aQbD as a platform for IVRT method development – A regulatory oriented approach

Miranda, Margarida; Pais, Alberto A. C. C.; Cardoso, Catarina

doi:10.1016/j.ijpharm.2019.118695

Cited by 22 publications

(31 citation statements)

References 40 publications

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“…The solubility was then assessed in the following conditions: PBS/co-solvent 80:20 and 70:30, v/v. On the other hand, diclofenac solubility is impacted by the pH, consequently, screening studies were performed at a pH values of 3.6, 5.5, and 7.4 in the condition PBS/co-solvent 80:20, v/v [11].…”

Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

“…Ethanol was herein selected due to its prevalence in the literature, while the selection of propylene glycol was mainly related to the presence of this component in the qualitative formulation of some products. In fact, among the polyvalent alcohols, propylene glycol is the most frequently used co-solvent in topical products [11,38]. Nevertheless, for all drugs, ethanol demonstrated a higher solubility.…”

Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

“…Finally, for diclofenac, a PBS/ethanol 80:20, v/v, at a pH = 7.4 was selected. Please note that diclofenac conditions were already optimized in a previous study directed at IVRT method optimization [11]. Ethanol was herein selected due to its prevalence in the literature, while the selection of propylene glycol was mainly related to the presence of this component in the qualitative formulation of some products.…”

Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

“…The European Medicine Agency (EMA) guideline on quality and equivalence of topical products as well as the US Food and Drug Administration's (FDA) acyclovir draft guidance are clear regulatory examples, which reinforce the growing need to fully characterize topical products [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…To standardize method conditions, release experiments should be temperature controlled and continuously stirred. This avoids the occurrence of stationary layers that limit drug diffusion and prevent homogenization of the drug within the receptor solution [11,[17][18][19]. Moreover, prior to the release experiment, it is vital to perform solubility studies to assure the maintenance of sink conditions.…”

Section: Introductionmentioning

confidence: 99%

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Fast Screening Methods for the Analysis of Topical Drug Products

Miranda

Cardoso²,

Vitorino

2020

Processes

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Considering the recent regulatory requirements, the overall importance of in vitro release testing (IVRT) methods regarding topical product development is undeniable, especially when addressing particulate systems. For each IVRT study, several hundreds of samples are generated. Therefore, developing rapid reversed-phase high-performance liquid chromatography (RP-HPLC) methods, able to provide a real-time drug analysis of IVRT samples, is a priority. In this study, eight topical complex drug products exhibiting distinct physicochemical profiles were considered. RP-HPLC methods were developed and fully validated. Chromatographic separations were achieved on a XBridgeTM C18 (5 µm particle size, 150 mm × 2.1 mm), or alternatively on a LiChrospher® 100 RP-18 (5 µm particle size, 125 mm × 4.6 mm) at 30 °C, under isocratic conditions using UV detection at specific wavelengths. According to the physicochemical characteristics of each drug, different mobile phases were selected. Irrespective of the drug (hydrocortisone, etofenamate, bifonazole, clotrimazole, acyclovir, tioconazole, clobetasol, and diclofenac) and formulation, retention time values did not exceed 6.5 min. All methods were linear, specific, precise, and accurate at the intraday and interday levels, robust, and stable. These were successfully applied to establish product-specific IVRT profiles, thus providing a key database useful for topical pharmaceutical manufacturers.

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Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

Section: In Silico Studies: Using Chemical Predictors To Support Ivrtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fast Screening Methods for the Analysis of Topical Drug Products

Miranda

Cardoso²,

Vitorino

2020

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Diving into Batch-to-Batch Variability of Topical Products-a Regulatory Bottleneck

Miranda

Cova

Augusto³

et al. 2020

Pharm Res

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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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aQbD as a platform for IVRT method development – A regulatory oriented approach

Cited by 22 publications

References 40 publications

Fast Screening Methods for the Analysis of Topical Drug Products

Fast Screening Methods for the Analysis of Topical Drug Products

Diving into Batch-to-Batch Variability of Topical Products-a Regulatory Bottleneck

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

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