Development of a two-step tier-2 dissolution method for blinded overencapsulated erlotinib tablets using UV fiber optic detection

Lu, Xujin; Xiao, Baiming; Lo, Lili; Bolgar, Mark S.; Lloyd, David K.

doi:10.1016/j.jpba.2011.04.026

Cited by 9 publications

(13 citation statements)

References 13 publications

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“…Some additional considerations may apply to a pre-treatment procedure (54). For specificity, non-interference of the enzyme should be confirmed using the pre-treatment procedure.…”

Section: Pre-treatment Step Methods Validationmentioning

confidence: 99%

Use of Enzymes in the Dissolution Testing of Gelatin Capsules and Gelatin-Coated Tablets-Revisions to Dissolution <711> and Disintegration and Dissolution of Dietary Supplements <2040>

Gray¹,

Marques²,

Cole³

et al. 2014

Dissolution Technol.

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A revision to the general chapters Dissolution <711> and Disintegration and Dissolution of Dietary Supplements <2040> is being proposed to address the shortcomings of the current chapters regarding the use of enzymes in the dissolution test of gelatin capsules or gelatin-coated tablets. The recommendations are to use the enzymes pepsin (medium with pH equal to or below 4.0), papain or bromelain (medium with pH above 4.0 and below 6.8), and pancreatin (medium with pH equal to or above 6.8) if the dosage form does not comply to the appropriate Acceptance Table or, in the case of dietary supplements, appropriate Tolerances requirements due to the presence of cross-linking in the gelatin. Also, the revision clarifies how the enzyme activity should be determined, the amount of enzymes to be added to the medium, and a pre-treatment procedure to be used when the dissolution medium contains surfactant or any other ingredient known or suspect to inactivate the enzyme being used. This Stimuli article provides the rationale for these revisions and presents data to support the recommendations being made. Readers are encouraged to send any comments, questions, suggestions or data to the corresponding author. Also, see the section Other Related Revisions at the end of this article for information on other related general chapters and monographs.

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“…Some additional considerations may apply to a pre-treatment procedure (54). For specificity, non-interference of the enzyme should be confirmed using the pre-treatment procedure.…”

Section: Pre-treatment Step Methods Validationmentioning

confidence: 99%

Use of Enzymes in the Dissolution Testing of Gelatin Capsules and Gelatin-Coated Tablets-Revisions to Dissolution <711> and Disintegration and Dissolution of Dietary Supplements <2040>

Gray¹,

Marques²,

Cole³

et al. 2014

Dissolution Technol.

View full text Add to dashboard Cite

show abstract

“…The formation of a pellicle in most situations may not be so obvious, especially for those moderately or lightly stressed gelatin capsules and those from stability studies when cross-linking starts to form and just starts to affect the drug release during dissolution testing. Figure 3 shows a dissolution run of over-encapsulated Erlotinib tablets in HGC shells (40 As often noted during dissolution testing, cross-linking is heterogeneous. In the same batch, some capsules can cross-link and some may not.…”

Section: Visual Observationmentioning

confidence: 96%

“…To overcome the effect of the surfactants on enzymatic activity, the USP Tier-2 dissolution test has been studied in two steps (40,41). In the first step, the cross-linked gelatin capsules are pretreated for a short time using the medium containing the enzyme but without the surfactant.…”

Section: Enzyme Activity and Performance Formentioning

confidence: 99%

“…However, before USP <1094> was published, gelatin capsule cross-linking phenomena, linked to decreased drug release, were described in several different ways (Table 1). The most frequent observation is a significant increase in disintegration time (8,11,38,40,41). The other observations are the formation of a gellike film (11,14,31,40), swollen, rubbery elastic matrix (8,14,22), or gelling with embedded drug blend (41).…”

Section: Visual Observationmentioning

confidence: 99%

“…The most frequent observation is a significant increase in disintegration time (8,11,38,40,41). The other observations are the formation of a gellike film (11,14,31,40), swollen, rubbery elastic matrix (8,14,22), or gelling with embedded drug blend (41). The differences in the reported descriptions might be due to the different experiences of the analysts who performed the dissolution testing.…”

Section: Visual Observationmentioning

confidence: 99%

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Dissolution of Gelatin Capsules: Evidence and Confirmation of Cross-Linking

Lu¹,

Shah²

2017

Dissolution Technol.

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Cross-linking is a common problem in the dissolution of gelatin capsules. Cross-linking is characterized by a bridge across the peptide backbone of the gelatin molecule which creates water insoluble membranes or pellicles during dissolution testing. The chemical covalent bonding between gelatin chains is typically triggered by catalytic amounts of aldehyde and/or from exposure to high temperature and humidity. Cross-linking gelatin capsules results in a slower release of the drug or no release at all in common dissolution media. If the gelatin capsule dissolution fails acceptance criteria due to evidence of cross-linking, the US Pharmacopeia allows the use of enzymes in the dissolution medium and requires twotier dissolution testing. Studies have shown that drugs from cross-linked capsules are available in vivo to the patient, justifying the use of enzymes in the in vitro dissolution test. The literature contains several examples supporting evidence of cross-linking. However, confirming the degree of cross-linking continues to be a practical challenge due to a lack of quantitative procedures for measuring the extent of cross-linking and variability in options for formulations, excipients, level and types of stresses, and the experience level of the analysts. This article reviews the methodologies to confirm the evidence of cross-linking such as visual observation, capsule shell switch test, and spectroscopic determination of cross-linking, with an aim to facilitate the discussion and establishment of an acceptable standard approach.

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Density functional methods study on the structures and spectral characteristics for pharmacophoric conformers, metabolites, and combined fragments of Erlotinib

et al. 2022

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Development of a two-step tier-2 dissolution method for blinded overencapsulated erlotinib tablets using UV fiber optic detection

Cited by 9 publications

References 13 publications

Use of Enzymes in the Dissolution Testing of Gelatin Capsules and Gelatin-Coated Tablets-Revisions to Dissolution <711> and Disintegration and Dissolution of Dietary Supplements <2040>

Use of Enzymes in the Dissolution Testing of Gelatin Capsules and Gelatin-Coated Tablets-Revisions to Dissolution <711> and Disintegration and Dissolution of Dietary Supplements <2040>

Dissolution of Gelatin Capsules: Evidence and Confirmation of Cross-Linking

Density functional methods study on the structures and spectral characteristics for pharmacophoric conformers, metabolites, and combined fragments of Erlotinib

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