Enteric Hard Capsules for Targeting the Small Intestine: Positive Correlation between In Vitro Disintegration and Dissolution Times

Fu, Maoqi; Al-Gousous, Jozef; Blechar, Johannes Andreas; Langguth, Peter

doi:10.3390/pharmaceutics12020123

Cited by 12 publications

(7 citation statements)

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“…The preparation of the caffeine-filled HPMC capsules was described in a previous publication [ 15 ]. Each capsule had a dose of 73.5 ± 4.0 mg of caffeine and passed the content uniformity test (2.9.6.)…”

Section: Methodsmentioning

confidence: 99%

Toward Mechanistic Design of Surrogate Buffers for Dissolution Testing of pH-Dependent Drug Delivery Systems

et al. 2020

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The in vivo dissolution of enteric-coated (EC) products is often overestimated by compendial in vitro dissolution experiments. It is of great interest to mimic the in vivo conditions as closely as possible in vitro in order to predict the in vivo behavior of EC dosage forms. The reason behind this is the overly high buffering capacity of the common compendial buffers compared to the intestinal bicarbonate buffer. However, a bicarbonate-based buffer is technically difficult to handle due to the need for continuous sparging of the media with CO2 to maintain the desired buffer pH. Therefore, bicarbonate buffers are not commonly used in routine practice and a non-volatile alternative is of interest. A mathematical mass transport modelling approach was previously found to enable accurate calculation of surrogate buffer molarities for small molecule compounds; however, the additional complexity of polymeric materials makes this difficult to achieve for an enteric coat. In this work, an approach was developed allowing relatively rapid screening of potential surrogate buffers for enteric coating. It was found that the effective buffering pKa of bicarbonate at the surface of a dissolving enteric polymer tended to be around 5.5, becoming higher when the dissolving enteric polymer formed a gel of greater firmness/viscosity and vice versa. Using succinate (pKa 5.2 under physiological ionic strength) and/or citrate (pKa 5.7 under physiological ionic strength) at conjugate base molarities corresponding to bicarbonate molarities in the intestinal segments of interest as an initial “guess” can minimize the number of experimental iterations necessary to design an appropriate surrogate.

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Section: Methodsmentioning

confidence: 99%

Toward Mechanistic Design of Surrogate Buffers for Dissolution Testing of pH-Dependent Drug Delivery Systems

et al. 2020

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“…Disintegration tests were performed with disks unless otherwise specified. In a previous study a correlation between the disintegration time and dissolution of enteric-coated capsules was found [13]. Therefore, only disintegration tests were performed as surrogate for the drug release from coated capsules.…”

Section: Coating Formulationsmentioning

confidence: 99%

“…Another technique to achieve gastric resistance was described by Smith et al who prepared capsules with bulk enteric properties, thus omitting the need of applying an enteric coating [11]. However, in a recent study by our group DRcaps ® , a commercially available example of capsules with bulk enteric properties [12], was inferior to coated capsules regarding the acid-resistance and showed considerable deformation after 1 h in acidic media [13]. This indicates that it still might be too early for such capsules to obviate the need for enteric coatings.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Evaluation of Enteric-Coated HPMC Capsules—Effect of Formulation Factors on Product Performance

Blechar

Sauer³

et al. 2020

Pharmaceutics

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A comparative study on different enteric-coated hard capsules was performed. The influence of different formulation factors like choice of enteric polymer, triethyl citrate (TEC) concentration (plasticizer), talc concentrations (anti-tacking agent), and different coating process parameters on the sealing performance of the capsule and the disintegration time were investigated. Furthermore, the influence of different disintegration test methods (with disc vs. without disc and 50 mM U.S. Pharmacopoeia (USP) buffer pH 6.8 vs. biopredictive 15 mM phosphate buffer pH 6.5) was evaluated. All formulations showed sufficient but not equivalent acid resistance when tested. Polymer type was the main factor influencing the capsule sealing and disintegration time. In addition, TEC and talc could affect the performance of the formulation. Regarding the choice of the disintegration test method, the presence of a disc had for the most part only limited influence on the results. The choice of disintegration buffer was found to be important in identifying differences between the formulations.

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“…Lennernäs et al thoroughly discuss the predictive ability of rat colon studies in relation to human data and conclude that improved predictability is needed for controlled release formulations, and the use of permeation enhancers to increase colonic permeability could have higher risks than potential rewards [ 38 ]. Langguth's group studied the relevance of dissolution and disintegration of controlled release (CR) dosage forms, obtaining good correlations between the two processes [ 39 ] . This work may have significant regulatory impact, as it opens the way to extend the dissolution-based waiver concept beyond immediate-release dosage forms.…”

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confidence: 99%

“…This work may have significant regulatory impact, as it opens the way to extend the dissolution-based waiver concept beyond immediate-release dosage forms. However, the authors conclude that the extrapolation of these results to the in vivo situation should be done with caution due to additional factors that should be considered, e.g., transporter saturation effects, interplay with food and gastric emptying effects, and different hydrodynamics or mechanical stresses; these factors may complicate the correlation between disintegration and bioavailability [ 39 ]. Dahan's group investigated the role of segmental-dependent intestinal absorption in controlled release (CR) drug product development.…”

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Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation

Dahan

González‐Álvarez

2021

Pharmaceutics

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: The gastrointestinal tract (GIT) can be broadly divided into several regions: the stomach, the small intestine (which is subdivided to duodenum, jejunum, and ileum), and the colon. The conditions and environment in each of these segments, and even within the segment, are dependent on many factors, e.g., the surrounding pH, fluid composition, transporters expression, metabolic enzymes activity, tight junction resistance, different morphology along the GIT, variable intestinal mucosal cell differentiation, changes in drug concentration (in cases of carrier-mediated transport), thickness and types of mucus, and resident microflora. Each of these variables, alone or in combination with others, can fundamentally alter the solubility/dissolution, the intestinal permeability, and the overall absorption of various drugs. This is the underlying mechanistic basis of regional-dependent intestinal drug absorption, which has led to many attempts to deliver drugs to specific regions throughout the GIT, aiming to optimize drug absorption, bioavailability, pharmacokinetics, and/or pharmacodynamics. In this Editorial we provide an overview of the Special Issue "Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation". The objective of this Special Issue is to highlight the current progress and to provide an overview of the latest developments in the field of regional-dependent intestinal drug absorption and delivery, as well as pointing out the unmet needs of the field.

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Enteric Hard Capsules for Targeting the Small Intestine: Positive Correlation between In Vitro Disintegration and Dissolution Times

Cited by 12 publications

References 11 publications

Toward Mechanistic Design of Surrogate Buffers for Dissolution Testing of pH-Dependent Drug Delivery Systems

Toward Mechanistic Design of Surrogate Buffers for Dissolution Testing of pH-Dependent Drug Delivery Systems

In Vitro Evaluation of Enteric-Coated HPMC Capsules—Effect of Formulation Factors on Product Performance

Regional Intestinal Drug Absorption: Biopharmaceutics and Drug Formulation

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