Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

Objective: The aim of this study was to develop and optimize the formulation of tablets containing Aquilaria crassna extract using the direct compression method.Methods: D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimize the A. crassna tablet formulation. The weight variation (Y1), disintegration time (Y2), hardness (Y3) and friability (Y4) were investigated with respect to three independent variables including % dicalcium phosphate anhydrous (DCPA) in filler (X1), % filler (X2) and % croscarmellose sodium (CCNa) (X3). The dissolution study of the optimized A. crassna tablets were investigated in simulated gastric fluid (SGF) (pH 1.2) using a validated high-performance liquid chromatography (HPLC) method for mangiferin analysis.Results: All investigation factors were found to have significant effects on the physical properties of A. crassna tablet. The tablet hardness and the disintegration time increased in positive relations with the ratios of DCPA. The results exhibited the negative relations between disintegration time and the percentages of CCNa. The optimized A. crassna tablet formulation which included 35 % (w/w) DCPA in filler, 60 % (w/w) filler and 7% (w/w) CCNa possessed the weight variation of 1.38 % (w/w), the disintegration time of 6.29 min, the hardness of 85.63 N and the friability of 0.41 % (w/w). The optimized A. crassna tablet formulation was experimentally examined which demonstrated a good agreement between the experimental and predicted values. Mangiferin was found to release completely from the optimized A. crassna tablets within 30 min. Conclusion:The cause-effect relations and optimization of A. crassna tablet formulation were investigated and reported for the first time. The A. crassna spray-dried extract could be formulated into tablet by direct compression method with good mechanical properties and acceptable release profile.

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“…As a result, SMCC could improve the hardness of the A. crassna tablet [21]. Similar results were previously reported by Solaiman A [22,23]. …”

Section: Effect Of Variables On Hardnesssupporting

confidence: 89%

Study on Cause-Effect Relations and Optimization of Tablets Containing Aquilaria Crassna Spray-Dried Extract

Huong

Monsatta

Hanh

et al. 2017

Int J Pharm Pharm Sci

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“…PVP is frequently used in HME to enhance the dissolution pattern of poorly soluble molecules (24)(25)(26)(27)(28). TGA thermographs ( Figs.…”

Section: Resultsmentioning

confidence: 99%

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets

et al. 2016

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2 ABSTRACTPurpose. The fabrication of a ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing.Methods. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a capletshaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus.Results. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication immediate release tablets at temperatures as low as 110 o C. The integrity of two models drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Conclusions.Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

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“…Initiated by the Food and Drug Administration (FDA) in order to increase the robustness and quality of a product, pharmaceutical quality-by-design (QbD) was introduced as a strategic product development approach which considers both formulation and process-related factors that affect the critical quality attributes of the final product (Patwardhan et al, 2015). This already resulted in a few interesting approaches to implement QbD in pharmaceutical melt extrusion processes (Agrawal et al, 2016;Islam et al, 2014;Patwardhan et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Downstream processing from hot-melt extrusion towards tablets: A quality by design approach

Grymonpré

Bostijn

Herck

et al. 2017

International Journal of Pharmaceutics

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Since the concept of continuous processing is gaining momentum in pharmaceutical manufacturing, a thorough understanding on how process and formulation parameters can impact the critical quality attributes (CQA) of the end product is more than ever required. This study was designed to screen the influence of process parameters and drug load during HME on both extrudate properties and tableting behaviour of an amorphous solid dispersion formulation using a quality-by-design (QbD) approach. A full factorial experimental design with 19 experiments was used to evaluate the effect of several process variables (barrel temperature: 160-200°C, screw speed: 50-200rpm, throughput: 0.2-0.5kg/h) and drug load (0-20%) as formulation parameter on the hot-melt extrusion (HME) process, extrudate and tablet quality of Soluplus-Celecoxib amorphous solid dispersions. A prominent impact of the formulation parameter on the CQA of the extrudates (i.e. solid state properties, moisture content, particle size distribution) and tablets (i.e. tabletability, compactibility, fragmentary behaviour, elastic recovery) was discovered. The resistance of the polymer matrix to thermo-mechanical stress during HME was confirmed throughout the experimental design space. In addition, the suitability of Raman spectroscopy as verification method for the active pharmaceutical ingredient (API) concentration in solid dispersions was evaluated. Incorporation of the Raman spectroscopy data in a PLS model enabled API quantification in the extrudate powders with none of the DOE-experiments resulting in extrudates with a CEL content deviating>3% of the label claim. This research paper emphasized that HME is a robust process throughout the experimental design space for obtaining amorphous glassy solutions and for tabletting of such formulations since only minimal impact of the process parameters was detected on the extrudate and tablet properties. However, the quality of extrudates and tablets can be optimized by adjusting specific formulations parameters (e.g. drug load).

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Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach

Cited by 64 publications

References 29 publications

Study on Cause-Effect Relations and Optimization of Tablets Containing Aquilaria Crassna Spray-Dried Extract

Study on Cause-Effect Relations and Optimization of Tablets Containing Aquilaria Crassna Spray-Dried Extract

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets

Downstream processing from hot-melt extrusion towards tablets: A quality by design approach

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