Sink conditions in the flow-through cell during dissolution

Posti, Juhani; Speiser, P

doi:10.1016/0378-5173(80)90014-9

Cited by 15 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The latter method is therefore particularly applicable for the testing of low solubility compounds, where large media volumes are required [48] . Importantly, when in the open‐loop configuration, analyte solubility can be increased without the addition of surfactants or other solvents to the dissolution medium [45,49] . The system also bears some resemblance to the physiological environment of the gastrointestinal tract by continuously extracting drug from the dissolution vessel, thus mimicking absorption into the systemic circulation [50] .…”

Section: Methods For Maintaining Dissolution Sink Conditionsmentioning

confidence: 99%

“…[48] Importantly, when in the open-loop configuration, analyte solubility can be increased without the addition of surfactants or other solvents to the dissolution medium. [45,49] The system also bears some resemblance to the physiological environment of the gastrointestinal tract by continuously extracting drug from the dissolution vessel, thus mimicking absorption into the systemic circulation. [50] However, this technique is not without its disadvantages: the potential for plugging/blockages to occur within the set-up of the apparatus, especially when biorelevant media are used, or when significant experiment times are required, has been discussed elsewhere.…”

Section: Co-solventsmentioning

confidence: 99%

See 1 more Smart Citation

Overcoming sink limitations in dissolution testing: a review of traditional methods and the potential utility of biphasic systems

Phillips

Pygall²,

Cooper³

et al. 2012

Journal of Pharmacy and Pharmacology

168

109

View full text Add to dashboard Cite

Objectives The conventional dissolution test, particularly the USP apparatus I and II, remains an important tool in the armory of the pharmaceutical development scientist. For realistic dissolution characterization, sink conditions, where saturation solubility of a drug in the dissolution medium is at least three times more than the drug concentration, are critical. These conditions can be problematic to maintain with formulations containing poorly-soluble actives. This review summarizes the role of the dissolution test in the pharmaceutical industry, together with some traditional techniques/additives used to enhance solubility and facilitate the achievement of sink conditions. The biphasic dissolution system, an innovative model for the treatment of poorly-soluble species, will also be discussed. Key findings The biphasic dissolution model utilizes media comprising immiscible aqueous and organic layers whereby the drug, following initial aqueous dissolution, partitions into the organic layer. This step, which acts to remove all dissolved species from the aqueous layer, enables further aqueous dissolution to occur and hence the dissolution-partition cycle continues. Crucially, the aqueous layer does not saturate allowing sink conditions to be maintained and hence the experiment will, in theory, yield complete dissolution. Summary This review highlights important concepts regarding solubility/sink limitation and intends to provoke debate among analytical and formulation scientists as to the potential advantages, long-term development and widespread implementation of a biphasic dissolution system in drug development.

show abstract

Section: Methods For Maintaining Dissolution Sink Conditionsmentioning

confidence: 99%

Section: Co-solventsmentioning

confidence: 99%

Overcoming sink limitations in dissolution testing: a review of traditional methods and the potential utility of biphasic systems

Phillips

Pygall²,

Cooper³

et al. 2012

Journal of Pharmacy and Pharmacology

168

109

View full text Add to dashboard Cite

show abstract

“…Local conditions can cause saturation to occur as reported by Posti (15). Samples of acetaminophen (paracetamol) particles were subjected to dissolution commingled with glass beads in the 22.6-mm flow-through cell.…”

Section: Small Hold-up Volumementioning

confidence: 99%

Apparatus 4 Flow Through Cell: Some Thoughts on Operational Characteristics

Brown¹

2005

Dissolution Technol.

View full text Add to dashboard Cite

“…[5][6][7] The conventional single-phase dissolution experiments are "generally" run under nonsink conditions and, thus, do not capture the permeation process. 8,9 A number of techniques have been employed to achieve sink or near sink conditions viz. (1) increasing the dissolution media volume (typically up to 900-1000 mL in USP I and II apparatus), (2) addition of solubility enhancers such as surfactants, 10 (3) continuous media change flow through cell (USP IV) apparatus, [11][12][13] (4) integrating sink dialysis bag, or (5) use of an additional (organic) phase into which drug can partition.…”

Section: Introductionmentioning

confidence: 99%

Biopharmaceutic IVIVE—Mechanistic Modeling of Single- and Two-Phase In Vitro Experiments to Obtain Drug-Specific Parameters for Incorporation Into PBPK Models

Pathak

Schaefer

Jamei

et al. 2019

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The physiological relevance of single-phase (aqueous only) and 2-phase (aqueous and organic phase) in vitro dissolution experiments was compared by mechanistic modeling. For orally dosed dipyridamole, stepwise, sequential estimation/confirmation of biopharmaceutical parameters from in vitro solubilitydissolution data was followed, before applying them within a physiologically based pharmacokinetic (PBPK) model. The PBPK model predicted clinical dipyridamole luminal and plasma concentration profiles reasonably well for a range of doses only where the precipitation rate constant was derived from the 2-phase experiment. The population model predicted a distribution of maximal precipitated fractions from 0% to 45% of the 90 mg dose (mean 7.6%). Such population information cannot be obtained directly from a few in vitro experiments; however well they may represent an "average" and several extreme subjects (those with low-high luminal fluid volumes, pH, etc.) because there is no indication of outcome likelihood. For this purpose, direct input of in vitro dissolution/precipitation profiles to a PBPK model is insufficientdmechanistic modeling is required. Biopharmaceutical in vitro-in vivo extrapolation tools can also simulate the effect of key experimental parameters (dissolution volumes, pH, paddle speed, etc.) on dissolution/precipitation behavior, thereby helping to identify critical variables, which may impact the number or design of in vitro experiments.

show abstract

Sink conditions in the flow-through cell during dissolution

Cited by 15 publications

References 9 publications

Overcoming sink limitations in dissolution testing: a review of traditional methods and the potential utility of biphasic systems

Overcoming sink limitations in dissolution testing: a review of traditional methods and the potential utility of biphasic systems

Apparatus 4 Flow Through Cell: Some Thoughts on Operational Characteristics

Biopharmaceutic IVIVE—Mechanistic Modeling of Single- and Two-Phase In Vitro Experiments to Obtain Drug-Specific Parameters for Incorporation Into PBPK Models

Contact Info

Product

Resources

About