Advances in In Vivo Predictive Dissolution Testing of Solid Oral Formulations: How Closer to In Vivo Performance?

Shrivas, Meera; Khunt, Dignesh; Shrivas, Meenakshee; Choudhari, Manisha; Rathod, Rajeshwari; Misra, Manju

doi:10.1007/s12247-019-09392-6

Cited by 14 publications

(7 citation statements)

References 130 publications

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“…Some generalizations about dissolution and permeation characteristics In vivo can be made based on relative solubilities, as well as on permeability along the intestine, characteristics of drug substances, which can be used as a resuming point for development of an In vivo biopredictive dissolution methodology (IPD) and IVIVC technique. These predictions are obtained using software which involves physiologically based pharmacokinetic models describing drug concentration in tissues using physicochemical data of the drugs as well as other data [15,16].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction

Pawar¹,

Jagdale

2021

JPRI

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Aim: This research work was aimed to evaluate Metformin hydrochloride (MH) floating dosage form by In vitro evaluation/In vivo prediction and to evaluate it’s predictability through it’s application during the R&D using Insilico technique in WINONLIN Software. MH was examined as a model drug, which is a biguanide and is an hypoglycemic agent administered orally. The study was aimed to determine the the systemic concentrations of MH using In-vivo prediction. Study Design: Fabrication and assessment of Metformin hydrochloride floating drug delivery system: In Vitro evaluation /In Vivo prediction. Biorelevant media was selected for dissolution profile of 12 units of dosage form. Software assisted program used for data feeding and results output. Methodology: The absorption window for MH is the upper portion of the small gut in which the GI absorption is complete after 6 h. Hence gastroretentive formulation was developed and validity of dissolution study was extended by In vivo pharmacokinetic prediction using WinNonlin Software. A mechanistic oral absorption model was built in Phoenix WinNonlin® software. In the presented work, significant yet crucial, gastrointestinal (GI) variables are considered for biopredictive dissolution testing to account for a valuable input for physiologically-based pharmacokinetic (PBPK) platform programs. While simulations are performed and mechanistic insights are gained from such simulations from the WinNonlin program. Results: These floating tablets were observed for In vitro release and studied for In vivo pharmacokinetic prediction. From the obtained values, a meaningful In vivo prediction was done. interestingly from the results attained floating tablets showed sustained drug release and extended drug absorbed in 24h. Fascinatingly, from the data it was proved that drug formulation resides for desired time. The absorption of MH from the developed CR tablet was 1.4 fold higher than its marketed tablet and it had higher AUC0–t values than the marketed product which indicates superior bioavailability of test product compared to marketed tablet with similar dose in Invivo pharmacokinetic prediction. The mean value of biological half-life (t1/2) and Tmax of MH from test formulation is two times more, Test product has shown higher MRT, showing that the drug is maintained longer in the body in comparison to marketed product indicates controlled absorption. Conclusion: Here we concluded that, a comparative prediction pharmacokinetic evaluation of the fabricated controlled release tablets and the marketed formulation indicates that the fabricated controlled release tablets are well absorbed and the degree of absorption is greater than that of the marketed ER formulation with larger gastric residence time.

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Section: Methodsmentioning

confidence: 99%

Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction

Pawar¹,

Jagdale

2021

JPRI

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“…Philosophically there have been two camps on how to resolve the issue. On one side people have been trying to modify the in vitro testing systems and bring what they have coined as "in vivo predictive dissolution tests" via various modifications to the testing system to mimic some aspects of the physiology (see Shrivas et al, 2020 for a recent review). However, others have been promoting the incorporation of the GI system attributes into the physiologically based pharmacokinetic (PBPK) models such that disproportionate changes in the features of the concentration-time profile with changes in dissolution could be defined (Mistry et al, 2016).…”

Section: Current Scientific Considerations For Supporting Bcs III Drug Waiver and Modeling Bcs Iii Drug Absorptionmentioning

confidence: 99%

Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help

Cristofoletti

Zhao

et al. 2021

Biopharm & Drug Disp

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The 2017 Guidance by U.S. Food and Drug Administration (FDA) has recommended the criteria to qualify for a Biopharmaceutical Classification System (BCS)-based biowaiver that includes high solubility of the drug across the physiological pH range as well as the formulation considerations, e.g., being qualitatively the same and quantitatively very similar to the reference product. These were ratified by the International Council for Harmonization (ICH) in 2018. The FDA has used the similar verbiage when referring to the BCS-based biowaiver option for BCS class III drugs (highly soluble but poorly permeable). However, establishing in vitro-in vivo correlations (IVIVC) using conventional mass balance deconvolution approaches, which assumes a single absorption compartment, is not likely for very rapidly dissolving dosage forms containing BCS III drugs. Unlike conventional mass balance deconvolution techniques, physiologically based pharmacokinetic models are able to disentangle different processes contributing to the input function, e.g., dissolution, gastrointestinal transit, and permeation and to establish IVIVC using variants of the compartmental absorption and transit model, supporting biowaiver for formulations containing BCS III drugs. However, there are knowledge gaps that need to be filled.This review provides a systematic assessment of the advancements in applications of physiologically based pharmacokinetic (PBPK) models for IVIVC and biowaiver for such cases with the aim of identifying the most important gaps and hurdles. It concludes by calling for research efforts on the impact of excipients on dissolution and permeation, alongside the development of PBPK modeling to link these in vitro characteristics to in vivo bioequivalence outcomes through simulations of virtual clinical studies

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“…With different excipient formulations and/or operating conditions, important mechanisms, such as disintegration and dissolution in physiological fluids, may be affected. During drug product development and manufacturing, in vitro dissolution testing plays an important role to characterize drug release profile 1 . For example, in vitro dissolution testing is used routinely for batch release testing to detect target product profiles (TPPs) or critical quality attributes (CQAs) changes that affect in vivo release of the drug product.…”

Section: Introductionmentioning

confidence: 99%

Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

Hermant

Casati

et al. 2023

AIChE Journal

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A predictive mathematical model for tablet dissolution was developed and implemented in an end‐to‐end integrated continuous manufacturing pilot plant. The tablets were produced for immediate release with a proprietary extrusion‐molding‐coating (EMC) unit operation. Besides the mass balance of API solute in the buffer solution, the model consisted of the dissolution, diffusion, and population balance of API particles in the swollen tablet, which was mainly controlled by the swelling and erosion of the polymeric excipient matrix. An equivalence study was investigated by comparing the model prediction to the experiments that were conducted according to USP42‐NF37 General Chapter <711> Dissolution, during which the drug dose level was varied in a range from 60 to 80 wt%. Consistent equivalence was demonstrated with the similarity factor f2 > 50 for all sampled tablets. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.

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Advances in In Vivo Predictive Dissolution Testing of Solid Oral Formulations: How Closer to In Vivo Performance?

Cited by 14 publications

References 130 publications

Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction

Evaluation of Metformin Hydrochloride Floating Drug Delivery System: In vitro Study and In vivo Prediction

Scientific considerations to move towards biowaiver for biopharmaceutical classification system class III drugs: How modeling and simulation can help

Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

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