A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms

Leane, Michael; Pitt, Kendal; Reynolds, Gavin K.

doi:10.3109/10837450.2014.954728

Cited by 226 publications

(97 citation statements)

References 36 publications

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“…Properties of the API, such as small particle size [8, 9] and needle-like morphology [10, 11] can lead to processing limitations such as poor flowability [12], difficulties with blending [9] as well as undesirable adhesion [13] to surfaces such as tablet punches or feeder walls [14]. These issues are addressed by selecting an appropriate processing route and/or by adding agents like glidants, lubricants or surfactants [15–18].…”

Section: Introductionmentioning

confidence: 99%

A Review of Disintegration Mechanisms and Measurement Techniques

2017

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Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

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Section: Introductionmentioning

confidence: 99%

A Review of Disintegration Mechanisms and Measurement Techniques

2017

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“…A variety of excipients, such as diluents, disintegrants, surfactants and lubricants, are mixed to form uniform blends of suitable flowability and compactibility that do not stick to the surfaces of feeder walls, tablet punches or other processing equipment and do not demix during processing [1]. Tablet formulators also have to consider the desired release profile of the dosage form, in particular whether the drug should be released immediately after administration or the drug release should be controlled over a longer period of time.…”

Section: Introductionmentioning

confidence: 99%

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Markl

Sauerwein

Goodwin³

et al. 2017

Pharm Res

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PurposeThe aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale.MethodsSamples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch.ResultsThe disintegration time (R 2 = 0.86) and API dissolved after 15 min (R 2 = 0.96) linearly correlates with the effective refractive index, n eff, measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff, we observed a better correlation with dissolution after 20 min (R 2 = 0.96) and a weaker correlation with disintegration (R 2 = 0.83) compared to n eff.ConclusionThe measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-017-2108-4) contains supplementary material, which is available to authorized users.

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“…The boundary between the 2 subclasses is determined by the solubility-limited absorbable dose, which is calculated from an estimate of small intestine solubility, fluid volume, and a permeability-dependent multiplier. 19 Leane et al 24 have been working on developing a Manufacturing Classification System, a supportive tool to help rational selection of an optimal processing route for a specific API. The system is, similar to the BCS, based on 4 classes with increasing risk associated with each class.…”

Section: Classification Systemsmentioning

confidence: 99%