Can the USP paddle method be used to represent in-vivo hydrodynamics?

Scholz, Annette; Kostewicz, Edmund; Abrahamsson, Bertil; Dressman, Jennifer B.

doi:10.1211/002235702946

Cited by 54 publications

(32 citation statements)

References 47 publications

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“…1) is widely used for the study of in vitro drug release mechanisms [24]. An advantage of this model is that parameter calculation is independent of whether or not sink conditions prevail [25]. As the generic product B and reference were well adjusted to this function, β parameter was used to compare the dissolution profiles.…”

Section: Model-dependent Comparisonsmentioning

confidence: 99%

Comparison of the Usp Apparatus 2 and 4 for Testing the in Vitro Release Performance of Ibuprofen Generic Suspensions

2017

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Objective: The aim of this study was the comparison of the in vitro release performance of ibuprofen generic suspensions and reference, based on the hydrodynamic environment generated by the flow-through cell method (USP Apparatus 4). Results were compared with those obtained by the use of the USP Apparatus 2. Methods:The Advil ® suspension (2 g/100 ml) and two generic formulations with the same dose were tested. Dissolution studies were carried out using a USP Apparatus 4 Sotax CE6 with 22.6 mm cells, laminar flow at 16 ml/min, and pH 7.2 phosphate buffer at 37.0±0.5 °C as dissolution medium. Ibuprofen was quantified spectrophotometrically at 222 nm. The in vitro release of the three drug products were studied using the USP Apparatus 2. The dissolution profiles of generic products were compared with the reference by model-independent, model-dependent, and analysis of variance (ANOVA)-based comparisons. Results:The dissolution profile of the generic product A was similar to the dissolution profile of reference, only with the use of the USP Apparatus 4. The f2 similarity factor was>50 and no significant differences were found with dissolution efficiency data (*P>0.05). Similar results were found with the comparison of t50% and t63.2% values. Similar dissolution profiles between generic product A and reference were also found with ANOVAbased comparisons. Conclusion:The flow-through cell method was adequate for study the in vitro release of ibuprofen suspensions. It is necessary to evaluate the in vivo performance of the drug products used in order to estimate the predictability of the proposed methodology.

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Section: Model-dependent Comparisonsmentioning

confidence: 99%

Comparison of the Usp Apparatus 2 and 4 for Testing the in Vitro Release Performance of Ibuprofen Generic Suspensions

2017

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“…After administration, the SL tablet is maintained in a relatively quiescent environment under the tongue as simulated in this apparatus. The lack of agitation of dissolution medium in our apparatus eliminates the problem of unstable hydrodynamics of small-volume dissolution apparatus, which is a major concern with USP Basket or Paddle apparatuses (14,(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Dissolution Testing of Sublingual Tablets: A Novel In Vitro Method

et al. 2011

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Abstract. In the sublingual (SL) cavity, compared with the gastrointestinal tract, tablets are subjected to minimal physiological agitation, and a limited volume of saliva is available to facilitate disintegration and dissolution. None of the official compendial dissolution apparatuses and methods simulate these SL conditions. In this study, a custom-made dissolution apparatus was constructed, and a novel in vitro method that simulates SL conditions was evaluated. Several epinephrine 40 mg SL tablet formulations under development and two commercial SL tablets, isosorbide dinitrate 5 mg and nitroglycerin 0.6 mg, were studied. The dissolution medium was 2 mL of distilled water at 25°C. Dissolution was measured at 60 and 120 s. The novel in vitro method was validated for accuracy, reproducibility, and discrimination capability, and was compared with the official US Pharmacopeia (USP) dissolution method using apparatus 2 (Paddle). The data obtained following the novel in vitro method were accurate and reproducible. This method was capable of detecting minor changes in SL formulations that could not be detected using other in vitro tests. Results from the official USP dissolution method and our novel in vitro method were significantly different (p<0.05). Results reflecting the dissolution of rapidly disintegrating tablets using simulated SL conditions were obtained using the novel in vitro dissolution method.

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“…Fhsuspension and Fhsolution can be calculated by equations (10) and (11). Where AUC0-∞ , suspension, pv, AUC0-∞ , suspension, sys, AUC0-∞, solution, pv and AUC0-∞, solution, sys are the AUC at time 0 h-infinity in the portal vein and systemic circulation after oral administration of GF suspension and solution, respectively.…”

Section: Calculation Of the In Vivo Famentioning

confidence: 99%

“…Where AUC0-∞ , suspension, pv, AUC0-∞ , suspension, sys, AUC0-∞, solution, pv and AUC0-∞, solution, sys are the AUC at time 0 h-infinity in the portal vein and systemic circulation after oral administration of GF suspension and solution, respectively. Fhsuspension/Fhsolution were estimated using equations (10) and (11). (12) Qpv and Rb were assumed to be the same value in the administrations of both GF suspension and solution.…”

Section: Calculation Of the In Vivo Famentioning

confidence: 99%

Prediction of Oral Absorption of Low-Solubility Drugs by Using Rat Simulated Gastrointestinal Fluids: The Importance of Regional Differences in Membrane Permeability and Solubility

et al. 2014

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-Purpose. This study aimed to develop a novel approach for predicting the oral absorption of low-solubility drugs by considering regional differences in solubility and permeability within the gastrointestinal (GI) tract. Methods. Simulated GI fluids were prepared to reflect rat in vivo bile acid and phospholipid concentrations in the upper and lower small intestine. The saturated solubility and permeability of griseofulvin (GF) and albendazole (AZ), a drug with low aqueous solubility, were measured using these simulated fluids, and fraction absorbed (Fa) at time t after oral administration was calculated. Results. The saturated solubility of GF and AZ, a drug with low aqueous solubility, differed considerably between the simulated GI fluids. Large regional differences in drugs concentration were also observed following oral administration in vivo. The predicted Fa values using solubility and permeability data of the simulated GI fluid were found to correspond closely to the in vivo data. Conclusion. These results indicated the importance of evaluating regional differences in drug solubility and permeability in order to predict oral absorption of low-solubility drugs accurately. The new methodology developed in the present study could be useful for new oral drug development.

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Can the USP paddle method be used to represent in-vivo hydrodynamics?

Cited by 54 publications

References 47 publications

Comparison of the Usp Apparatus 2 and 4 for Testing the in Vitro Release Performance of Ibuprofen Generic Suspensions

Comparison of the Usp Apparatus 2 and 4 for Testing the in Vitro Release Performance of Ibuprofen Generic Suspensions

Dissolution Testing of Sublingual Tablets: A Novel In Vitro Method

Prediction of Oral Absorption of Low-Solubility Drugs by Using Rat Simulated Gastrointestinal Fluids: The Importance of Regional Differences in Membrane Permeability and Solubility

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