Dissolution Testing in Drug Product Development: Workshop Summary Report

Abend, Andreas; Curran, David; Kuiper, Jesse; Lu, Xujin; Li, Hanlin; Hermans, Andre; Kotwal, Pramod; Diaz, Dorys Argelia; Cohen, Michael J.; Zhang, Limin; Stippler, Erika; Drazer, Germán; Lin, Yiqing; Raines, Kimberly; Yu, Lawrence X.; Coutant, Carrie A.; Grady, Haiyan; Krämer, Johannes; Pope-Miksinski, Sarah; Suarez-Sharp, Sandra

doi:10.1208/s12248-018-0288-4

Cited by 24 publications

(16 citation statements)

References 13 publications

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“…Thus, in the absence of a link to in vivo drug product performance, the degree of discriminating power is often unknown. In such cases, risk assessments and prior knowledge, as well as modeling and simulation, may be helpful to guide the necessary adjustments to increase the method's sensitivity towards certain critical API attributes, manufacturing method, and/or formulation composition [2,25].…”

Section: Discussionmentioning

confidence: 99%

“…The test was developed in the late 1950s/early 1960s and accepted by the United States Pharmacopeia (USP) convention in 1970 [1]. Ever since, in vitro dissolution testing has been used as a quality control (QC) test for solid oral dosage forms and it plays a critical role in enhanced product understanding [2]. The different compendial dissolution equipment includes the basket (USP apparatus 1), the paddle (USP apparatus 2), the reciprocating cylinder (USP apparatus 3), and the flow-through cell (USP apparatus 4).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the quality control aspects of the dissolution methodologies are mostly meaningful in a commercial environment of finished drug product release. Nevertheless, during the drug product development process, in vivo predictive methods are needed for the creation of products of predictable quality [2]. In this realm, dissolution testing is a major tool used to asses a drug product's performance.…”

Section: Introductionmentioning

confidence: 99%

“…As suggested by Azarmi et al, two different dissolution methods might be needed, one for formulation predictive dissolution and the other for QC purposes, which is the current practice in pharmaceutical companies [2,19]. The information obtained from early stage dissolution methods (exploratory and physiologically based) can be then used to establish appropriate discrimination of the QC method to be applied in the late development stage to critical dosage form attributes and other parameters ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

et al. 2020

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“…For sustained/controlled release dosage forms such as vaginal rings, methods typically involve sampling at multiple time points extending over the same time period as intended for clinical use [4,5,7]. In early-stage product development, IVRT can be useful in differentiating between formulations and helping determine critical material attributes, process parameters, and quality attributes of the intended product [8]. In the later stages of development, IVRT is used to set specifications for batch release, determine batch-to-batch variability, and potentially investigate product differences through changes in formulation or manufacturing [8].…”

Section: Introductionmentioning

confidence: 99%

Refining the in vitro release test method for a dapivirine-releasing vaginal ring to match in vivo performance

Murphy

Lim

Armstrong

et al. 2021

Drug Deliv. and Transl. Res.

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Previously reported in vitro release test methods for drug-releasing vaginal rings containing poorly water-soluble drugs have described use of water-alcohol systems or surfactant solutions in efforts to maintain sink conditions. Here, as part of efforts to more closely match in vitro and in vivo release for the 25 mg dapivirine matrix-type silicone elastomer vaginal ring for HIV prevention, we have investigated alternatives to the 1:1 v/v water/isopropanol medium described previously. Specifically, we evaluated dapivirine release from rings into (i) monophasic water/isopropanol mixtures of varying compositions and (ii) biphasic buffer/octanol systems using pH 4.2 and pH 7.0 buffers. The rate and mechanism of dapivirine release were dependent upon the isopropanol concentration in the release medium, in accordance with the observed trend in drug solubility. At 0 and 10% v/v isopropanol concentrations, dapivirine release followed a partition-controlled mechansim. For media containing ≥ 20% v/v isopropanol, in vitro release of dapivirine was significantly increased and obeyed permeation-controlled kinetics. Cumulative release of ~3.5 mg dapivirine over 28 days was obtained using a water isopropanol mixture containing 20% v/v isopropanol, similar to the ~4 mg dapivirine released in vivo. Dapivirine release into the biphasic buffer/octanol system (intended to mimic the fluid/tissue environment in vivo) was constrained by the limited solubility of dapivirine in the buffer component in which the ring resided, such that cumulative dapivirine release was consistently lower than that observed with the 20% v/v isopropanol in water medium. Release into the biphasic system was also pH dependent, in line with dapivirine’s pKa and with potential implications for in vivo release and absorption in women with elevated vaginal pH. Graphical abstract

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White paper: Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin

Dul,

Alali,

Ameri

et al. 2025

Journal of Controlled Release

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Dissolution Testing in Drug Product Development: Workshop Summary Report

Cited by 24 publications

References 13 publications

Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

Biphasic Dissolution as an Exploratory Method during Early Drug Product Development

Refining the in vitro release test method for a dapivirine-releasing vaginal ring to match in vivo performance

White paper: Understanding, informing and defining the regulatory science of microneedle-based dosage forms that are applied to the skin

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