Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review

Todaro, Valério; Pearsons, Tim; Grove, Geoffrey N.; Healy, Anne Marie; D’Arcy, Deirdre M.

doi:10.14227/dt240317p24

Cited by 36 publications

(20 citation statements)

References 50 publications

(109 reference statements)

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“…The purpose of this work was a rationale development of a fully automated, small-scale, one-vessel biphasic dissolution method, which generates biorelevant results, for the fasted state using a hot-melt extruded ritonavir-containing amorphous solid dispersion formulation (ritonavir-ASD). Thus, the most relevant geometrical parameters have been identified [17], which are necessary for scaling down at controlled hydrodynamics [18,19]. Emphasis was put on the development of biorelevant aqueous media suitable to keep buffer capacity constant over the entire pH range.…”

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confidence: 99%

A Rational Design of a Biphasic Dissolution Setup—Modelling of Biorelevant Kinetics for a Ritonavir Hot-Melt Extruded Amorphous Solid Dispersion

et al. 2020

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Biphasic dissolution systems achieved good predictability for the in vivo performance of several formulations of poorly water-soluble drugs by characterizing dissolution, precipitation, re-dissolution, and absorption. To achieve a high degree of predictive performance, acceptor media, aqueous phase composition, and the apparatus type have to be carefully selected. Hence, a combination of 1-decanol and an optimized buffer system are proposed as a new, one-vessel biphasic dissolution method (BiPHa+). The BiPHa+ was developed to combine the advantages of the well-described biorelevance of the United States Pharmacopeia (USP) apparatus II coupled with USP apparatus IV and a small-scale, one-vessel method. The BiPHa+ was designed for automated medium addition and pH control of the aqueous phase. In combination with the diode array UV-spectrophotometer, the system was able to determine the aqueous and the organic medium simultaneously, even if scattering or overlapping of spectra occurred. At controlled hydrodynamic conditions, the relative absorption area, the ratio between the organic and aqueous phase, and the selected drug concentrations were identified to be the discriminating factors. The performance of a hot-melt extruded ritonavir-containing amorphous solid dispersion (ritonavir-ASD) was compared in fasted-state dissolution media leading to different dissolution-partitioning profiles depending on the content of bile salts. An advanced kinetic model for ASD-based well described all phenomena from dispersing of the ASD to the partitioning of the dissolved ritonavir into the organic phase.

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A Rational Design of a Biphasic Dissolution Setup—Modelling of Biorelevant Kinetics for a Ritonavir Hot-Melt Extruded Amorphous Solid Dispersion

et al. 2020

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“…Differences between both USP apparatuses were expected owing to the different hydrodynamics of each apparatus; however, it is necessary to understand at what agitation rate this difference is more evident. Despite the wide use of USP Apparatuses 1 and 2 at different agitation rates, they have still been evaluated by several authors in terms of the surrounding hydrodynamic environments, which do not adequately reproduce the natural environment of the gastrointestinal tract [13][14][15]32,40].…”

Section: Discussionmentioning

confidence: 99%

“…Low solubility and permeability are problematic characteristics of class IV drugs; thus, the determination of in vitro release performance using different agitation rates, dissolution media, and dissolution apparatuses provides important information for improving the manufacture and evaluation of generic formulations. Despite the wide use of USP basket and paddle apparatuses (USP Apparatus 1 and 2, respectively) to monitor the physical quality of tablets and capsules, several investigations about the hydrodynamic environment that surrounds oral formulations have reported that these USP apparatuses do not adequately reproduce the natural environment of the gastrointestinal tract [13][14][15]; thus, it is necessary to document the in vitro release performance of poorly soluble drugs under different conditions to establish, in the best possible way, the environment in which the solid dosage forms will be within the gastrointestinal tract. Further, alternative apparatuses must be developed to achieve this goal.…”

Section: Introductionmentioning

confidence: 99%

In vitro release studies of furosemide reference tablets: influence of agitation rate, USP apparatus and dissolution media

López¹,

Guillén-Moedano²,

Hurtado³

2020

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<p class="ADMETabstracttext">Furosemide is a diuretic drug widely used in chronic renal failure. The drug has low solubility and permeability, which cause clinical problems. Studying the in vitro release performance elucidates the rate and extent of drug dissolved from dosage forms under different conditions. Furosemide reference tablets were tested using USP Apparatuses 1 and 2 as well as the flow-through cell method (USP Apparatus 4), a dissolution apparatus that simulates the human gastrointestinal tract better than the other methods. Dissolution profiles were created with USP Apparatuses 1 and 2 at 25, 50, and 75 rpm and 900 mL of 0.1 M hydrochloric acid, acetate buffer (pH 4.5), and phosphate buffer (pH 6.8). USP Apparatus 4 with a laminar flow of 16 mL/min and 22.6 mm cells was used. Drug dissolution was quantified at 274 nm for 60 min. Mean dissolution time, dissolution efficiency, time to 50 % dissolution, and time to 80 % dissolution data were used to compare dissolution profiles. Additionally, zero-order, first-order, Higuchi, Hixson-Crowell, Makoid-Banakar, and Weibull models were used to adjust furosemide dissolution data. Between USP Apparatus 1 and 2, significant differences were observed in almost all parameters at 50 and 75 rpm (p < 0.05). A similar dissolution profile (f<sub>2</sub> > 50) with a pharmacopoeial dissolution method (USP Apparatus 2 at 50 rpm and 900 mL of phosphate buffer pH 5.8) and USP Apparatus 4 (laminar flow of 16 mL/min, 22.6 mm cells, and pH 6.8) was observed. The Weibull function was the best mathematical model to describe the in vitro release performance of furosemide in the three USP dissolution apparatuses. These results could be used to manufacture better furosemide dosage forms and decrease the negative clinical impact of current furosemide formulations.</p>

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“…In the exploratory method used in the study, the sensitivity in discriminating dosage forms was seen in the octanol phase when applying 200 mL of the aqueous phase, whereas at 900 mL the differences were more pronounced in the aqueous phase. The low surface area to volume ratio at 900 mL and the hydrodynamics in the vessel with a paddle dissolution apparatus resulted in slower drug partitioning (drug removal) compared to at 200 mL ( Figure 4 A,B vs. Figure 4 C) [ 38 , 39 , 40 ]. Consequently, in 900 mL partitioning is the rate-limiting step for the overall process of mass transfer between the solid, the aqueous and the octanol phases.…”

Section: Discussionmentioning

confidence: 99%

Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

et al. 2020

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Dissolution testing is a major tool used to assess a drug product’s performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance.

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Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review

Cited by 36 publications

References 50 publications

A Rational Design of a Biphasic Dissolution Setup—Modelling of Biorelevant Kinetics for a Ritonavir Hot-Melt Extruded Amorphous Solid Dispersion

A Rational Design of a Biphasic Dissolution Setup—Modelling of Biorelevant Kinetics for a Ritonavir Hot-Melt Extruded Amorphous Solid Dispersion

In vitro release studies of furosemide reference tablets: influence of agitation rate, USP apparatus and dissolution media

Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

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