In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Al-Tabakha, Moawia M.; Alomar, Muaed Jamal

doi:10.3390/pharmaceutics12010045

Cited by 21 publications

(18 citation statements)

References 71 publications

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“…The critical quality attributes like FLT was less than 3 minutes and TFT was more than 24 hrs for developed formulation. 4,5,6 Marketed tablets of MH ER formulation viz Carbophage XR tablets 500mg, Lot No. N22AE19032, Mfg by Merck Specialities, Pvt Ltd, India was used for the study.…”

Section: Methodsmentioning

confidence: 99%

“…All this work refers to the fact that important, yet crucial, gastrointestinal (GI) variables should be integrated into biopredictive dissolution testing (low buffer capacity media, considering phosphate versus bicarbonate buffer, hydrodynamics) and it signifies to account for a valuable input for physiologically-based pharmacokinetic platform programs. This PBPK software tool is capable of consistently predicting the in vivo performance of formulations and rationalize product development [5]. In silico mathematical modeling and simulation represents a substantial part of the research and development in pharmaceutical industry aiming to optimize the design of dosage forms.…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Introductionmentioning

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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“…Another way to explore M & S is to assess the relationship between the in vitro and in vivo data (in vitro-in vivo correlation/relationship, IVIVC/IVIVR) so that in vitro dissolution test can be used to identify drug/formulation factors which may affect the bioperformance of a drug product (47)(48)(49). Such an approach can also be used to justify biowaivers i.e., the substitution of the in vivo bioequivalence studies with the relevant in vitro dissolution data (50)(51)(52).…”

Section: Application Of Pbpk/pbbm Modeling In Formulation Developmentmentioning

confidence: 99%

The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development

Cvijić¹,

Ignjatović²,

Parojčić³

et al. 2021

Arhiv za farmaciju

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Computer-based (in silico) modeling & simulation tools have been embraced in different fields of pharmaceutics for a variety of applications. Among these, physiologically-based pharmacokinetic/biopharmaceutics modeling (PBPK/PBBM) emerged as a particularly useful tool in formulation development. PBPK/PBBM facilitated strategies have been increasingly evaluated over the past few years, as demonstrated by several reports from the pharmaceutical industry, and a number of research and review papers on this subject. Also, the leading regulatory authorities have recently issued guidance on the use of PBPK modeling in formulation design. In silico PBPK models can comprise different dosing routes (oral, intraoral, parenteral, inhalation, ocular, dermal etc.), although the majority of published examples refer to modeling of oral drugs performance. In order to facilitate the use of PBPK modeling tools, a couple of companies have launched commercially available software such as GastroPlus™, Simcyp™ PBPK Simulator and PK-Sim®. This paper highlights various application fields of PBPK/PBBM modeling, along with the basic principles, advantages and limitations of this approach, and provides relevant examples to demonstrate the practical utility of modeling & simulation tools in different stages of formulation development.

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“…In the case of colorectal cancer (CRC), it is the fourth most commonly diagnosed and third most deadly cancer worldwide [1]. The combination of enhanced biorelevant in vitro and in silico dissolution testing could streamline the research and development process for new colon-targeted formulations [4,5]. In silico models that can simulate luminal flow inside the colon enable the investigation of colonic drug delivery systems to interpret how flow parameters can affect the breakdown of different formulations and API release [6,7].…”

Section: Introductionmentioning

confidence: 99%

Luminal Fluid Motion Inside an In Vitro Dissolution Model of the Human Ascending Colon Assessed Using Magnetic Resonance Imaging

et al. 2021

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Knowledge of luminal flow inside the human colon remains elusive, despite its importance for the design of new colon-targeted drug delivery systems and physiologically relevant in silico models of dissolution mechanics within the colon. This study uses magnetic resonance imaging (MRI) techniques to visualise, measure and differentiate between different motility patterns within an anatomically representative in vitro dissolution model of the human ascending colon: the dynamic colon model (DCM). The segmented architecture and peristalsis-like contractile activity of the DCM generated flow profiles that were distinct from compendial dissolution apparatuses. MRI enabled different motility patterns to be classified by the degree of mixing-related motion using a new tagging method. Different media viscosities could also be differentiated, which is important for an understanding of colonic pathophysiology, the conditions that a colon-targeted dosage form may be subjected to and the effectiveness of treatments. The tagged MRI data showed that the DCM effectively mimicked wall motion, luminal flow patterns and the velocities of the contents of the human ascending colon. Accurate reproduction of in vivo hydrodynamics is an essential capability for a biorelevant mechanical model of the colon to make it suitable for in vitro data generation for in vitro in vivo evaluation (IVIVE) or in vitro in vivo correlation (IVIVC). This work illustrates how the DCM provides new insight into how motion of the colonic walls may control luminal hydrodynamics, driving erosion of a dosage form and subsequent drug release, compared to traditional pharmacopeial methods.

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In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing

Cited by 21 publications

References 71 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

The emerging role of physiologically-based pharmacokinetic/biopharmaceutics modeling in formulation development

Luminal Fluid Motion Inside an In Vitro Dissolution Model of the Human Ascending Colon Assessed Using Magnetic Resonance Imaging

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