ten years of research, extending inquiry as broadly as possible.

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“…Therefore, stability studies can be carried out within hours, instead of within weeks [ 7 , 8 ]. Beyond mapping of spatial drug-polymer distributions, SPMs enable to concertedly probe spectroscopic, mechanical and thermal properties and thereby enlighten complex structure-property relations in a direct manner [ 9 , 10 ]. A disadvantage of SPMs is that only smooth and small surface areas are accessible with the SPM sensor.…”

Section: Introductionmentioning

confidence: 99%

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

et al. 2018

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Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials.

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Assessing Mixing Quality of a Copovidone-TPGS Hot Melt Extrusion Process with Atomic Force Microscopy and Differential Scanning Calorimetry

Cited by 27 publications

References 25 publications

Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

Influence of Different Meltable Binders on the Solid-State Behaviour and Dissolution Profiles of Solid Lipid Extrudates Processed Via Continuous Hot Melt Granulation

Hot Melt Extrusion: Highlighting Physicochemical Factors to Be Investigated While Designing and Optimizing a Hot Melt Extrusion Process

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion

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