Scale up of Semisolid Dosage Forms Manufacturing Based on Process Understanding: from Lab to Industrial Scale

Heugten, A.J.P. van; Vromans, Herman

doi:10.1208/s12249-018-1063-7

Cited by 10 publications

(9 citation statements)

References 9 publications

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“…Furthermore, Van Heugten and colleagues have evaluated the influence of filling temperature on an ointment yield stress. Based on this knowledge, the authors were able to establish an optimal filling viscosity range, which, in turn, enabled a successful filling operation with minimal weight variation and a product with the desired yield stress [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Simões

Miranda

Cardoso³

et al. 2020

Pharmaceutics

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The increasing demand for product and process understanding as an active pursuit in the quality guideline Q8 and, more recently, on the draft guideline on quality and equivalence of topical products, has unveiled the tremendous potential of rheology methods as a tool for microstructure characterization of topical semisolid dosage forms. Accordingly, procedure standardization is a dire need. This work aimed at developing and validating a methodology tutorial for rheology analysis. A 1% hydrocortisone cream was used as model cream formulation. Through a risk assessment analysis, the impact of selected critical method variables (geometry, temperature and application mode) was estimated in a broad range of rheological critical analytical attributes—zero-shear viscosity, upper-shear thinning viscosity, lower-shear thinning viscosity, infinite-shear viscosity, rotational yield point, thixotropic relative area, linear viscoelastic region, oscillatory yield point, storage modulus, loss modulus, and loss tangent. The proposed validation of the approach included the rheometer qualification, followed by the validation of numerous operational critical parameters regarding a rheology profile acquisition. The thixotropic relative area, oscillatory yield point, flow point and viscosity related endpoints proved to be highly sensitive and discriminatory parameters. This rationale provided a standard framework for the development of a reliable and robust rheology profile acquisition.

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Section: Introductionmentioning

confidence: 99%

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Simões

Miranda

Cardoso³

et al. 2020

Pharmaceutics

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“…Unlike DSD, the conventional standard designs such as fractional factorial and Plackett-Burman designs are generally incapable of avoiding potential confounding effects caused by the combination of two-factor interactions and some main effects. 12) We believe that DSD can provide a reasonable solution to overcome the problems that might arise in a screening study caused by confounding errors. In addition to main effects and two-factor interactions, DSD allows us to evaluate the quadratic effects of factors.…”

Section: Resultsmentioning

confidence: 99%

“…The dosage forms that have been investigated are reported to be oral disintegrating films, 9) cross-linked chitosan disc-modified drug release, 10) intranasal transferosomal mucoadhesive gel formulation, 11) and ointment formulation. 12) In addition to these, van Heugten and Vromans introduced DSD to scale up a study of semisolid dosage forms to understand the manufacturing processes using a QbD approach. 13) Goldman et al used DSD for optimization of a manufacturing process involving lyophilization for the manufacturing of monoclonal antibody drug products.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, DSD is attracting considerable attention as a promising technical method for the QbD approach. To date, DSD has been applied to the preparation of a wide range of dosage forms including oral disintegrating films, 9) modifiedrelease drug products, 10) intranasal gel formulations, 11) semisolid dosage forms, 12,13) and lyophilized products. 14) However, to our knowledge, there is no pharmaceutical study comparing analytical results between DSD and conventional DOE methods.…”

Section: Introductionmentioning

confidence: 99%

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The Usefulness of Definitive Screening Design for a Quality by Design Approach as Demonstrated by a Pharmaceutical Study of Orally Disintegrating Tablet

Takagaki

Ito

Arai

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Definitive screening design (DSD) is a new class of small three-level experimental design that is attracting much attention as a technical tool of a quality by design (QbD) approach. The purpose of this study is to examine the usefulness of DSD for QbD through a pharmaceutical study on the preparation of ethenzamidecontaining orally disintegrating tablet. Model tablets were prepared by directly compressing the mixture of the active pharmaceutical ingredient (API) and excipients. The five evaluated factors assigned to DSD were: the contents of API (X1) and lubricant (X2), and the compression force (X3) of the tableting process, the mixing time (X4), and the filling ratio of powder in the V-type mixer (X5). After tablet preparation, hardness and disintegration time were measured. The same experiments were performed by using the conventional design of experiments [i.e., L8 and L16 orthogonal array designs and central composite design (CCD)]. Results showed that DSD successfully clarified how various factors contribute to tablet properties. Moreover, the analysis result from DSD agreed well with those from the L8 and L16 experiments. In additional experiments, response surfaces for tablet properties were created by DSD. Compared with the response surfaces created by CCD, DSD could produce reliable response surfaces for its smaller number of experiments. We conclude that DSD is a powerful tool for implementing pharmaceutical studies including the QbD approach.

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“…To date, DSD has been used in a wide range of pharmaceutical formulation studies to screen crucial manufacturing process variables. The dosage forms include oral disintegrating films, 9) modifiedrelease drug products, 10) intranasal gel formulations, 11) semisolid dosage forms 12,13) and lyophilized products. 14) Recently, we have investigated the usefulness of DSD for use in the QbD approach through a case study on the formulation design of ethenzamide-containing orally disintegrating tablet.…”

Section: Introductionmentioning

confidence: 99%

Effects of Manufacturing Process Variables on the Tablet Weight Variation of Mini-tablets Clarified by a Definitive Screening Design

Usuda

Masukawa²,

Leong

et al. 2021

Chem. Pharm. Bull.

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This study investigated the effect of manufacturing process variables of mini-tablets, in particular, the effect of process variables concerning fluidized bed granulation on tablet weight variation. Test granules were produced with different granulation conditions according to a definitive screening design (DSD). The five evaluated factors assigned to DSD were: the grinding speed of the sample mill at the grinding process of the active pharmaceutical ingredient (X1), microcrystalline cellulose content in granules (X2), inlet air temperature (X3), binder concentration (X4) and the spray speed of the binder solution (X5) at the granulation process. First, the relationships between the evaluated factors and the granule properties were investigated. As a result of the DSD analysis, the mode of action of granulation parameters on the granule properties was fully characterized. Subsequently, the variation in tablet weight was examined. In addition to mini-tablets (3 mm diameter), this experiment assessed regular tablets (8 mm diameter). From the results for regular tablets, the variation in tablet weight was affected by the flowability of granules. By contrast, regarding the mini-tablets, no significant effect on the variation of tablet weight was found from the evaluated factors. From this result, this study further focused on other important factors besides the granulation process, and then the effect of the die-hole position of the multiple-tip tooling on tablet weight variation was proven to be significant. Our findings provide a better understanding of manufacturing mini-tablets.

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Scale up of Semisolid Dosage Forms Manufacturing Based on Process Understanding: from Lab to Industrial Scale

Cited by 10 publications

References 9 publications

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

Rheology by Design: A Regulatory Tutorial for Analytical Method Validation

The Usefulness of Definitive Screening Design for a Quality by Design Approach as Demonstrated by a Pharmaceutical Study of Orally Disintegrating Tablet

Effects of Manufacturing Process Variables on the Tablet Weight Variation of Mini-tablets Clarified by a Definitive Screening Design

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